Inflammatory bowel disease (IBD) is a group of chronic, relapsing inflammatory disorders of the gastrointestinal tract. Its two principal forms are Crohn's disease and ulcerative colitis, which differ in where they occur and how deeply they penetrate the bowel wall. Current understanding holds that IBD arises from a dysregulated immune system response to the intestinal microbiota in people with genetic susceptibility, with a defective mucosal barrier playing a central role. The conditions are idiopathic and lifelong, and treatment aims to induce and maintain remission rather than to cure.
IBD matters for public health because it usually begins in young adulthood and often persists for decades, causing diarrhea, abdominal pain, bleeding, weight loss and fatigue, and sometimes serious complications such as strictures, fistulas, colectomy and an elevated risk of colorectal cancer. Its prevalence is high in Europe and North America and is rising in newly industrialized regions, which makes epidemiological and health-system questions as important as laboratory ones. The therapeutic landscape changed rapidly after the introduction of anti-TNF biologics, and it now includes cytokine-targeted antibodies, oral small molecules and experimental cell-based and microbiome-based approaches.
This entry first defines IBD and distinguishes it from related conditions, then describes the clinical and pathological features of each main form, classification, epidemiology, genetic and environmental causes, immunopathogenesis, diagnosis and treatment (medical and surgical), complications, special populations, the history of research, emerging therapies, and the open questions that remain.
Definition and scope
Inflammatory bowel disease (IBD) is a group of chronic conditions of the digestive tract in which the immune system repeatedly provokes inflammation. It is a group of conditions of the gastrointestinal tract with chronic or recurring immune response and inflammation. The cause of the group as a whole is unknown, so the conditions are described as idiopathic. Two forms account for most cases, Crohn's disease and ulcerative colitis, and they are grouped together for several reasons. Both are relapsing, both involve immune-driven mucosal injury, and both can be hard to tell apart at first presentation. Their differences lie chiefly in where the inflammation sits, how deep it reaches and what the tissue looks like under the microscope. Crohn's disease has a predilection for the ileocecum but anywhere along the gastrointestinal tract is possible, whereas ulcerative colitis traditionally arises from the rectum and can extend proximally to encompass the entire colon. The two conditions are also distinguished by the absence of a single confirmatory test: they are idiopathic inflammatory bowel diseases without a unique, gold standard diagnostic test.
Several conditions can mimic IBD, and clinicians must exclude them before the label is applied. Infectious colitis caused by enteric bacteria, viruses or parasites, including infection with Clostridioides difficile, can produce bloody diarrhea, fever and ulceration that resemble an IBD flare. Ischemic colitis results from reduced blood flow to the colon and typically affects the watershed segments. Drug-induced enterocolitis, for example from nonsteroidal anti-inflammatory drugs or certain antibiotics, and radiation enteritis or proctitis after pelvic radiotherapy also share features with IBD. These entities are separated from IBD by their history, distribution, and the findings of biopsy and histopathology.
Irritable bowel syndrome (IBS) is the condition most often confused with IBD in practice, yet the two differ fundamentally. IBS is classified as a functional gastrointestinal disorder, which means there is some type of disturbance in bowel function. Unlike IBD, IBS does not involve intestinal inflammation. In persons with IBS, the intestine appears normal upon endoscopic examination and leukocytes are not present in the mucosa or in fecal specimens. Symptoms overlap considerably, and approximately one in three patients with quiescent inflammatory bowel disease, defined as the absence of endoscopic evidence of active inflammation, experience IBS-type symptoms. Therefore, the presence of IBS-like symptoms does not exclude IBD, and objective markers of inflammation remain necessary to separate the two.
A residual group of patients cannot be placed in either main category. Such cases are labelled inflammatory bowel disease unclassified (IBD-U). Unclassified patients with overlapping features of CD and UC are termed "inflammatory bowel disease unclassified" (IBDU). The proportion is modest, with approximately 10-15% of inflammatory bowel disease (IBD) patients with overlapping features of ulcerative colitis (UC) and Crohn's disease (CD) are termed as inflammatory bowel disease unclassified (IBDU). The label is usually provisional. These are considered more as temporary diagnoses when the difference between UC and CD cannot be determined at the time of presentation. Follow-up can change the picture, since IBDU may evolve into UC or CD during follow-up, and hemorrhage was associated with CD reclassification. Small-bowel capsule endoscopy has also been used to re-examine these cases, and in one retrospective series it allowed reclassification in about one third of cases, with subsequent treatment modifications.
The older term "indeterminate colitis" has narrowed in meaning. It was introduced in 1970 for colectomy specimens with overlapping features, and it is now reserved for surgical material. The prior designation of "indeterminate colitis" is now used only after pathological assessment of a resected colon. The 2006 Montreal classification adopted the wording "inflammatory bowel disease type unclassified" for the pre-surgical setting, so that the diagnosis describes an unresolved clinical state rather than a distinct disease.
Clinical features and presentation
Core symptoms
Diarrhea, abdominal pain, rectal bleeding, urgency to defecate, fever and weight loss make up the core picture of IBD, but no single feature is universal and the mix depends on disease type and location. In ulcerative colitis (UC), diarrhea is often bloody or contains pus, and cramping and bleeding follow from the superficial inflammation of the rectum and colon. Rectal bleeding and urgency are most prominent when inflammation is confined to the rectum and left colon, because the distal bowel is the site of the most intense symptoms. Crohn's disease (CD) can involve any segment from mouth to anus, so its symptoms track the affected site. Ileal disease tends to cause right-sided pain, malabsorption, and weight loss, and it may produce relatively little diarrhea. Colonic CD resembles UC more closely, with diarrhea and bleeding. Oral ulcers are more typical of CD than UC. Systemic features such as fever, fatigue, and malaise signal more widespread inflammation and are most common in CD and in severe flares of either disease. Obstructive symptoms such as bloating, vomiting, and colicky pain point to stricturing disease, while pain, discharge, and drainage from the perianal skin suggest perianal involvement. Severe UC can present acutely with heavy bleeding, fever, and tachycardia, which requires urgent assessment.
Extraintestinal manifestations
Inflammation outside the gut, termed extraintestinal manifestations (EIMs), affects a substantial minority of patients. One cited figure is that as many as one in four people with UC experience EIMs, while a broader review reports occurrence in up to half of patients. In CD, reported prevalence ranges from 6% to 36%, depending on study design. In a European inception cohort followed for ten years, the cumulative prevalence of a first EIM was about 17%, and CD patients were roughly twice as likely as UC patients to develop one. Extensive colonic involvement in UC increased the risk relative to proctitis.
The joints, skin, eyes, and hepatobiliary system are the most frequently affected sites. Peripheral arthritis is the most common EIM, while axial involvement includes sacroiliitis and ankylosing spondylitis. Skin manifestations include erythema nodosum, pyoderma gangrenosum, and oral aphthous ulcers. Eye involvement ranges from episcleritis to uveitis. In the liver and biliary tree, primary sclerosing cholangitis is strongly associated with UC, while gallstones (linked to loss of bile acids in the ileum) and fatty liver are more general complications. Clinically, EIMs are often grouped into three categories: those that rise and fall with bowel activity, such as erythema nodosum and aphthous ulcers; those that run an independent course, such as ankylosing spondylitis and uveitis; and those whose link to the bowel is unclear, such as pyoderma gangrenosum and sclerosing cholangitis.
The mechanisms remain incompletely defined. Proposed explanations include spread or translocation of immune responses from the inflamed intestine to other organs; a separate inflammatory process that shares genetic or environmental susceptibility with IBD; and antigen mimicry, in which epitopes shared between colon, eye, joint, and bile duct epithelium may trigger cross-reactive immunity. Gut-experienced memory lymphocytes that carry homing receptors directed to both the intestine and extraintestinal tissues have also been proposed as a link, as have changes in leukocyte trafficking and alterations in the microbiota. Diagnosis is complicated by the absence of consistent criteria for EIMs and by the need to distinguish them from drug side effects and other complications.
Course, relapse and flares
IBD follows a relapsing and remitting course, with alternating periods of quiet disease and renewed activity. Flares are generally unpredictable, and the timing of an individual flare is usually difficult to foresee. Symptoms vary in severity, location, and pattern over time, and some patients have long periods without symptoms while others relapse early and often. Remission is not equivalent to cure, because inflammation can persist without obvious symptoms and can later re-emerge.
Flares may be triggered or occur without an identifiable cause. Infection, whether enteric or systemic, can activate the gut mucosal immune system and precipitate relapse. Perceived stress has been associated with a short-term increase in relapse risk in a case-crossover study that used daily diaries. Medication effects are variable: nonsteroidal anti-inflammatory drugs have context-dependent effects, antibiotics and missed doses of maintenance therapy are common precipitants, and hormonal treatments have been linked to relapse. Sleep disturbance was associated with relapse in CD but not clearly in UC in one cohort. Seasonal patterns have been proposed to reflect eosinophil activity linked to allergen exposure. Food intolerances are often reported by patients as triggers, but evidence for specific dietary triggers is inconsistent, and current guidelines do not recommend routine dietary restriction during remission. Relapse is frequently attributed to failure of maintenance therapy, and an identifiable cause is found in only some cases. Research on fecal biomarkers such as S100A12 suggests that rising levels may precede clinical relapse by several months, which could support earlier intervention, though this remains under investigation.
Repeated flares affect physical functioning, psychological well-being, work capacity, and social participation, which is why the unpredictable course is central to the burden of IBD.
Crohn's disease: pathology and patterns
Transmural inflammation and skip lesions
Crohn's disease is a chronic regional enteritis that most often involves the terminal ileum, but it can affect any segment of the gastrointestinal tract from mouth to anus (Medscape reference: Crohn disease pathology). The defining feature is inflammation that spans the full thickness of the bowel wall. The inflammation associated with CD, known as transmural inflammation, involves all layers of the bowel wall. The affected wall thickens and becomes edematous, and in long-standing disease it becomes fibrotic with fibrosis present in long-standing forms of the disease.
Involvement is discontinuous. Diseased segments alternate with stretches of apparently normal intestine, a pattern known as skip lesions segments of inflamed tissue, known as "skip lesions," are separated by apparently normal intestine. Skip lesions are easy to miss. In one retrospective cohort, 45 of 202 patients (22.3%) had endoscopic skipping proximal to TI intubation, and fifty patients (24.5%) had small bowel skip lesions, primarily in the ileum. Linear ulcers and edema in the intervening mucosa give the surface its "cobblestone" appearance. Strictures are more often found in the small intestine than in the colon, and at sites of severe inflammation the mesenteric fat can extend around the bowel, a finding termed creeping fat the mesenteric adipose tissue can expand around the intestinal segment, which is known as "fat wrapping" or "creeping fat".
Granulomas and deep ulceration
Granulomas are a histological hallmark, although they are not always present. A hallmark of CD is the presence of discrete aggregations of inflammatory cells, known as granulomas, which are generally found in the submucosa. Some cases show typical discrete granulomas, while others show a diffuse granulomatous reaction or a nonspecific transmural inflammation. Because the granulomas are not universal, their absence does not exclude the disease the absence of granulomas also is consistent with the disease. The granulomas are non-necrotizing and are composed of epithelioid histiocytes in some cases, by non-necrotizing granulomas composed of epithelioid histiocytes.
Ulceration can be deep. Resection specimens may show mural microabscesses, serositis, and ulceration that reaches at least the muscularis propria mural microabscess formation, serositis, deep ulceration (at least through the muscularis propria). When transmural damage progresses, the wall can give way. Fissures, fistulas and abscesses can develop, and fistulas may connect the bowel with other organs, including the bladder and the skin Chronic transmural inflammation can lead to fissures in the bowel wall with ensuing fistulas and abscesses. Fistulas may develop between the bowel and other organs, including enteroenteric, enterogastric, enterovaginal, enterocutaneous, and enterovesical fistulas.
Disease behaviour
Crohn's disease behaviour is classified into three patterns: inflammatory, stricturing, and penetrating. The Montreal classification, published in 2005 as an update of the Vienna system, codes these as B1, B2 and B3 Inflammatory, non-stricturing, non-penetrating disease; Stricturing disease; Penetrating disease. Stricturing disease results from fibrosis: the persistent and chronic inflammation results in fibrosis and subsequent luminal narrowing, which poses difficulty for the passage of enteric contents. Penetrating disease reflects full-thickness injury, in which persistent and chronic transmural inflammation results in the development of a sinus or fistulous tract with or without abscess.
At diagnosis, most patients show the inflammatory pattern. In one prospective cohort of 179 patients, behavior at presentation: inflammatory 62.0%, stricturing 24.6%, penetrating 13.4%, and by the end of follow-up the proportion with stricturing or penetrating disease had risen behavior at follow-up period end: inflammatory 43.6%, stricturing 38.0%, penetrating 18.4%. The classic model treats the hierarchy as one-way, but this has been challenged. A bidirectional version that accounts for regression found that 90% of patients exhibited inflammatory disease behavior at 5 years, compared to 58% if the hierarchical, unidirectional Montreal classification system was implemented.
Perianal disease
Perianal involvement is a distinct and common feature. The Montreal system records it as a separate modifier, p, rather than as a behaviour category Perianal disease. Estimates vary by source; one trial description notes that perianal Crohn's disease (pCD) affects around one-third of patients with Crohn's disease (CD) during their disease course. Risk depends strongly on location. Perianal fistulae have been reported in 12% of subjects with small intestinal CD, 15% with ileocolonic CD, 41% with colonic CD without rectal involvement and 92% of those with colonic CD with rectal involvement.
Perianal disease takes several forms, including fistulas with multiple external openings, abscesses, and deep anal ulcers. Complex fistulas may pass through the sphincter complex and extend well beyond the perineum. Patients with perianal disease tend to have a harder disease course, and the presence of perianal disease portends poor outcomes in CD and can substantially compromise quality of life. Management is typically multidisciplinary. Drainage comes first: drainage of an abscess and possible seton placement to prevent future septic complications is the critical first step. Medication is then added, and anti-TNF agents have the strongest evidence for healing fistulas TNF inhibitors (TNFi) have the best evidence for decreasing perianal drainage and fistula healing.. Results remain limited: medical therapy with anti-TNF could only achieve prolonged remission in 30-40% of pCD cases. At the same time, surgical treatment could only lead to a favourable outcome in around 50% of patients, which is why combined medical and surgical strategies are increasingly favoured.
Ulcerative colitis: pathology and extent
Ulcerative colitis is largely a disease of the colonic lining. Its inflammation is superficial, mostly transmucosal, and only sometimes reaches the submucosa, which contrasts with the full-thickness pattern seen in Crohn's disease (Crohn's disease). The process is typically diffuse, usually beginning at the lowest part of the rectum and extending a variable distance upward. The rectum is involved in almost every case [19-6], and the inflammation then climbs the colon as an unbroken band [1-3]. Exceptions do occur. Some patients with proctitis or left-sided disease show a caecal patch of inflammation, and rectal sparing is occasionally seen [1-7]. These atypical patterns can lead to misclassification, and they are most often noticed in biopsy or resection specimens [11-1, 11-2].
Disease extent is described by how far proximally the inflammation reaches. The Montreal scheme labels proctitis as E1, left-sided colitis as E2, and extensive colitis or pancolitis as E3 [8-3]. Proctitis is confined to the rectum [6-5], proctosigmoiditis involves the rectum and sigmoid colon [6-6], and left-sided colitis extends as far as the splenic flexure [6-7]. Pancolitis affects the entire colon [6-8]. A rare, severe form called fulminant colitis is a particular type of pancolitis, and it can bring dehydration, bleeding and even shock [6-9, 6-10]. Most people are diagnosed with rectal-limited inflammation, while about 20 percent have pancolitis [9-4, 9-5]. Extent matters because it determines treatment. Proctitis and left-sided disease can be treated with rectal enemas or foams, whereas pancolitis generally requires oral medication so that the drug reaches the whole colon [6-12]. Extent also predicts outcome: patients whose inflammation is confined to the rectum and a short adjacent segment usually have milder symptoms and a better prognosis [3-8]. Extent can change over time. One clinical education resource reports that up to 20 percent of patients show extension within five years [9-8]. Children more often present with extensive disease than adults do [10-1].
Histology is central to establishing the diagnosis. The European consensus describes the microscopic diagnosis as resting on widespread crypt architectural distortion, a diffuse transmucosal infiltrate with basal plasmacytosis, and, in active disease, cryptitis and crypt abscesses [10-3]. Distortion is found in 57–100% of UC cases, compared with 27–71% in Crohn's disease, and the crypts may appear branched, dilated, shortened or irregularly spaced [12-5, 12-11]. Chronicity is defined by features such as basal lymphoplasmacytosis, crypt distortion and, in the left colon, Paneth cell metaplasia [11-2, 12-9]. Granulomas are typically absent in UC unless crypts have ruptured [14-7]. Endoscopically, the mucosa often shows loss of the normal vascular pattern, erythema, friability and superficial ulceration, sometimes with pseudopolyps [19-5].
Distinguishing UC from its mimics depends on these features. Acute infectious colitis usually shows evidence of acute colitis but typically lacks features of chronicity such as architectural distortion and basal lymphoplasmacytosis, which is why chronicity is considered reliable [11-9]. Other conditions can also produce crypt distortion. Amoebic colitis can resemble chronic active UC [13-6], and mycophenolate-associated injury can mimic it through significant architectural change [13-7]. Diagnosis is harder in early disease, when crypt architecture may still be preserved. Mild ileal inflammation, known as backwash ileitis, is common and does not exclude a diagnosis of UC. When biopsies remain indeterminate, the clinical course is often used to guide treatment [2-7].
Disease duration changes the histological picture, and it is also the main driver of colorectal cancer risk. In long-standing disease, widespread architectural crypt distortion and increased cellularity of the lamina propria make the diagnosis more obvious. Risk rises with time: classic estimates suggested roughly 2% after 10 years, 8% after 20 years and 18% after 30 years of disease, although more recent cohorts report lower figures, around 7% at 30 years [23-5]. Extent, primary sclerosing cholangitis, family history, and the severity of histological inflammation are also recognised risk factors [28-4]. Surveillance is generally started 8–10 years after onset in patients whose colitis extends beyond the rectum, and the colorectal cancer risk is considered in relation to these thresholds [22-7].
Classification and disease assessment
Classification in IBD serves two purposes: recording a patient's disease phenotype (its location and behaviour) and measuring its current activity. Research and trials rely on the first for standardized description and on the second for endpoints.
The Montreal classification
The Montreal classification, developed in 2005 as a revision of the Vienna classification, is the most widely used system for Crohn's disease. For Crohn's disease it codes three axes. Age at diagnosis is A1 (16 years or younger), A2 (17–40) or A3 (over 40). Location is L1 (ileal), L2 (colonic), L3 (ileocolonic) or L4 (upper gastrointestinal), and L4 can be added to the other codes as a modifier. Behaviour is B1 (non-stricturing, non-penetrating), B2 (stricturing) or B3 (penetrating), with a lowercase p appended for perianal disease. For ulcerative colitis the scheme codes extent (E1–E3) and severity (S0–S3).
Several rules limit how the code is read. Disease behavior is considered permanent unless progression occurs, and it is recommended to determine it no earlier than 5 years post-diagnosis. The B1 label is provisional until a prespecified interval has passed, commonly 5–10 years. The code can remain stable while inflammation improves, and the behavior portion can change as complications develop. It is therefore a descriptor and not a measure of activity. The pediatric Paris modification adds finer age bands (A1a under 10 years, A1b 10 to under 17) and splits upper disease into L4a and L4b, because the original scheme does not capture the dynamic features of pediatric disease phenotype (change in disease location and behavior over time, growth failure).
Activity indices
Activity is measured with separate scores. For Crohn's disease, the Crohn's Disease Activity Index is the usual trial measure. A score below 150 is treated as remission, and a response is commonly defined as a fall of at least 70 points and at least 25% from baseline. For ulcerative colitis, the Mayo score is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, physician's global assessment, and endoscopy findings) and ranges from 0 to 12 points. The partial Mayo score omits the endoscopic component. Regulators have tightened the definition of remission: FDA guidance recommends that the endoscopy subscore be 0 or 1 (modified), with mild friability excluded, and it notes that the physician's global assessment is a key limitation because a single general item cannot fully capture symptoms.
Endoscopic scoring is more granular. The Simple Endoscopic Score for Crohn's Disease grades ulcer size, ulcerated surface, affected surface and narrowing at five sites, and protocols report the total as 0 to 56, while others state 0–60; the discrepancy reflects differing site counts and should be checked against each protocol. In ulcerative colitis, the Mayo endoscopic subscore is the most widely used endoscopic index for assessment of UC disease activity, alongside the UCEIS and DUBLIN scores. In a retrospective cohort of 74 patients treated with vedolizumab, the post-treatment UCEIS best predicted later surgery or treatment escalation, with an area under the curve of 0.871 (area under curve of 0.871), although this single-centre study is limited in size.
Use in trials and daily practice
Trials use these instruments to define remission and response, which is why their precise thresholds matter for comparing drugs. In routine care, shorter tools such as the Harvey-Bradshaw index are common for Crohn's disease, and clinicians combine symptoms with endoscopy, biomarkers and imaging rather than relying on any single number.
Phenotype and prognosis
Phenotype is the disease's classified form at a given time and is used to predict course. Early age at diagnosis, fibro-stenotic or penetrating disease behavior and involvement of the proximal small bowel have been associated with later complications and intestinal resection. Because phenotype is not the same as activity, a patient with a given code may be in deep remission or having a severe flare, and phenotype is most useful when combined with activity measures to decide how intensive therapy should be.
Epidemiology and global distribution
Prevalence in Europe and North America
Crohn's disease and ulcerative colitis have been recorded most often in northern Europe, the United Kingdom and North America, which were the first regions to report large case series. Still, the figures vary by source. The highest reported annual prevalence in North America is 249 per 100,000 persons for ulcerative colitis and 319 per 100,000 for Crohn's disease. In Europe the corresponding peaks are 505 per 100,000 for ulcerative colitis and 322 per 100,000 for Crohn's disease . These values come from a systematic review of studies published up to 2012, and they represent the upper end of the reported range rather than typical national averages. Crude totals are often given instead: one European review estimated 2.5–3 million people in Europe with IBD, while a North American estimate placed prevalence at about 0.5% of the population, with a projection of roughly 4 million cases by 2030 .
Incidence and prevalence are not moving in the same direction. Since 1990, most population-based studies from Western countries have reported stable or falling incidence for both diseases, yet prevalence remains above 0.3% in North America, Oceania and most of Europe . Because patients with long-standing disease stay in the count, a stable incidence can still produce growing prevalence. Canadian data illustrate the point: the national population with IBD is expected to rise substantially by 2030 .
Age and sex at onset
The disease is most often diagnosed in young adults. Crohn's disease is usually diagnosed between ages 18 and 35, with a second, smaller peak between about 50 and 60 . Ulcerative colitis has no consistent sex difference in incidence until about age 45, after which men have a higher incidence . Onset in childhood and adolescence is also recognised, and early-onset Crohn's disease, defined as before age 16, has been reported more often in males (about 20% versus 12% of cases in one series) . Whether paediatric onset is becoming more common is contested. A Swiss cohort found that the age at onset had risen over time, which does not support the view that patients are being diagnosed at younger ages .
At the other end of life, elderly-onset disease, usually defined as onset after age 60 or 65, is increasingly recognised. One global analysis estimated that it accounts for about 13% of all cases, and that it is more common in men in rising trends . Sex differences in Crohn's disease depend on age and region. In a pooled analysis of Western cohorts, women had a lower risk of Crohn's disease until ages 10–14 and a higher risk thereafter . In the Asia-Pacific region, by contrast, men had a higher incidence of Crohn's disease from early adolescence to about age 50 .
Rising incidence in newly industrialized regions
Although IBD was long regarded as a disease of Western countries, incidence has risen sharply in newly industrialized regions of Asia, Latin America and Africa since about 2000 . Within these regions, the increase appears to follow economic development. In Brazil, for example, the prevalence in the economically advanced and densely populated São Paulo was about three times that in the poorer state of Piauí in 2020 . Japan's prevalence roughly doubled between 2000 and 2016 , while China, which industrialized later, reported an incidence of 10.04 per 100,000 person-years in 2016 .
Two explanations have been offered for this shift. The first is that economic growth improves awareness and access to health care, which reveals cases that were previously undiagnosed; the second is that Westernisation of diet and environment genuinely increases the number of people who develop the disease. Evidence supports the second explanation as well as the first . The proposed environmental drivers include changes in diet, reduced microbial exposure in early life, greater antibiotic use and pollution . Researchers also argue that the Westernisation of diets and environments affects the intestinal microbiome, thereby raising risk in people who are genetically susceptible . Genetic change cannot account for the pattern on its own, because the rise has occurred too quickly and varies within populations of similar genetic background . The specific exposures involved, and whether those prevalent in the West act in the same way in Asia, remain under investigation .
Genetic susceptibility
Family clustering was the first strong evidence that inherited factors shape IBD. Sibling risk ratios are estimated at about 15 to 42 for Crohn's disease and 7 to 17 for ulcerative colitis. Twin studies refined this picture. In a Swedish nationwide cohort of 111,080 twins, the proband concordance for Crohn's disease was 0.30 in monozygotic pairs and 0.02 in dizygotic pairs, while the corresponding figures for ulcerative colitis were 0.15 and 0.03. Model-based estimates from the same cohort put heritability at 0.78 for Crohn's disease and 0.57 for ulcerative colitis, which supports the view that the genetic contribution is substantially stronger in Crohn's disease. Other series report higher concordance, with figures of up to about 50% in identical twins for Crohn's disease and up to 15% for ulcerative colitis, so the exact values depend on the cohort and the length of follow-up. Early segregation analyses had already proposed different inheritance patterns, a dominant or additive gene with low penetrance for ulcerative colitis and a recessive gene with high penetrance for Crohn's disease, though these models are now considered simplistic. Even in identical twins, concordance never approaches 100% in published series, which indicates that non-genetic or epigenetic factors must also contribute.
The first susceptibility gene, NOD2 (CARD15), was identified in 2001 within a linkage region on chromosome 16, and this discovery redirected research toward innate immune sensing and barrier function. Subsequent genome-wide association studies (GWAS) identified further loci, including ATG16L1 and IL23R. Studies now report more than 240 susceptibility loci. Most associated variants are noncoding and sit in strong linkage disequilibrium with neighboring genes, so the causal variant is often unclear, although fine-mapping has directly implicated NOD2, IL23R, ATG16L1 and PTPN22. The functional picture centers on innate immune bacterial sensing and autophagy. NOD2 is an intracellular pattern-recognition receptor, and its variants carry the largest share of Crohn's disease risk among the loci known at the time. NOD2 can also induce autophagy and physically interacts with ATG16L1 to clear intracellular pathogens. Epithelial cells and dendritic cells that carry Crohn's-associated ATG16L1 or NOD2 variants show defective antibacterial autophagy, and in dendritic cells this impairs the presentation of exogenous antigens to CD4+ T cells.
The risk loci also point to shared immune biology beyond the bowel. Almost three-quarters of IBD genetic risk loci overlap with those of other immune-mediated diseases. Pathway analyses repeatedly highlight NF-κB signaling, JAK-STAT signaling and cytokine–cytokine receptor interaction. Shared biology does not mean identical genetics: the two main subtypes have a genetic correlation of about 0.54, which is compatible with substantial distinct components.
Genetic findings have been used to define clinically relevant subgroups and to nominate drug targets. Pediatric-onset disease accounts for at least a quarter of IBD diagnoses and often involves stricturing, perianal disease and poor response to conventional treatment, and NOD2 is the most replicated adult locus. Genetic data have also shown pharmacological relevance: one GWAS found that carriage of the HLA-DQA1*05 allele, present in roughly 40% of Europeans, doubled the risk of immunogenicity to anti-TNF therapy. Causal inference approaches such as Mendelian randomization, combined with druggable-gene databases, have nominated candidates including RORC, TNFRSF25 and THBS3, although these remain at the level of genetic prioritization rather than clinical validation.
Genetics still leaves much unexplained. GWAS hits account for only about a tenth of susceptibility by one estimate. Rare variants with larger effects have been proposed as part of the gap, but this remains a hypothesis. Possible explanations for missing heritability include oversimplified models of genetic identity, unmeasured environmental influences and the neglect of epigenetic effects. Gene–environment interaction, which connects this section to the environmental and microbial factors discussed elsewhere, is therefore central to interpreting the risk loci. Despite the size of the gene catalogue, a substantial effect of genetic risk assessment on treatment decisions and disease outcome has not yet been demonstrated.
Environmental factors and the gut microbiota
Lifestyle and exposure risk factors
Environmental influences seem to operate at different ages. Breastfeeding, antibiotic use in the first year of life, contact with livestock and pets, sibling number and population density are thought to affect later risk, possibly by shaping the developing intestinal microbiome, while lifestyle factors gain weight in adulthood.
Tobacco has the most clearly directional effect. Smoking raises the likelihood of Crohn's disease and worsens its course, whereas in ulcerative colitis it appears to be protective: tobacco use acts as a protective factor against flare-ups in patients with UC. Stopping may carry its own risk in colitis, since some reports describe a flare following cessation. Proposed mechanisms include changes to immune responses and the composition of the gut microbiome, along with altered integrity of the epithelial mucous membrane.
Diet is harder to pin down. Reviews associate a high intake of fruits, vegetables, and fiber with lower risk and a Western dietary pattern with higher risk, yet because ingested food, host microbiome, and immune function interact in a complex manner, it is difficult to determine whether a single food component is a direct cause of IBD. Ultra-processed foods appear among the adverse factors in large evidence reviews. Antibiotic exposure is another recurring signal: one summary table lists an odds ratio of about 1.8 for prenatal antibiotic exposure. Urban life also features, with one Spanish case-control study identifying living in an urban environment among its main risk factors, alongside high intakes of protein, carbohydrate and fat. Interventional evidence is thin, since interventional or randomized controlled studies evaluating the efficacy of modifying environmental risk factors remain limited and mostly focus on dietary intervention.
Dysbiosis and the problem of causality
Patients consistently show a microbial community that differs from that of healthy people. Dysbiosis, characterized by reduced microbial diversity and altered composition, is a hallmark of IBD. Among the most reproducible changes are a reduction in the diversity of gut microbiota and the lower abundance of Firmicutes. At the species level, a consistent decrease in anti-inflammatory bacteria, such as Faecalibacterium prausnitzii, and an increase in pro-inflammatory species, including Escherichia coli, have been observed. Functional consequences follow, with decreased short-chain fatty acids (SCFAs) and secondary bile acids reported in metabolomic studies.
The pattern varies by disease. Diversity loss is more prevalent in CD than UC, and one study found a decrease in bacterial diversity in IBD patients with ileal disease but no decreased diversity in IBD patients with the colonic disease. Loss of diversity also tracks disease course, since as the disease progressed through different stages, the diversity of the bacteria decreased.
Whether dysbiosis drives disease or results from it remains unresolved. Early-onset cohorts are informative here: this reduction in diversity has been shown to occur early in the course of Crohn's disease in a pediatric population, suggesting that the dysbiosis may not only be an effect of IBD but also contribute to ongoing pathogenesis. Even so, reviews conclude that while dysbiosis is thought to be a feature of IBD, its exact role in pathogenesis is unclear. Medication, diet, hospital care and the inflamed bowel itself all reshape the microbiota, so cross-sectional comparisons cannot by themselves establish direction.
Pathogens and enteric infections
Infection has long been proposed as a trigger, but no single agent has been confirmed. One review noted that recent reports in the literature do not suggest that a specific persistent infection causes IBD, but indicate that enteric pathogens could cause initial onset of IBD and are associated with reactivation of quiescent disease. This has been framed as a "hit-and-run" model, in which self-limited infections initiate a cascade of inflammatory events leading to chronic, relapsing disease in a genetically susceptible host. Some authors instead argue that commensal enteric bacteria and their products are the "triggers" that initiate and perpetuate IBD.
Evidence for a role comes mainly from population registers. A Swedish national study found that previous episodes of gastroenteritis increased the odds of later IBD, and the authors suggested that enteric infections might induce microbial dysbiosis that contributes to the development of IBD in susceptible individuals, while acknowledging possible misclassification. A systematic synthesis found that among population-based studies of gastroenteritis, the presence of bacteria including the Salmonella species, Campylobacter species, and Clostridioides difficile demonstrated positive associations with the development of incident IBD. Seasonal analyses point in the same direction: the similarity in the time trends of Crohn's disease, ulcerative colitis, and bacterial intestinal infections suggests that superinfection by intestinal bacteria may drive short-term fluctuations in admissions, whereas viral infections showed different seasonal variations that showed no relationship with any of the fluctuations of inflammatory bowel disease.
Evidence against a simple causal role is also substantial. In a prospective cohort of patients with symptomatic flares, non-Clostridium difficile enteric infections were identified in 17% of symptomatic patients with IBD, and endoscopic and histologic findings may not differentiate flare from infection. Detection itself is problematic, and infections may be understated, due to the problems in detecting enteric pathogens. Viral agents such as norovirus remain under-characterized, although genetic associations involving the FUT2 and FUT3 genes link host glycan biology to viral binding sites.
Immunopathogenesis
Current models place the origin of IBD in a misdirected immune reaction to luminal material, arising in people with inherited susceptibility. Pathogenesis is described as an aberrant response to gut luminal antigen in a genetically susceptible host. The two main forms overlap genetically, yet their dominant T-cell programs differ, and they are characterized by very different T cell responses. The sections below follow the chain from barrier breach to innate sensing, adaptive polarization, and cytokine-driven tissue injury.
Epithelial barrier and mucus
The intestinal epithelium is a single cell layer that, together with a mucus gel and secreted antimicrobial peptides, keeps bacteria and other luminal material at a distance from the lamina propria. In IBD this barrier is weakened in several ways. Goblet cells produce a thinner and less protective mucus layer, Paneth cells in the terminal ileum of patients with Crohn's disease secrete reduced amounts of defensins, and epithelial cells undergo increased apoptosis, which increases mucosal permeability. Such exposure lets antigens reach immune cells that are normally kept in check. Genetic work supports this: a number of genes involved in intestinal epithelial cell function are genetically associated with IBD. Cytokines also shape the barrier itself. In a mouse colitis model, IL-17A acts on intestinal epithelium to promote barrier function, and blocking it aggravated colitis, which suggests that the barrier defect can be worsened by specific immune interventions as well as by the disease itself.
Innate immune cells
Innate cells detect microbial molecules and then direct adaptive responses. Antigen-presenting cells produce IL-12, IL-23, and IL-27 during antigen presentation to naïve T cells, so macrophages and dendritic cells set the cytokine tone of the mucosa. Dendritic cells are also a point of microbe-specific activation. Adherent-invasive <i>Escherichia coli</i> triggers more IL-23 release from dendritic cells of patients with Crohn's disease than from those with ulcerative colitis, and this strain resists antimicrobial peptides and persists within macrophages. AIEC strains are highly virulent, with high resistance to antimicrobial peptides and a strong ability to persist within macrophages. Neutrophils accumulate in the inflamed mucosa, where they can feed back on the inflammatory loop. Activated neutrophils may prompt a positive feedback producing IL17A and IL22.
T cells and B cells
In Crohn's disease, the CD4 T-cell response is dominated by Th1 and Th17 programs. IL-12 is the major inducer of Th1 cells producing IFN-γ via direct interaction with IL-12 receptors on undifferentiated T cells, whereas TGF-β and IL-6 are the main inducers of Th17 cells, and IL-23 acts on Th17 cells that have already differentiated. IL-23 supports a distinct IL-17-producing lineage through pathways separate from the Th1 and Th2 signaling routes. IL-23 promotes the development of an IL-17 producing CD4+ helper T cell subset through mechanisms that are distinct from the Th1 (STAT1, STAT4, and T-bet) and Th2 (STAT6) pathways. Cells co-producing IFN-γ and IL-17 are enriched in inflamed mucosa in both diseases. Th17-derived IFN-γ has been shown to increase epithelial barrier permeability.
Ulcerative colitis shows a different emphasis. UC is characterized by an aberrant Th2 response with excess IL-5 and IL-13, and this disproportionately affects the colon. Natural killer T cells have also been implicated in this pattern.
Regulatory T cells normally restrain these responses, and their function is impaired in IBD. In mice, IL-23 inhibition enhances regulatory T cell accumulation, thereby dampening inflammation. B cells and plasma cells contribute through antibody production, including antibodies against microbial antigens such as anti-Saccharomyces cerevisiae antibodies, which are more frequent in Crohn's disease, and perinuclear ANCA, which is more frequent in ulcerative colitis. Whether these antibodies drive disease or merely reflect it remains unresolved, and B-cell-directed therapies have not yet produced established benefit.
Cytokine pathways
TNF is a central mediator, and anti-TNF therapy is among the most effective treatments. Its effects extend upstream: the inhibition of TNF reduced IL-12 and IL-23 secretion by macrophages, which places TNF inside the IL-12/IL-23 loop rather than beside it. IL-12 and IL-23 share the p40 subunit, they both belong to the interleukin 12 family and are related by sharing the subunit p40. IL-23 is further defined by its p19 subunit. Serum IL-23 levels in IBD are reported to be higher than in healthy people, with the highest values in patients with Crohn's disease and in those with IBD-associated arthritis.
IL-6 contributes to Th17 differentiation together with TGF-β, and its downstream signal runs through STAT3. STAT3 activation is not restricted to IL-23, because other cytokines such as IL-6, IL-21, IL-10, or IL-27 also induce STAT3 activation, and in some cases this has anti-inflammatory effects. TL1A, produced by lamina propria macrophages, has also been reported to induce Th1 and Th17 responses in cooperation with IL-23 in patients with Crohn's disease.
Sustained cytokine output damages tissue. IL-23 promotes upregulation of the matrix metalloproteinase MMP9, increases angiogenesis and reduces CD8+ T-cell infiltration. Through these and related routes, persistent signaling erodes the epithelium and drives fibrosis, which underlies stricturing disease. The relative roles of these pathways remain debated. IL-17 and IL-23 are potent inflammatory cytokines, yet their inhibition induced opposing effects in Crohn's disease clinical trials.
Diagnosis and monitoring
Diagnostic approach
No single investigation confirms inflammatory bowel disease or separates Crohn's disease from ulcerative colitis. A unique, gold standard test for IBD diagnosis is currently unavailable. Instead, the work-up draws on the history and examination, laboratory studies, endoscopy, histology and imaging. Because the symptoms of IBD, including abdominal pain, diarrhea, rectal bleeding and weight loss, are not specific to IBD, so a single technique is often insufficient for the diagnosis.
Ileocolonoscopy remains the reference investigation once IBD is suspected. It is considered the gold standard when IBD is suspected on the basis of clinical symptoms, laboratory findings and imaging. The European guideline for initial assessment recommends ileocolonoscopy with biopsies along with intestinal ultrasound, magnetic resonance enterography, or both. Sampling is taken from the terminal ileum and from each colonic segment, which allows the extent of disease to be mapped. Biopsies are best obtained before treatment starts, as treatment interventions can potentially alter the mucosal morphology. Histology is also central to separating IBD from infectious and other mimicking colitides, since endoscopic biopsy plays a pivotal role in distinguishing IBD from other conditions. Where Crohn's disease is suspected, an upper gastrointestinal biopsy is additionally suggested. When the small bowel cannot be reached by ileocolonoscopy, device-assisted enteroscopy or small-bowel capsule endoscopy is used, and push enteroscopy is recommended where capsule study and small-bowel imaging are not feasible or inconclusive. Cross-sectional imaging supplies information that endoscopy cannot, particularly for the small intestine. Among these, US is noninvasive and easily utilized, making its use highly practical in daily clinical practice.
Stool testing for enteric pathogens is routinely performed to exclude infection before the diagnosis is accepted, because infectious colitis can mimic both major forms.
Fecal biomarkers and monitoring
Fecal calprotectin is the most widely used stool marker. Calprotectin is a calcium and zinc-binding protein formed by a heteromeric complex of two subunits, S100A8 and S100A9, and it is released mainly by neutrophils and monocytes, so higher stool concentrations reflect intestinal inflammation. Its main diagnostic value is in exclusion and triage: it allows the monitoring of intestinal inflammation with a high negative predictive value, making it possible to exclude the diagnosis of inflammatory bowel disease for symptomatic patients, and it shows high sensitivity for the identification of patients requiring additional examinations for diagnosis, such as colonoscopy.
Its limits are substantial. In small-bowel Crohn's disease, stool calprotectin levels are highly variable and not specific enough for diagnosis. In a comparison of kits, fecal calprotectin discriminated IBD from irritable bowel syndrome reasonably well but performed poorly against other colitides, with specificity of about 40% in that cohort. Thresholds are also imprecise: the values that correspond to mucosal healing in ulcerative colitis ranged from 13.9 to 251 μg/g across studies, although the most common values were between 150 and 250 μg/g. A value below 150 μg/g in symptomatic remission may rule out active inflammation and spare routine endoscopy, while results in the range of 100-250 μg/g are harder to interpret and usually need confirmation by another method. A 2023-era meta-analysis suggested that 152 μg/g was an appropriate threshold for monitoring, with higher values warranting warning of relapse within 24 months. Serum markers have a narrower role: CRP and ESR are useful to confirm ongoing mucosal inflammation but are of less value to predict a future relapse.
Endoscopy remains the reference for mucosal assessment, but it is relatively expensive and invasive in routine practice, and patients often find it the least acceptable form of monitoring. For this reason, guidance such as the American Gastroenterological Association recommendation to check fecal calprotectin every 6–12 months in asymptomatic ulcerative colitis has been adopted. Histological assessment of biopsies still provides the detail needed to judge remission beyond what stool tests can show.
Diagnostic difficulty and indeterminate disease
Establishing a definitive diagnosis can take considerable time. A recent US study found an average delay of 9.5 months from symptoms to diagnosis for Crohn's disease and 3.1 months for ulcerative colitis. Delays arise because IBD can present atypically or overlap with other disease processes. Attempts to standardize the measurement have also been hampered, since there is no universally agreed definition of delay in IBDs.
Some patients cannot be classified at the first assessment. In 4–10% of cases, UC and Crohn's colitis cannot be distinguished. For chronic colitis in patients who have not had surgery, the term IBD-unclassified is applied, which is not the same as indeterminate colitis, a term reserved for colectomy specimens. Reasons for uncertainty include fulminant presentations, rectal sparing, segmental or patchy colitis, limited biopsies, equivocal histopathological features or treatment-modified features. Many cases resolve over time: in one European population-based cohort, 25% of patients were reclassified within 5 years, most often as UC (71%), with a median time to reclassification of 6 months. A minority persist, with approximately 20–60 % retain the diagnosis of indeterminate colitis over periods as long as 5–10 years. Pathologists also caution that a diagnosis of IC should never be made clinically, or in pre-resection mucosal biopsies.
Principles of medical treatment
Treatment goals and the treat-to-target approach
Medical management of IBD has moved from relieving symptoms toward controlling the underlying inflammation. The first goal is induction of remission, usually within weeks to months of a flare. The second is maintenance, meaning that remission is sustained over years. In recent practice, a third goal has gained weight: mucosal healing, judged endoscopically, and in some settings histologically. Treat-to-target strategies set explicit, measurable endpoints and adjust therapy until they are met, rather than reacting to symptoms alone. The International Organisation for the Study of IBD published STRIDE targets in 2015, updated as STRIDE-II in 2021, which combine clinical, biomarker and endoscopic endpoints with approximate timeframes. Observational data suggest that mucosal healing is associated with fewer relapses, hospitalizations and operations, although prospective validation of mucosal healing as a formal target is still incomplete. Definitions also vary: in ulcerative colitis, a Mayo endoscopic subscore of 0 or 1 is commonly used, and in Crohn's disease, normal-appearing macroscopic mucosa is the usual benchmark. Biomarker normalization, especially of fecal calprotectin and C-reactive protein, is used as a supporting measure.
Aminosalicylates
Aminosalicylates (5-aminosalicylic acid preparations such as mesalazine, and older sulfasalazine) are the classic first-line drugs for mild-to-moderate ulcerative colitis, and they are used for maintenance of remission in that disease. Their effect is largely local, acting on the colonic mucosa, which explains why they are most useful in disease confined to the colon and much less effective in Crohn's disease. Formulations are chosen to release the drug at the appropriate site, and oral and rectal forms can be combined for distal disease.
Corticosteroids
Corticosteroids remain the most rapid agents for inducing remission in moderate-to-severe flares. Systemic prednisolone or intravenous methylprednisolone is used for severe ulcerative colitis and for Crohn's disease that is not responsive to milder measures, while budesonide, which is largely cleared by the liver, is used for mild-to-moderate ileal and right-sided disease with fewer systemic effects. Steroids are not appropriate for long-term maintenance. Their adverse effects include infection, bone loss, weight gain, hyperglycemia, cataract, and mood disturbance, and dependence on them is itself a marker of poor control. For this reason, the goal is to taper steroids once remission is achieved and to replace them with steroid-sparing maintenance drugs. In severe acute colitis that does not respond to intravenous steroids, rescue with ciclosporin or infliximab, or colectomy, may be considered.
Immunomodulators: thiopurines and methotrexate
Thiopurines, namely azathioprine and its metabolite mercaptopurine, are the principal immunomodulators. They take three to six months to reach full effect, so they are used mainly for steroid-sparing maintenance rather than rescue. They are more effective at maintaining remission in ulcerative colitis than in Crohn's disease, and withdrawal is associated with relapse in a considerable share of patients. Genotyping for thiopurine methyltransferase and NUDT15 variants reduces the risk of severe myelosuppression, and dose monitoring is used to avoid toxicity. Long-term risks include lymphoma and skin cancers, so continued use is weighed against benefit. Methotrexate is given weekly, usually by injection, and is a second-line option when thiopurines fail or are not tolerated. Recent guidance supports parenteral methotrexate for moderate-to-severe Crohn's disease, particularly with a tapering corticosteroid course, while methotrexate is contraindicated in pregnancy.
Stepping therapy up or down
Traditionally, treatment followed a step-up model: aminosalicylates or steroids first, then immunomodulators, and biologics only for refractory disease. This model has been challenged by evidence that early use of more effective agents yields better mucosal healing and steroid-free remission. Decisions are guided by disease severity, extent (for ulcerative colitis) and location and behaviour (for Crohn's disease), as well as prognostic markers such as young age at diagnosis, extensive disease, perianal involvement, early steroid requirement, and deep ulceration. Patients with a favourable profile may be stepped down, with therapy de-escalated or withdrawn after sustained deep remission, while those with adverse features may be started on more intensive treatment early.
Nutritional therapy
Exclusive enteral nutrition, in which a formula is the sole source of nourishment for several weeks, is established as a first-line induction therapy for children with Crohn's disease. In adults, its role is less settled. A 2026 meta-analysis of 40 studies reported that clinical remission rates were around 66% in real-world cohorts, but corticosteroids achieved higher remission rates than enteral nutrition in randomized trials. Adherence is a practical limitation, which has led to interest in partial enteral nutrition, where some food is permitted. Nutritional support is also important for correcting deficiencies and for preoperative optimization.
Biologics and small-molecule therapies
Anti-TNF agents and anti-integrin therapy
Anti-TNF antibodies, including infliximab, adalimumab and golimumab (the last licensed for ulcerative colitis but not Crohn's disease in Europe, per the source's stated approvals), neutralize tumour necrosis factor alpha, a cytokine that drives intestinal inflammation. They have been the reference point for biologic therapy since the late 1990s. They reliably induce and maintain remission, and they are also used for mucosal healing and fistula closure. Their limitations are substantial: a meaningful minority of patients never respond, and many lose response over time, with reported rates of primary non-response and secondary loss of response that vary widely across studies. Serious infection and other systemic immunosuppressive effects also constrain their use.
Vedolizumab is a humanized monoclonal antibody against the α4β7 integrin. It blocks the binding of this integrin on gut-homing lymphocytes to MAdCAM-1 on intestinal endothelium, so that T cells and other lymphocytes cannot enter inflamed gut tissue. Because its target is largely confined to the intestine, it avoids the broad systemic suppression of TNF blockade. Vedolizumab is approved for moderate-to-severe ulcerative colitis and Crohn's disease, and it is often chosen when patients have failed or become intolerant of anti-TNF therapy. Natalizumab, which blocks the α4 integrin more broadly, works through a related mechanism but carries a significant risk of progressive multifocal leukoencephalopathy, which restricts its use in IBD. Vedolizumab's onset of action is slower than that of anti-TNF drugs, a difference that shapes sequencing decisions in acute severe disease.
IL-12/23 and IL-23 inhibitors
Ustekinumab targets the p40 subunit shared by IL-12 and IL-23, and it was the first of this group to be used in IBD. Subsequent agents act specifically on the p19 subunit unique to IL-23. Risankizumab was the first IL-23-specific inhibitor approved for adults with moderately to severely active Crohn's disease in 2022 and later received US approval for ulcerative colitis in June 2024. Mirikizumab, given intravenously in its initial approval, was the first anti-IL-23p19 agent licensed for ulcerative colitis, and it was subsequently approved for Crohn's disease after the VIVID programme. Guselkumab, another p19 antagonist, has been studied in both diseases, with trial programmes extending to combination regimens with golimumab. Because IL-23 is central to a Th17-driven pathway, these agents are also established in psoriasis, which has been an important factor in their development.
JAK inhibitors and S1P receptor modulators
Oral JAK inhibitors block intracellular signalling of multiple cytokines through the JAK–STAT pathway. Tofacitinib was the first to be approved for ulcerative colitis, and upadacitinib later gained approval in both ulcerative colitis and Crohn's disease. Their rapid onset and oral route make them attractive. The ORAL Surveillance trial, a post-marketing noninferiority study in older patients with rheumatoid arthritis and at least one cardiovascular risk factor, compared tofacitinib 5 mg or 10 mg twice daily with an anti-TNF agent. It found higher rates of major adverse cardiovascular events, malignancy, venous thromboembolism and death with tofacitinib. In July 2019 the FDA added a class-wide boxed warning to JAK inhibitors, and comparable warnings followed in other jurisdictions. In the United States, JAK inhibitors for IBD are generally restricted to patients who have failed or do not tolerate anti-TNF therapy, and clinicians are advised to use the lowest effective maintenance dose and to avoid these drugs in patients with high thrombotic or cardiovascular risk. Whether these findings apply to IBD populations, which are usually younger, remains debated.
Sphingosine-1-phosphate (S1P) receptor modulators, including ozanimod and etrasimod, are oral agents that retain lymphocytes in lymph nodes by blocking their egress, which reduces the number of circulating cells reaching the gut. They are approved for moderately to severely active ulcerative colitis but not for Crohn's disease. Their main safety considerations include bradycardia at treatment initiation, infections, and effects on liver enzymes.
Biosimilars, subcutaneous formulations and sequencing
Biosimilars of infliximab and adalimumab are now widely used, and they have reduced the cost of anti-TNF therapy in many health systems, although prescribing practice and reimbursement rules differ by country. Subcutaneous formulations of several agents, including vedolizumab and infliximab, allow home administration and reduce infusion-chair demand, and subcutaneous induction regimens for risankizumab are under regulatory review. Treatment sequencing is individualized. Current practice generally considers disease location, severity, prior exposures, extraintestinal disease and comorbidities such as cardiovascular risk. Loss of response to a biologic is frequently associated with low drug concentrations or anti-drug antibodies, which has led to proactive or reactive therapeutic drug monitoring in some centres.
Head-to-head comparisons remain limited. The VARSITY trial showed that vedolizumab was superior to adalimumab for clinical remission in ulcerative colitis, which supported its positioning as a first-line option in some settings. Few comparable trials exist in Crohn's disease, and most approvals still rest on placebo-controlled studies, so comparative efficacy across classes is still incompletely established.
Surgical treatment
Ulcerative colitis
Because ulcerative colitis is confined to the colon and rectum, removing the colon can eliminate the disease in a way that medication cannot. Surgery is generally reserved for medically refractory disease, dysplasia or colorectal cancer, and life-threatening complications. Surgical indications in UC include medically refractory disease, dysplasia or malignancy, and life-threatening complications, with restorative proctocolectomy and ileal pouch-anal anastomosis (IPAA) representing the standard elective procedure. Estimates of how many patients eventually need an operation vary between sources. One review puts the lifetime figure at approximately 20%-30% of patients with UC, while another cites about 10–15% of all patients with ulcerative colitis requiring a procedure, a figure that reflects the era of widespread biologic use.
The standard operation is total proctocolectomy with IPAA, which removes the colon and rectum and reconstructs intestinal continuity with a pouch joined to the anal canal. The procedure can be completed in two stages, with a temporary diverting ileostomy that is later reversed, or in three stages, beginning with subtotal colectomy. The standard surgical procedure is proctocolectomy with ileal pouch-anal anastomosis (IPAA), which can be performed as a two-stage procedure (proctocolectomy with IPAA and diverting ileostomy followed by ileostomy closure) or as a three-stage procedure. In a 2024 German comparison, the two approaches produced similar results, with pouch failure and failure of improved quality of life during long-term follow-up occurring in 10% of patients without significant differences between them.
Technique and outcomes have changed over time. In a Leuven series of 492 patients operated between 1990 and 2022, the share of laparoscopic procedures rose from 23.2% in the earliest period to 86.0% in the latest, and anastomotic leakage rate decreased from 16.7% (interval A) to 8.4% (interval C). The same study identified delayed construction of the pouch as the most relevant factor in limiting leakage, while cumulative pouch failure stayed at about 8% across the three periods. Functional results remain variable: one long-term cohort reported pouch preservation of 96.5% and 93.1% at 10 and 20 years, yet pouch function was classed as deficient in 26 (47.3%) patients. Daily stool frequency is a common concern, with a median of 8 times per day in one cohort. Older patients were once generally offered a permanent ileostomy because pouch surgery was thought too risky, but several papers have documented similar outcomes with IPAA in terms of safety when compared to younger patients.
Crohn's disease
Surgery in Crohn's disease differs in purpose. It is not a cure, and it is usually aimed at symptoms, complications and preserving intestinal function. For CD, surgery is not a definitive cure. Therefore, intestinal resection is indicated for patients who are refractory to the therapy or who are intolerant to medical treatments. Operations are also performed for obstruction, recurrent sub-obstructions, abdominal abscesses, perforation, massive bleeding or even cancer. The most frequent procedure is ileo-cecal resection and primary reconstruction, which is indicated in patients with CD of distal ileum and/or ileo-colon. Because the disease can recur in many segments over a lifetime, the principle of preserving length is central: the goal of preservation of intestinal length and function is only for Crohn's disease due to potential for multiple resections resulting in loss of bowel. Bowel-sparing techniques such as limited resection and strictureplasty are favoured for fibrostenotic disease.
Recurrence at the anastomosis or elsewhere is the main limitation. In one cohort, the cumulative incidence of surgical recurrence was 16.2% at 5 years and 23.3% at 10 years after surgery, while reported reoperation rates across studies range from 16% to 65% 10 years after a previous surgery. Endoscopic recurrence is far more common and appears earlier, with rates as high as 50-75% at 3 months after surgery, and 50-90% at 12 months. Risk factors include smoking, penetrating or perianal disease, prior surgeries, and extensive small bowel involvement, and urgent surgery was positively associated with surgical disease recurrence in a pediatric and adult cohort.
Indications, stomas and quality of life
Surgery is often a salvage option in acute, severe colitis in either disease. In both UC and CD, surgery can be a salvage procedure for acute, severe disease. Prophylactic colectomy is also considered for colitis-associated dysplasia, and patients with IBD involving at least one-third of the colon carry an increased risk of colorectal cancer, which strengthens this indication. Minimally invasive and robotic approaches have shown favorable short-term outcomes without compromising long-term results.
A permanent stoma remains an accepted choice in selected patients. A permanent stoma is a good option in selected patients, especially the elderly. Temporary diverting ileostomies are used in staged pouch surgery, and their complications include high ileostomy output, dehydration, metabolic disturbances, parastomal hernia, retraction or prolapse of stoma. Surgery generally improves the physical burden of disease, but it has psychological costs. A systematic review of 58 studies found that surgery significantly improved physical quality of life in 90% of patients, but psychological and social challenges persisted, with 38% reporting body image issues and 34% experiencing social isolation. The same review noted that psychological support improved emotional quality of life by 20–30%, and that IPAA patients showing higher satisfaction (70% at 5 years) than Crohn's Disease patients with resections. Surgical planning therefore usually involves a joint decision between gastroenterologists and surgeons, with attention to the quality of life trade-offs and to psychological support before and after the operation.
Complications and long-term risks
Intestinal complications
Most structural complications arise from transmural inflammation and the scarring that follows it, and they are more characteristic of Crohn's disease than of ulcerative colitis. Repeated cycles of mucosal injury can leave fibrotic tissue that narrows the lumen. A stricture is an area of the gastrointestinal tract narrowed by scar tissue caused by repeated bouts of inflammation. Stricturing disease is a leading indication for surgery in Crohn's disease. Obstruction typically produces colicky pain, distention, obstipation, and vomiting. Management is usually multidisciplinary and combines medication, endoscopic and surgical options. Despite recent advances in medical therapy, the progression to stricturing complications has not been significantly altered, and only a subset of patients improve temporarily on medication. Anti-fibrotic agents are under evaluation for this problem.
Transmural disease also favours fistulas and abscesses. About 1 in 3 people with Crohn's disease will develop a fistula. Fistulas may connect loops of bowel, the bladder, or the skin. Imaging is used to exclude a concurrent abscess, which is drained when present. Broad-spectrum antibiotics are started when sepsis is suspected, and in cases of persistent sepsis, the diseased bowel is generally excised, whether an abscess is present or not. Perforation is a further hazard: the bowel wall can tear, letting bacteria leak into the abdomen, which causes peritonitis and can progress to sepsis.
Toxic megacolon is the most feared acute colonic complication. It is potentially fatal and is associated with high morbidity and mortality. Its typical features include fever, a swollen and tender abdomen, frequent bloody diarrhoea, a fast heartbeat, and low blood pressure. Antimotility drugs are avoided during active colitis because of the risk of precipitating it. Treatment combines intravenous corticosteroids with decompression of the colon through a nasogastric tube. Surgery is indicated for toxic megacolon, massive haemorrhage, perforation, peritonitis, or non-response to medical therapy. In one reported case, failure of medical therapy led to emergency total colectomy.
Colorectal cancer risk and surveillance
Long-standing colonic inflammation raises the risk of colorectal cancer, and the risk depends on how much of the colon is involved. Patients with long-standing IBD involving at least a third of the colon are at increased risk. Individuals with extensive colonic involvement face up to a two- to three-fold greater risk, with cumulative risks of about 2% after 10 years, 8% after 20 years, and up to 18% after 30 years of disease duration. The cancer arises through a pathway that differs from sporadic cancer, in which the burden of inflammation is central. Risk appears to be higher in patients with a high prior inflammatory burden, concomitant primary sclerosing cholangitis, or a history of dysplasia. Advances in endoscopic technique and medical care have been accompanied by a falling incidence of colitis-associated cancer over the last 50 years.
Surveillance aims to find dysplasia while it can still be removed endoscopically. Initial colonoscopy screening is recommended 8–10 years after diagnosis in all people with colonic IBD, and immediately on diagnosis of primary sclerosing cholangitis. Later intervals are set by risk: every 1–5 years, depending on the burden of colonic inflammation, family history, primary sclerosing cholangitis, prior dysplasia, and the quality of earlier examinations. Recent practice favours chromoendoscopy with targeted biopsies of visible lesions rather than traditional random biopsies, although there is ongoing debate and conflicting data about the optimal technique. Dysplasia that is clearly delineated is generally resected endoscopically, and referral to a specialized endoscopist or IBD centre is suggested when resectability is uncertain. Because chronic inflammation can lead to a false-positive pathological diagnosis of dysplasia, surveillance continues even when disease is well controlled. Evidence for benefit is observational, since there are no randomized controlled trials comparing surveillance with no surveillance, but population studies report a lower risk of cancer-related death among those under surveillance.
Nutritional and systemic consequences
Micronutrient deficiency is common. The most common deficiencies are iron, vitamin D, vitamin B12, and zinc. Causes include malabsorption, reduced intake, and ongoing losses, and some of these deficiencies are more prominent at diagnosis, while others persist or worsen during treatment.
Anaemia is one of the most frequent systemic complications. In children, approximately one-third of newly diagnosed patients present with anaemia. The mechanisms include iron deficiency from gastrointestinal blood loss and impaired absorption, anaemia of chronic disease driven by hepcidin, deficiency of vitamin B12 or folate, and marrow suppression from some immunomodulators. In anaemia of chronic disease, inflammation raises hepcidin, which reduces iron release from stores and absorption, and the response to oral iron is poor.
Low bone density is also frequent. Up to 50% of patients with IBD have low bone mass or osteoporosis and up to a 60% increased risk of fracture. Corticosteroid exposure, chronic inflammation, reduced physical activity, sarcopenia and vitamin deficiencies all contribute.
Venous thromboembolism is multifactorial, and acquired factors appear to dominate. Active inflammation is the principal modifiable risk, so effective anti-inflammatory treatment is itself preventive. Other factors include smoking, oral contraceptive use, dehydration, immobilization, infection, and hyperhomocysteinaemia, which low folate and vitamin B6 or B12 can cause. Hydration, correction of vitamin deficiencies, mechanical compression, and early mobilization after surgery should always be considered, especially in hospitalised patients.
Special populations and quality of life
Pediatric-onset disease
A substantial minority of people with IBD first present in childhood, and the timing often coincides with puberty. Around one in four patients is diagnosed before adulthood, most of them near the pubertal growth spurt. Growth failure is characterized by delayed skeletal maturation and a late onset of puberty, and it is usually quantified with height-for-age Z-scores or with growth velocity over three to four months. It is common at presentation in Crohn's disease, but less common in ulcerative colitis. Its causes are multiple. Chronic undernutrition and pro-inflammatory cytokines are the two main contributors, and they act partly by disrupting the growth hormone–IGF-1 axis, the pulsatile secretion of gonadotropin-releasing hormone and the growth plate itself. Chronic corticosteroid therapy adds to the disease-related causes of growth impairment. Small bowel involvement has been linked to shorter adult height, and a delay in diagnosis is itself a risk factor for lower final height.
Puberty is affected in parallel. In one cohort of 109 children, about 10% showed delayed puberty, and these patients had significantly lower body mass index. Delayed puberty is more common in patients who have not achieved remission or who have active disease. Pubertal delay is more frequent in boys. Where it causes significant psychological distress, parenteral testosterone may be used under expert endocrine supervision. Bone health is a further concern: in the same cohort, vitamin D deficiency was documented in 81.7% of patients. Management therefore centres on controlling inflammation and promoting mucosal healing, combined with regular measurement of weight, height and pubertal stage. Surgical resection of localized Crohn's disease in otherwise treatment-resistant children has been followed by catch-up growth within about six months, a finding that is relevant to decisions about steroid use and surgery alike.
Pregnancy, fertility and perinatal outcomes
Most women with IBD have fertility rates comparable with the general population, although voluntary childlessness is common among women with IBD. Disease activity is the principal determinant of outcome. Active IBD during pregnancy is associated with adverse outcomes, including spontaneous abortion, small-for-gestational-age infants and preterm birth, which is why remission before conception is emphasized. In a UK tertiary cohort of 130 pregnancies, active disease during pregnancy occurred in about 22% of women who were in remission at conception, compared with nearly 80% of those who were not, and active disease at conception was associated with preterm birth. Prospective data show that flares are common even among women who are quiescent at conception: 37.6% of the 298 women with quiescent disease at conception experienced a flare during pregnancy. Relapse risk appears to differ by subtype, with pregnant women with Crohn's disease having a course similar to non-pregnant women, while those with ulcerative colitis were at higher relapse risk during pregnancy and post-partum.
Evidence on outcomes in offspring is mixed. Some studies could not show differences between pregnant patients with or without IBD, while a recent meta-analysis suggests a significantly higher risk for preterm birth, small for gestational age, and stillbirth in patients with IBD. Older population-based data reported that premature delivery was almost twice as likely in women with IBD, and cesarean delivery about 1.5 times as likely, though these analyses did not adjust for medication use or disease activity. Pregnancy-specific medication decisions remain a central concern: with few exceptions, most medications used in the treatment of IBD are considered safe during pregnancy and breastfeeding. Fear of medication-related risk to the fetus is nonetheless the most frequent reason for non-adherence, which makes preconception counselling and a planned, rather than mistimed, conception important.
Psychological burden and quality of life
Psychiatric comorbidity is well documented. IBD, which includes Crohn's disease and ulcerative colitis, is associated with higher rates of anxiety and depression compared to the general population. A systematic review of 79 studies estimated that about 15% of patients with IBD have depression and over 20% of patients have symptoms of depression. Anxiety symptoms were reported in up to a third of patients, and the proportion was higher among those with active disease. Reported figures vary widely between settings: a multicentre study in Ethiopia found anxiety and depression symptoms in 5.1% and 7.1% of patients, respectively, whereas a smaller study in another setting found symptoms suggestive of anxiety in 62.6% and depression in 19%. These differences probably reflect study populations and screening instruments as much as true variation.
The relationship between psychological symptoms and inflammatory activity is inconsistent. One study found no significant associations between psychiatric symptoms and calprotectin levels, while others have reported greater risk in active disease. The proposed mechanisms include bidirectional communication via the gut–brain axis and chronicity of symptoms, and impaired quality of life and reduced social functioning. Quality of life is consistently affected. In one Australian cohort, patients with anxiety had markedly lower IBD-specific quality-of-life scores than those without it (44.0 versus 57.4). Depressive, anxiety, and stress symptoms were negatively associated with quality of life in multivariable analysis. Psychiatric disorders can also reduce medication adherence and heighten the occurrence of active disease, which links mental health directly to disease control. Despite this, most of these patients are not getting the mental health treatment they need, and routine screening is widely advocated.
Gut–brain axis research, quality of life measurement, and mental health services for people with chronic disease therefore form a common frame for understanding how IBD affects work, relationships and social participation over the long term.
History of research and classification
Early descriptions of ulcerative colitis
Reports of chronic, bloody diarrhoea without an identifiable infectious cause accumulated through the nineteenth century, but the disease lacked a settled identity. Giovanni Battista Morgagni's 1769 observations are among the earliest accounts that later writers have reinterpreted as Crohn's-type disease. For ulcerative colitis, Samuel Wilks's 1859 case report, concerning a patient named Miss Bankes, is generally treated as the first description of the condition. Ulcerative colitis was first described in 1875 by two English physicians, Wilks and Moxon, who distinguished it from diarrheal diseases caused by infectious agents. In 1888, William Hale White's case studies of diarrhoea without a demonstrable cause helped establish the term in general medical usage. Thomas Dalziel's 1913 paper, which described a chronic interstitial enteritis, is cited as an early account of the small-bowel form.
The 1932 description and the naming of Crohn's disease
Small-bowel inflammation was, at the time, widely read as intestinal tuberculosis. In May 1932, Burrill Crohn, Leon Ginzburg and Gordon Oppenheimer presented a series of 14 patients with inflammation of the terminal ileum. The surgical work was performed by Albert Berg, whose name was initially omitted from the publication. The lesion was first labelled "regional ileitis," but it was quickly renamed after Crohn. The ileal focus of the 1932 report was not a complete picture: it was not until 1965, however, that Crohn's colitis was recognized in the United States. The British had documented colonic involvement in 1959, and US physicians took several more years to accept that the disease could extend past the ileocaecal valve.
Criteria, classification and the Montreal system
Early diagnosis depended largely on barium radiography, as the 1932 series showed, and on surgical specimens. Endoscopic, histological and radiological criteria were refined over the following decades, and the classification of phenotype was gradually standardised. The Montreal classification, reached through a consensus process, was further refined in 2005 to be what the Montreal classification is today. Its Crohn's axes cover age at diagnosis, location and behaviour, and a later revision added an age band for children under 16. A pediatric modification, the Paris classification, classifies age at diagnosis as A1a (0 to <10 years), A1b (10 to <17 years), A2 (17 to 40 years), and A3 (>40 years), reflecting the fact that the adult scheme fails to capture change over time in children. Guidelines from national and international societies have since been built on these shared descriptors, which make trial populations and cohorts comparable.
From steroids and surgery to targeted biologics
Until the 1950s and 1960s, treatment rested largely on corticosteroids, surgical resection and supportive measures. Immunosuppressants and aminosalicylates entered practice later, and the decisive shift came with biologic therapy. The first milestone was infliximab, a monoclonal antibody against tumour necrosis factor. On May 28, 1998, the Food and Drug Administration (FDA) Gastrointestinal Advisory Committee voted to approve infliximab for Crohn's disease, and the FDA approval followed in August of that year. The initial indications were deliberately narrow: single dose therapy for the treatment of patients with moderate-severe inflammatory disease refractory to conventional therapy, and a regimen for draining external fistulae. Later randomised trials supported use in fistulising disease, with a fistula response after 14 weeks in the ACCENT 2 trial. Infliximab's extension to ulcerative colitis came in 2005, and its success established targeted therapy as a viable approach in immune-mediated disease. Subsequent agents, including other anti-TNF drugs, anti-integrins and anti-interleukin-12/23 therapies, were added in the following years. Biosimilars followed as well, and the first biosimilar for IBD approved in the United States was CT-P13, approved in April 2016.
Emerging therapies and the search for a cure
Stem cell transplantation
Autologous hematopoietic stem cell transplantation (HSCT) is the most clinically developed cell-based approach. It is used mainly for severe, treatment-refractory Crohn's disease. Its rationale comes from work on autoimmune diseases in general: mechanistic studies propose that transplantation can reset chronic autoimmunity by clearing immune memory and rebuilding the immune system, which restores immune tolerance via eradication of immune memory and reconfiguration of the immune system.
The main randomized evidence comes from the ASTIC trial, which compared transplantation with conventional care in patients who had failed several immunosuppressive or biologic agents. Among 23 patients who underwent HSCT and 22 controls, sustained disease remission was achieved in 2 patients undergoing HSCT (8.7%) vs 1 control patient (4.5%), a difference that was not statistically significant. A secondary finding was that 14 patients undergoing HSCT (61%) vs 5 control patients (23%) had discontinued immunosuppressive or biologic agents or corticosteroids for at least 3 months. Safety remains the central concern. A meta-analysis emphasized that the balance between risk and benefit is delicate because transplantation carries mortality and adverse events, and early series reported transplant-related deaths. Less intensive protocols have been explored in response. In a single-centre series, fourteen patients were submitted to non-myeloablative autologous hematopoietic stem cell transplantation using lower doses of cyclophosphamide, and in the wider European series 53/78 (68%) experienced complete remission or significant improvement in symptoms at a median follow-up of 41 months. These are uncontrolled data and are not directly comparable with the randomized trial.
B-cell-targeted and CAR-T approaches
Chimeric antigen receptor (CAR) T-cell therapy engineers a patient's T cells to recognize a defined surface antigen. In inflammatory bowel disease, the main interest has been in B cells. Evidence points to mucosal B cells, plasmablasts and disease-associated antibody responses as possible drivers of ulcerative colitis. The first published human experience is a single case: a CD19-directed CAR-T product was given to a patient with severe, therapy-resistant ulcerative colitis, and the report described long-term remission of intestinal inflammation. The safety picture is incomplete. In one reported case, a patient treated with CAR-T cells for lymphoma developed chronic diarrhea resembling IBD, and CAR T cells were substantially enriched in the colon lamina propria, which suggested a drug-associated colitis rather than IBD itself.
Regulatory T-cell (Treg) therapies aim to restore suppression rather than deplete pathogenic cells. Treg numbers and function are reduced relative to effector T cells in IBD, which is the basis for engineering antigen-specific Tregs. Candidate designs include interleukin-23 receptor-targeted CAR Tregs, aimed at T helper 17-driven inflammation, and flagellin-specific CAR Tregs preferentially home to damaged intestinal tissues in laboratory work. A recent systematic review found that available human evidence remains limited, with sparse clinical experience and short follow-up. Conventional regulatory T-cell products are also under test. Early trials are evaluating allogeneic IL-10-producing type 1 regulatory T cells and autologous transforming growth factor-β-secreting regulatory T cells.
Barrier restoration, tolerogenic vaccines and antigen-specific interventions
Interventions in this group share one goal: reducing inflammation without broad suppression of the immune system. Strategies to repair the epithelial barrier, including its junctions, mucus layer and epithelial regeneration, are at the preclinical or early stage. Their aim is to limit the entry of luminal antigens into the mucosa. Tolerogenic vaccines would instead present specific gut-derived antigens so that the immune system learns to tolerate them. Such approaches have been studied in animal models of colitis, but clinical data in IBD are scarce. Antigen-specific strategies share this uncertainty: their efficacy depends on identifying the right antigens, and it is not yet clear whether tolerance induced in one setting persists once the treatment ends.
Microbiome-based interventions
Fecal microbiota transplantation (FMT) is the most studied microbiome-based option. Its use in recurrent infectious colitis is established. In ulcerative colitis, a 2019 randomized trial in 73 adults with mild to moderate disease found that the proportion achieving steroid-free remission at 8 weeks was 32% with donor FMT vs 9% with autologous FMT. A later meta-analysis of double-blind trials, comprising six trials and 324 patients, concluded that compared with placebo, FMT has significant benefit in inducing combined clinical and endoscopic remission, although the benefit was observed over the short term. Proposed mechanisms include altering microbiota dysbiosis, reducing the intestinal permeability, and increasing the production of short-chain fatty acids. Questions remain about standardized donor selection and preparation, the durability of remission, and long-term safety, all of which need larger and longer trials.
Engineered microbial consortia are defined mixtures of bacterial strains selected or modified to produce beneficial metabolites, to compete with pathogenic organisms, or to replace missing functions. This approach aims to address the reproducibility problems of donor-derived material. Bacteriophage therapy uses viruses that infect specific bacteria, with the aim of removing particular pathogenic strains while sparing the rest of the community. Both are at an early stage in IBD. Evidence still needed includes controlled human trials, data on how engineered strains persist and interact with the resident microbiota, and assessment of the risk of transferring resistance genes or unwanted microorganisms.
Unresolved questions, access and health systems
Open scientific questions
The event that starts IBD is still unidentified. Risk genes and environmental exposures explain only part of the picture, and no single trigger has been confirmed. The relationship between microbes and inflammation is similarly unsettled. Dysbiosis is reproducibly seen in patients, but it is unclear whether altered communities drive mucosal inflammation or are reshaped by it through inflammation, medication, and diet. Interventions that manipulate the microbiota have produced mixed results, which keeps the causal question open.
Why some patients fail several advanced therapies also remains unexplained. Proposed explanations include low serum drug concentrations, anti-drug antibodies, dominance of an inflammatory pathway that a given agent does not block, persistent epithelial injury, and fibrostenotic disease in which fibrosis rather than active inflammation drives symptoms. Reliable biomarkers that predict which explanation applies to a given patient are not yet in routine use.
Cost, biosimilars and access
Biologic drugs cost far more than conventional therapies, and one review of European data cited annual biologic costs of about €1,782 per patient with Crohn's disease and €286 per patient with ulcerative colitis. Biologic prices are significantly higher than those of traditional medications, creating a substantial burden on healthcare systems and limiting access to treatment in resource-constrained settings. Available data indicate that biologics cost €1782 per year for patients with CD and €286 for UC patients in Europe.
Biosimilars are the main tool for narrowing this gap. Their price advantage can be large: for one ustekinumab product, the originator list price was roughly five to twelve times that of the biosimilar alternatives on the market. Competitive bidding in Norway was reported to secure a 40% cost saving on infliximab. In a 2024 international survey of 233 physicians, about half of respondents said the cost of biologics limited patients' access to therapy, and the lower price of biosimilars compared with reference products was the main driver of choice in IBD. Savings do not automatically reach patients. An Italian population study found that the share of patients on advanced therapy rose while total spending on those therapies fell by about a fifth, a change the authors attributed mainly to TNF-inhibitor biosimilars.
Access is also uneven geographically and socially. Across Europe, many countries restrict access despite professional society guideline recommendations. In the United States, rural patients were more likely to be receiving no therapy for IBD and less likely to receive advanced therapies, and a Canadian population cohort found that rural residents had fewer gastroenterology visits and were less likely to have a gastroenterologist as their primary IBD care provider. Patients in low- and middle-income countries and in rural regions often face shortages of gastroenterologists, limited diagnostic capacity, and poor access to advanced therapies. A scoping review of adult studies found that most work on inequality concerned race and ethnicity, with socioeconomic status and rurality following, and that qualitative work on these experiences is scarce.
Treatment strategy: early intensity and monitoring
The central debate concerns how aggressively to treat at diagnosis. The top-down approach uses immunomodulators and biologics early, whereas step-up begins with corticosteroids and escalates only in patients who are refractory or dependent on steroids. Top-down therapy has been associated with higher rates of mucosal healing, but whether this translates into fewer surgeries and hospitalizations has been contested. The PROFILE trial, which randomized 386 adults with newly diagnosed, active Crohn's disease to early infliximab plus an immunomodulator or to step-up care, reported better one-year outcomes for top-down treatment, and its investigators proposed that top-down therapy should be considered standard for newly diagnosed active disease. Lower risks of abdominal surgery and of complications or hospitalization persisted over five years, although most step-up patients eventually required maintenance immunomodulator or biologic therapy. The same trial's biomarker did not show clinical utility. Earlier trials of early thiopurine use had not shown consistent advantages, and one review noted that whether such paradigms outperform conventional step-care for disease progression and bowel damage remains a matter of active debate.
Proactive therapeutic drug monitoring, in which drug and antibody levels guide dose changes, is debated for similar reasons. Trials comparing it with reactive, symptom-driven adjustment have yielded mixed results, and assay availability and cost limit its use in many centres.
The balance between efficacy and long-term safety underlies all of these choices. Intensive combination therapy adds exposure to immunosuppression, and the PROFILE investigators reported fewer adverse events and serious adverse events in the top-down group, with no difference in serious infections. Long-term data on malignancy and other rare risks of newer agents are still accumulating, so the appropriate threshold for escalation remains a matter of clinical judgement.
References
- Inflammatory Bowel Disease (IBD)labs.icahn.mssm.edu
- An Esophagogastroduodenal Crohn's-Like Disease in a Long-Standing Pan-Ulcerative Colitis Patientncbi.nlm.nih.gov
- Reclassification of Inflammatory Bowel Disease Type Unclassified by Small Bowel Capsule Endoscopyncbi.nlm.nih.gov
- IBS vs IBDcrohnscolitisfoundation.org
- Inflammatory bowel disease and irritable bowel syndrome IBD-first chek diagnostic panelimage-ppubs.uspto.gov
- Irritable Bowel Syndrome in Inflammatory Bowel Disease: An Evidence-Based Practical Reviewncbi.nlm.nih.gov
- Clinical features of inflammatory bowel disease unclassified: a case-control studyncbi.nlm.nih.gov
- An Overview of Inflammatory Bowel Disease Unclassified in Children - PMCpmc.ncbi.nlm.nih.gov
- Pathology Outlines - Inflammatory bowel disease, indeterminate typepathologyoutlines.com
- Irritable Bowel Syndrome/Inflammatory Bowel Disease Overlap: Less Common Than We Thinkncbi.nlm.nih.gov
- Epidemiology and Natural History of IBD in the Paediatric Agencbi.nlm.nih.gov
- Myositis as an Extraintestinal Manifestation of Ulcerative Colitis: A Case Report and Literature Reviewncbi.nlm.nih.gov
- Extraintestinal manifestations in Crohn’s disease and ulcerative colitis: results from a prospective, population-based European inception cohort: Scandinavian Journal of Gastroenterology: Vol 50 , No 3 - Get Accesstandfonline.com
- Beyond the gut: Extraintestinal manifestations of ulcerative colitis - Mayo Clinicmayoclinic.org
- Extraintestinal manifestations of Crohn's disease - PMC - NIHpmc.ncbi.nlm.nih.gov
- Extraintestinal manifestations of Crohn's disease: prevalence and related factors - PubMedpubmed.ncbi.nlm.nih.gov
- Extra-Intestinal Manifestations of Inflammatory Bowel Diseasencbi.nlm.nih.gov
- A Review of Extraintestinal Manifestations & Medication-Induced Myocarditis and Pericarditis in Pediatric Inflammatory Bowel Diseasencbi.nlm.nih.gov
- Extraintestinal Manifestations in Inflammatory Bowel Disease: From Pathophysiology to Treatmentncbi.nlm.nih.gov
- Extraintestinal manifestations of inflammatory bowel disease - PubMedpubmed.ncbi.nlm.nih.gov
- Pathogenesis and clinical perspectives of extraintestinal manifestations in inflammatory bowel diseasesirjournal.org
- Extraintestinal manifestations in inflammatory bowel diseasewjgnet.com
- How to predict clinical relapse in inflammatory bowel disease patientswjgnet.com
- Stress as a Trigger for Relapses in IBD: A Case-Crossover Studyncbi.nlm.nih.gov
- Modifiable Factors Influencing Disease Flares in Inflammatory Bowel Disease: A Literature Overview of Lifestyle, Psychological, and Environmental Risk Factorsdoi.org
- Factors influencing the relapse of patients with inflammatory bowel disease - PubMedpubmed.ncbi.nlm.nih.gov
- Serum biomarkers confirming stable remission in inflammatory bowel diseasencbi.nlm.nih.gov
- Crohn Disease Pathology: Overview, Epidemiology, Etiologyemedicine.medscape.com
- Methods of diagnosing inflammatory bowel diseaseimage-ppubs.uspto.gov
- Endoscopic Skipping, Stricturing, and Penetrating Complications in Crohn’s Disease on Tandem Ileo-colonoscopy and Cross-sectional Imaging: A Retrospective Cohort Studyacademic.oup.com
- A close view on histopathological changes in inflammatory bowel disease, a narrative review - Kellermann - Digestive Medicine Researchdmr.amegroups.org
- Methods for treating inflammatory bowel disease using prostate specific membrane antigen (PSMA) inhibitorsimage-ppubs.uspto.gov
- Crohn's disease - Libre Pathologylibrepathology.org
- Surgical Planning in Penetrating Abdominal Crohn's Diseasencbi.nlm.nih.gov
- Patients With Stricturing or Penetrating Crohn’s Disease Phenotypes Report High Disease Burden and Treatment Needsncbi.nlm.nih.gov
- Evolution of Clinical Behavior in Crohn's Disease: Factors Associated with Complicated Disease and Surgery - PubMedpubmed.ncbi.nlm.nih.gov
- Bidirectional Montreal Classification Better Captures Crohn’s Disease Complicationshcplive.com
- Tight Control Management in Perianal Crohn's Diseaseclinicaltrials.gov
- The Bottom Line: A Multidisciplinary Approach Is Key to Treating Perianal Fistulizing Crohn’s Diseasencbi.nlm.nih.gov
- Multidisciplinary Team (MDT) Approach to Diagnosis & Management of Perianal Crohn's Diseasecrohnscolitisfoundation.org
- A rolling phenotype in Crohn's diseasencbi.nlm.nih.gov
- European consensus on the histopathology of inflammatory bowel disease - ScienceDirectsciencedirect.com
- Ulcerative colitis (UC)-associated colorectal neoplasia markersimage-ppubs.uspto.gov
- European consensus on the histopathology of inflammatory bowel disease☆academic.oup.com
- Pathology Outlines - Ulcerative colitis and proctitispathologyoutlines.com
- Histomorphological Diagnosis of Ulcerative Colitis and Associated Conditionsintechopen.com
- pmc.ncbi.nlm.nih.govpmc.ncbi.nlm.nih.gov
- Frontiersfrontiersin.org
- Ulcerative colitis - ScienceDirectsciencedirect.com
- Ulcerative colitis (UC)-associated colorectal neoplasia markersimage-ppubs.uspto.gov
- Methods for improving inflammatory bowel disease diagnosisimage-ppubs.uspto.gov
- Gut dysbiosis and clinical phases of pancolitis in patients with ulcerative colitis - PMCpmc.ncbi.nlm.nih.gov
- What Is Pancolitis? 8 Facts To Know for Ulcerative Colitismycrohnsandcolitisteam.com
- Histological evaluation in ulcerative colitisacademic.oup.com
- Histological evaluation in ulcerative colitis - PubMedpubmed.ncbi.nlm.nih.gov
- Surveillance of patients with chronic ulcerative colitis. WHO Collaborating Centre for the Prevention of Colorectal Cancer - PMCpmc.ncbi.nlm.nih.gov
- Inter‐Rater Disagreements in Applying the Montreal Classification for Crohn's Disease: The Five‐Nations Survey Study - Ukashi - 2025 - United European Gastroenterology Journal - Wiley Online Libraryonlinelibrary.wiley.com
- Montreal Classification — Crohn's (A/L/B) & UC (E/S)gastroagi.com
- Crohn's Montreal Classification: A, L, B, and p Explainedaidyhq.com
- Pediatric modification of the Montreal classification for inflammatory bowel disease: the Paris classification - PubMedpubmed.ncbi.nlm.nih.gov
- A Study of Guselkumab in Participants With Moderately to Severely Active Ulcerative Colitiscdn.clinicaltrials.gov
- Ulcerative Colitis: Clinical Trial Endpoints Guidance for Industryfda.gov
- Infliximab Biosimilar "Pfizer" Drug Use Investigation (Crohn's Disease or Ulcerative Colitis)cdn.clinicaltrials.gov
- A Study of Vedolizumab in People With Ulcerative Colitis and Crohn's Diseasecdn.clinicaltrials.gov
- Frontiersfrontiersin.org
- The ulcerative colitis endoscopic index of severity score is superior to reflecting long-term prognosis in ulcerative colitis patients treated with vedolizumabncbi.nlm.nih.gov
- Post-Marketing Use Of CT-P13 (Infliximab) For Standard Of Care Treatment Of Inflammatory Bowel Diseasecdn.clinicaltrials.gov
- Post-Marketing Use Of CT-P13 (Infliximab) For Standard Of Care Treatment Of Inflammatory Bowel Diseasecdn.clinicaltrials.gov
- Long-Term Safety Of PF-00547659 In Ulcerative Colitiscdn.clinicaltrials.gov
- The burden of inflammatory bowel disease in Europe - ScienceDirectsciencedirect.com
- The epidemiology of inflammatory bowel disease: balance between East and West? A narrative review - Hammer - Digestive Medicine Researchdmr.amegroups.org
- Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies - ScienceDirectsciencedirect.com
- pmc.ncbi.nlm.nih.govpmc.ncbi.nlm.nih.gov
- Sex-Based Differences in Incidence of Inflammatory Bowel Diseases—Pooled Analysis of Population-Based Studies From Western Countries - ScienceDirectsciencedirect.com
- Gender Differences in Inflammatory Bowel Diseasekarger.com
- Epidemiology of inflammatory bowel disease: Is there a shift towards onset at a younger age? - PubMedpubmed.ncbi.nlm.nih.gov
- Global Epidemiology and Burden of Elderly-Onset Inflammatory Bowel Disease: A Decade in Reviewncbi.nlm.nih.gov
- Sex-Based Differences in Incidence of Inflammatory Bowel Diseases-Pooled Analysis of Population-Based Studies From Western Countries - PubMedpubmed.ncbi.nlm.nih.gov
- Sex-based differences in the incidence of inflammatory bowel diseases-pooled analysis of population-based studies from the Asia-Pacific region - PubMedpubmed.ncbi.nlm.nih.gov
- Understanding and Preventing the Global Increase of Inflammatory Bowel Disease - Gastroenterologygastrojournal.org
- Global evolution of inflammatory bowel disease across epidemiologic stagesnature.com
- Epidemiology, pathogenesis, diagnosis, and treatment of inflammatory bowel disease: Insights from the past two yearsovid.com
- The four epidemiological stages in the global evolution of inflammatory bowel diseasenature.com
- The Rise of Crohn’s Disease and Ulcerative Colitis Around the Worldhealthcentral.com
- Understanding and Preventing the Global Increase of Inflammatory Bowel Disease - ScienceDirectsciencedirect.com
- Clinical epidemiology of inflammatory bowel disease: incidence, prevalence, and environmental influences - Gastroenterologygastrojournal.org
- IBD barriers across the continentsjournals.sagepub.com
- Male predominance in inflammatory bowel disease despite similar disease activity: A large retrospective cohort study - PMCpmc.ncbi.nlm.nih.gov
- Epidemiology of Inflammatory Bowel Disease across the Ages in the Era of Advanced Therapiesacademic.oup.com
- pmc.ncbi.nlm.nih.govpmc.ncbi.nlm.nih.gov
- Heritability of Crohn’s disease and ulcerative colitis: a Swedish nationwide population-based twin studyacademic.oup.com
- The Genetics of Inflammatory Bowel Diseaselink.springer.com
- Frontiersfrontiersin.org
- The genetics of inflammatory bowel disease - PubMedpubmed.ncbi.nlm.nih.gov
- The Genetics of Inflammatory Bowel Diseaseiris.unil.ch
- Cell atlas of the healthy and ulcerative colitis human colonimage-ppubs.uspto.gov
- Crohn’s disease: NOD2, autophagy and ER stress converge - PMCpmc.ncbi.nlm.nih.gov
- Genetics and pathogenesis of inflammatory bowel disease - PMCpmc.ncbi.nlm.nih.gov
- Down the line from genome-wide association studies in inflammatory bowel disease: the resulting clinical benefits and the outlook for the future: Expert Review of Clinical Immunology: Vol 11 , No 1 - Get Accesstandfonline.com
- Genetic Overlap Between Inflammatory Bowel Disease and ...medrxiv.org
- Rare and common variant discovery in complex disease: the IBD case studyacademic.oup.com
- Mutation spectrum of NOD2 reveals recessive inheritance as a main driver of Early Onset Crohn’s Diseasenature.com
- Integrative multi-omics analysis identifies genetically supported druggable targets for inflammatory bowel disease - PubMedpubmed.ncbi.nlm.nih.gov
- Frontiersfrontiersin.org
- (PDF) Ulcerative colitis and Crohn's disease in an unselected population of monozygotic and dizygotic twins. A study of heritability and the influence of smokingacademia.edu
- Family and twin studies in inflammatory bowel diseasewjgnet.com
- Familial occurrence and inheritance studies in inflammatory bowel disease - PubMedpubmed.ncbi.nlm.nih.gov
- Genetics of inflammatory bowel disease: beyond NOD2 - ScienceDirectsciencedirect.com
- Environmental risk factors of inflammatory bowel disease: toward a strategy of preventative healthncbi.nlm.nih.gov
- The Role of Environmental and Nutritional Factors in the Development of Inflammatory Bowel Diseases: A Case–Control Studyncbi.nlm.nih.gov
- Review: Influence of Environmental Factors in Inflammatory Bowel Disease - Mass General Advances in Motionadvances.massgeneral.org
- The epidemiology of inflammatory bowel disease: exploring the impacts of environmental factors - PMCpmc.ncbi.nlm.nih.gov
- Environmental risk factors of inflammatory bowel disease: toward a strategy of preventative healthacademic.oup.com
- Gut Microbiota Serves as a Crucial Independent Biomarker in Inflammatory Bowel Disease (IBD)ncbi.nlm.nih.gov
- Gut microbiota in the pathogenesis of inflammatory bowel diseaselink.springer.com
- Is the microbiome the answer to inflammatory bowel disease: systematic review - PubMedpubmed.ncbi.nlm.nih.gov
- Gut Microbiota Serves as a Crucial Independent Biomarker in Inflammatory Bowel Disease (IBD)doi.org
- Diagnosis of Crohn’s disease and ulcerative colitis using the microbiomebmcmicrobiol.biomedcentral.com
- Genetic risk, dysbiosis, and treatment stratification using host genome and gut microbiome in inflammatory bowel disease - PMCpmc.ncbi.nlm.nih.gov
- Role of Infections in the Manifestation or Reactivation of Inflammatory Bowel Diseasesacademic.oup.com
- Aetiology of inflammatory bowel disease (IBD): Role of intestinal microbiota and gut-associated lymphoid tissue immune response - ScienceDirectsciencedirect.com
- Gastrointestinal Infection Increases Odds of Inflammatory Bowel Disease in a Nationwide Case-Control Study - PubMedpubmed.ncbi.nlm.nih.gov
- Associations Between Gastrointestinal Infection and New-Onset IBD - Gastroenterology Advisorgastroenterologyadvisor.com
- Seasonal variation of enteric infections and inflammatory bowel disease - PubMedpubmed.ncbi.nlm.nih.gov
- Enteric Infections Are Common in Patients with Flares of Inflammatory Bowel Disease - PMCpmc.ncbi.nlm.nih.gov
- These Environmental Factors Increase the Risk of IBDtime.com
- Impact of environmental and dietary factors on the course of inflammatory bowel disease - PMCpmc.ncbi.nlm.nih.gov
- Environmental factors affecting inflammatory bowel disease: have we made progress? - PubMedpubmed.ncbi.nlm.nih.gov
- Frontiersfrontiersin.org
- Frontiersfrontiersin.org
- Frontiersfrontiersin.org
- Enteric Viruses and Inflammatory Bowel Diseasencbi.nlm.nih.gov
- Immunopathogenesis of inflammatory bowel disease - PMCpmc.ncbi.nlm.nih.gov
- Pro-Inflammatory Cytokines in the Pathogenesis of IBD - PMCpmc.ncbi.nlm.nih.gov
- Differential Roles for Interleukin-23 and Interleukin-17 in Intestinal Immunoregulation: Immunitycell.com
- Article Differential Roles for Interleukin-23 and Interleukin-cell.com
- The Role of IL-23 in the Pathogenesis and Therapy of Inflammatory Bowel Diseasencbi.nlm.nih.gov
- An Intestinal Th17 Subset is Associated with Inflammation in Crohn’s Disease and Activated by Adherent-invasive Escherichia coli - PMCpmc.ncbi.nlm.nih.gov
- The IL23-IL17 Immune Axis in the Treatment of Ulcerative Colitis: Successes, Defeats, and Ongoing Challengesncbi.nlm.nih.gov
- (PDF) Immunopathogenesis of Ulcerative Colitis and Crohn's Diseaseresearchgate.net
- All are Equal, Some are More Equal: Targeting IL 12 and 23 in IBD &ndadovepress.com
- Interleukin-23 Involved in Fibrotic Autoimmune Diseases: New Discoveriesncbi.nlm.nih.gov
- Antibody derivativesimage-ppubs.uspto.gov
- Interleukin-23 and Th17 Cells in the Control of Gut Inflammationncbi.nlm.nih.gov
- The Current Status of Molecular Biomarkers for Inflammatory Bowel Diseasencbi.nlm.nih.gov
- Endoscopy in Inflammatory Bowel Disease: Indications, Timing, and Biopsy Protocol - ScienceDirectsciencedirect.com
- Inflammatory Bowel Disease Workup: Approach Considerations, Laboratory Studies, Imaging Studiesemedicine.medscape.com
- Diagnostic Procedures for Inflammatory Bowel Disease: Laboratory, Endoscopy, Pathology, Imaging, and Beyond - PMCpmc.ncbi.nlm.nih.gov
- Diagnostic Procedures for Inflammatory Bowel Disease: Laboratory, Endoscopy, Pathology, Imaging, and Beyondncbi.nlm.nih.gov
- Diagnostic Accuracy of Fecal Calprotectin for Predicting Relapse in Inflammatory Bowel Disease: A Meta-Analysisncbi.nlm.nih.gov
- Fecal Calprotectin for the Diagnosis and Management of Inflammatory Bowel Diseasesjournals.lww.com
- Fecal calprotectin and endoscopic scores: The cornerstones in clinical practice for evaluating mucosal healing in inflammatory bowel disease - PMCpmc.ncbi.nlm.nih.gov
- Diagnosis and Monitoring in Inflammatory Bowel Disease: Who, When, Where, and Howlink.springer.com
- Impact of Delayed Diagnosis in IBD on Clinical Outcomes and Healthcare Deliverydoi.org
- A contemporary and critical appraisal of ‘indeterminate colitis’nature.com
- Long-term classification stability and treatment patterns of inflammatory bowel disease unclassified: a longitudinal observational study - PMCpmc.ncbi.nlm.nih.gov
- Indeterminate Colitis/Inflammatory Bowel Disease Unclassified (IBD-U)link.springer.com
- Endoscopic diagnosis and management of adult inflammatory bowel disease: a consensus document from the American Society for Gastrointestinal Endoscopy IBD Endoscopy Consensus Panel - Gastrointestinal Endoscopygiejournal.org
- Diagnostic Accuracy of Fecal Calprotectin for Predicting Relapse in Inflammatory Bowel Disease: A Meta-Analysis - PMCpmc.ncbi.nlm.nih.gov
- Accuracy of three different fecal calprotectin tests in the diagnosis of inflammatory bowel diseaseirjournal.org
- Factors Associated With Loss of Fecal Biomarker Accuracy During Routine Assessment of Inflammatory Bowel Disease - PMCpmc.ncbi.nlm.nih.gov
- Changing treatment paradigms for the management of inflammatory bowel disease - PMCpmc.ncbi.nlm.nih.gov
- Benefits and Challenges of Treat-to-Target in Inflammatory Bowel Diseasemdpi.com
- [Evolving therapeutic targets in inflammatory Bowel Disease: mucosal healing as an emerging end point] - PubMedpubmed.ncbi.nlm.nih.gov
- What Are the Targets of Inflammatory Bowel Disease Management - PubMedpubmed.ncbi.nlm.nih.gov
- Anti-TNF Drugs versus Long-Term Steroid Use for Patients with Inflammatory Bowel Diseases - NCBI Bookshelfncbi.nlm.nih.gov
- Thiopurines and Methotrexate Use in IBD Patients in a Biologic Era - PubMedpubmed.ncbi.nlm.nih.gov
- Thiopurine withdrawal during sustained clinical remission in inflammatory bowel disease: relapse and recapture rates, with predictive factors in 237 patientsncbi.nlm.nih.gov
- Thiopurine monotherapy is effective in ulcerative colitis but significantly less so in Crohn’s disease: long-term outcomes for 11 928 patients in the UK inflammatory bowel disease bioresourcencbi.nlm.nih.gov
- AGA Living Clinical Practice Guideline on the Pharmacologic Management of Moderate-to-Severe Crohn’s Disease - Gastroenterologygastrojournal.org
- Exclusive enteral nutrition for induction of remission in Crohn’s disease in adults: A systematic review and meta-analysis of randomized trials and real-world studieslink.springer.com
- Exclusive enteral nutrition for induction of remission in Crohn's disease in adults: A systematic review and meta-analysis of randomized trials and real-world studies - PubMedpubmed.ncbi.nlm.nih.gov
- Enteral Nutrition in Crohn’s Disease: A Comprehensive Review of Its Role in Induction and Maintenance of Remission and Perioperative Management in Adult Patientsncbi.nlm.nih.gov
- Crohnscolitisfoundationcrohnscolitisfoundation.org
- Full article: Selective biologics for ulcerative colitis and Crohn’s diseasetandfonline.com
- Benefit-Risk Assessment of Vedolizumab in the Treatment of Crohn's Disease and Ulcerative Colitis - PubMedpubmed.ncbi.nlm.nih.gov
- Efficacy of Vedolizumab in Crohn's Disease Patients Naive to Biological Therapyclinicaltrials.gov
- Real-world clinical effectiveness and safety of vedolizumab and anti-tumor necrosis factor alpha treatment in ulcerative colitis and Crohn’s disease patients: a German retrospective chart reviewncbi.nlm.nih.gov
- Vedolizumab for the treatment of fistulizing Crohn's diseaseimage-ppubs.uspto.gov
- Safety of Janus Kinase Inhibitors in Inflammatory Bowel Diseaseslink.springer.com
- How To Safely Use JAK Inhibitors in Patients with Inflammatory Bowel Diseaselink.springer.com
- Important safety information for Janus kinase (JAK) inhibitorstga.gov.au
- Prevalence of ORAL Surveillance-like Cardiovascular Risk Factors in Adults Patients With Inflammatory Bowel Diseases: National Estimates From the United Statesncbi.nlm.nih.gov
- Mirikizumab as Induction and Maintenance Therapy for Ulcerative Colitisnejm.org
- Risankizumab for Ulcerative Colitis Two Randomized Clinical Trialsbinasss.sa.cr
- An evaluation of risankizumab for the treatment of moderate-to-severe ulcerative colitis - PubMedpubmed.ncbi.nlm.nih.gov
- The Role of IL-23 Inhibitors in Crohn’s Diseasencbi.nlm.nih.gov
- Role of Mirikizumab in the Treatment of Inflammatory Bowel Disease—From Bench to Bedsidencbi.nlm.nih.gov
- A Breakthrough UC Drug Is Approved Following a Rigorous Mount Sinai-Led Trialreports.mountsinai.org
- AbbVie Submits Regulatory Application to FDA for SKYRIZI® (risankizumab-rzaa) Subcutaneous Induction for Adults with Moderately to Severely Active Crohn's Disease - Apr 27, 2026news.abbvie.com
- Efficacy and safety of Mirikizumab for ulcerative colitis: a systematic review and meta-analysis of randomized controlled trialsbmcgastroenterol.biomedcentral.com
- Surgical interventions in inflammatory bowel disease: Indications, techniques, outcomes, and future directions - PubMedpubmed.ncbi.nlm.nih.gov
- Surgical interventions in inflammatory bowel disease: Indications, techniques, outcomes, and future directionsdoi.org
- 2-Stage and 3-stage restorative proctocolectomy with ileal pouch-anal anastomosis for ulcerative colitis show comparable short- and long-term outcomesncbi.nlm.nih.gov
- Ileal pouch-anal anastomosis for ulcerative colitis: 30-year analysis on surgical evolution and patient outcomencbi.nlm.nih.gov
- Ileal pouch–anal anastomosis in ulcerative colitis: outcomes, functional results, and quality of life in patients with more than 10-year follow-uplink.springer.com
- 2-Stage and 3-stage restorative proctocolectomy with ileal pouch-anal anastomosis for ulcerative colitis show comparable short- and long-term outcomesnature.com
- Functional outcomes following ileal pouch-anal anastomosis (IPAA) in older patients: a systematic reviewncbi.nlm.nih.gov
- Surgery for inflammatory bowel disease in the era of laparoscopy - PMCpmc.ncbi.nlm.nih.gov
- Surgery in Inflammatory Bowel Diseases (IBDs) Overview ...crohnscolitisfoundation.org
- Risk factors for surgical recurrence and the preventive effect of endoscopic balloon dilatation in postoperative patients with Crohn ‘s disease - PMCpmc.ncbi.nlm.nih.gov
- Cimzia Versus Mesalamine for Crohn's Recurrenceclinicaltrials.gov
- Postoperative Recurrence in Crohn’s Disease: Pathophysiology, Risk Stratification, and Management Strategiesncbi.nlm.nih.gov
- Risk Factors for Complications and Disease Recurrence after Ileocecal Resection for Crohn’s Disease in Children and Adultsncbi.nlm.nih.gov
- 1 IBD Surgery: Clinical Pearls for IBD Nurses and Advanced Providerscrohnscolitisfoundation.org
- Evaluating Quality of Life in Surgically Treated IBD Patients: A Systematic Review of Physical, Emotional and Social Impactsncbi.nlm.nih.gov
- Crohn's disease recurrence can be prevented after ileal resection - PMCpmc.ncbi.nlm.nih.gov
- Evaluating Quality of Life in Surgically Treated IBD Patients: A Systematic Review of Physical, Emotional and Social Impacts - PMCpmc.ncbi.nlm.nih.gov
- Crohn’s Disease Complications: Fistulas, Arthritis, and Morehealthline.com
- Practical Approach to Stricture Management in Crohn’s Disease - Practical Gastropracticalgastro.com
- Crohn Disease - Gastroenterology - Merck Manual Professional Editionmerckmanuals.com
- Crohn Disease Treatment & Management: Approach Considerations, Pharmacologic Therapy for Diarrhea, Anti-inflammatory and Immunosuppressant Therapy for Active Crohn Diseaseemedicine.medscape.com
- Can you die from Crohn's disease? Risks and complicationsmedicalnewstoday.com
- Severe Sepsis Secondary to Toxic Megacolon Revealing an Inflammatory Bowel Diseasencbi.nlm.nih.gov
- Complications of IBDcrohnsandcolitis.org.au
- Colorectal cancer surveillance in inflammatory bowel disease: Practice guidelines and recent developmentswjgnet.com
- Advancing Colorectal Cancer Prevention in Inflammatory Bowel Disease (IBD): Challenges and Innovations in Endoscopic Surveillancencbi.nlm.nih.gov
- Predicting Colorectal Cancer Occurrence in IBDncbi.nlm.nih.gov
- Endoscopic surveillance and management of colorectal dysplasia in inflammatory bowel diseases (IBD)gastro.org
- Inflammatory Bowel Disease and Colorectal Cancer: Epidemiology, Etiology, Surveillance, and Management - PMCpmc.ncbi.nlm.nih.gov
- From random to precise: updated colon cancer screening and surveillance for inflammatory bowel disease - Fatakhova - Translational Gastroenterology and Hepatologytgh.amegroups.org
- Vitamin and mineral deficiencies in inflammatory bowel disease - UpToDateuptodate.com
- Thrombosis and Anemia in Pediatric Inflammatory Bowel Disease: Pathophysiology, Clinical Impact and Future Directions - PMCpmc.ncbi.nlm.nih.gov
- Malnutrition in Patients with Inflammatory Bowel Disease (IBD)acute.org
- Venous thromboembolism in patients with inflammatory bowel disease: Focus on prevention and treatmentwjgnet.com
- Crohn’s Disease Complications and When to See a Doctorresources.healthgrades.com
- Colorectal cancer screening and surveillance in patients with inflammatory bowel disease in 2021 - PMCpmc.ncbi.nlm.nih.gov
- Surveillance and management of colorectal dysplasia and cancer in inflammatory bowel disease: Current practice and future perspectives - ScienceDirectsciencedirect.com
- Common Micronutrient Deficiencies in IBDcrohnscolitisfoundation.org
- Guidelines for the management of growth failure in childhood inflammatory bowel disease - PubMedpubmed.ncbi.nlm.nih.gov
- Growth retardation in early-onset inflammatory bowel disease: should we monitor and treat these patients differently? - PubMedpubmed.ncbi.nlm.nih.gov
- Growth, puberty, and bone health in children and adolescents with inflammatory bowel diseasebmcpediatr.biomedcentral.com
- Conception, pregnancy and inflammatory bowel disease—Current concepts for the practising clinician - PMCpmc.ncbi.nlm.nih.gov
- Pregnancy in Patients with Inflammatory Bowel Disease: A Narrative Review - PMCpmc.ncbi.nlm.nih.gov
- [Inflammatory bowel disease and pregnancy] - PubMedpubmed.ncbi.nlm.nih.gov
- Prevalence of Anxiety and Depression in Patients with Inflammatory Bowel Diseasencbi.nlm.nih.gov
- Depression and anxiety in patients with Inflammatory Bowel Disease: A systematic review - ScienceDirectsciencedirect.com
- [Prevalence of Anxiety and Depression in Patients with Inflammatory Bowel Disease: Association with Disease Activity and its Impact on Quality of Life] - PubMedpubmed.ncbi.nlm.nih.gov
- Prevalence of symptoms of anxiety and depression in patients with inflammatory bowel disease: a systematic review and meta-analysis - ScienceDirectsciencedirect.com
- Quality of Life in Patients With Inflammatory Bowel Disease: Importance of Psychological Symptoms - PMCpmc.ncbi.nlm.nih.gov
- Prevalence of Anxiety and Depression Symptoms Among Patients With Inflammatory Bowel Disease: A Multicenter Studyncbi.nlm.nih.gov
- Puberty and growth in patients with pediatric intestinal failure - ScienceDirectsciencedirect.com
- [Growth failure as a symptom of inflammatory bowel disease] - PubMedpubmed.ncbi.nlm.nih.gov
- Impact of Disease and Treatments on Growth and Puberty of Pediatric Patients with Inflammatory Bowel Diseasekarger.com
- Pregnancy outcomes among women with inflammatory bowel disease: A UK tertiary centre experience - PMCpmc.ncbi.nlm.nih.gov
- Inflammatory bowel disease in pregnancy - PMC - NIHpmc.ncbi.nlm.nih.gov
- Prevalence of Anxiety and Depression in Patients with Inflammatory Bowel Disease: Association with Disease Activity and its Impact on Quality of Life - PMCpmc.ncbi.nlm.nih.gov
- Prevalence of Anxiety and Depression Symptoms Among Patients With Inflammatory Bowel Disease: A Multicenter Study - PubMedpubmed.ncbi.nlm.nih.gov
- Full article: Burden of comorbid anxiety and depression in patients with inflammatory bowel disease: a systematic literature reviewtandfonline.com
- A Look Back at Our Beginningcrohnscolitisfoundation.org
- Where was Crohn's colitis in 1932? - PubMedpubmed.ncbi.nlm.nih.gov
- Montreal classification of inflammatory bowel diseaseradiopaedia-org.translate.goog
- Infliximab Approved for Use in Crohn's Disease: A Report on the FDA GI Advisory Committee Conferenceacademic.oup.com
- Infliximaben.wikipedia.org
- Switching Between Biologics and Biosimilars in Inflammatory Bowel Disease - Clinical Gastroenterology and Hepatologycghjournal.org
- Crohn's disease • LITFL • Medical Eponym Librarylitfl.com
- Is Crohn's disease a rightly used eponym? Philippe Van Hootegem, MD, FEBGHora.ox.ac.uk
- A brief history of ulcerative colitis - Hektoen Internationalhekint.org
- The Secret History of Crohn’s Diseasehistorycooperative.org
- Infliximab in Crohn’s disease: first anniversary clinical experience - ScienceDirectsciencedirect.com
- Remicade (infliximab) FDA Approval History - Drugs.comdrugs.com
- Remicade® (infliximab): 20 years of contributions to science and medicine - PMCpmc.ncbi.nlm.nih.gov
- Immune Reconstitution After Autologous Hematopoietic Stem Cell Transplantation in Crohn’s Disease: Current Status and Future Directions. A Review on Behalf of the EBMT Autoimmune Diseases Working Party and the Autologous Stem Cell Transplantation In Refractory CD—Low Intensity Therapy Evaluation Study Investigatorsncbi.nlm.nih.gov
- Autologous Hematopoetic Stem Cell Transplantation for Refractory Crohn Disease: A Randomized Clinical Trialjamanetwork.com
- Autologous Hematopoetic Stem Cell Transplantation for Refractory Crohn Disease: A Randomized Clinical Trial - PubMedpubmed.ncbi.nlm.nih.gov
- (PDF) Autologous hematopoietic stem cell transplantation for refractory Crohn's diseaseresearchgate.net
- Engineering immune cell therapies for inflammatory bowel disease: from stem cells to CAR T cellsnature.com
- Case Report: IBD-like colitis following CAR T cell therapy for diffuse large B cell lymphomancbi.nlm.nih.gov
- CAR-T cells and CAR-Treg cells for treatment of inflammatory bowel diseases - PubMedpubmed.ncbi.nlm.nih.gov
- Flagellin-specific human CAR Tregs for immune regulation in IBD - ScienceDirectsciencedirect.com
- Frontiersfrontiersin.org
- Effect of Fecal Microbiota Transplantation on 8-Week Remission in Patients With Ulcerative Colitis: A Randomized Clinical Trialjamanetwork.com
- Efficacy of Fecal Microbiota Transplantation in the Treatment of Active Ulcerative Colitis: A Systematic Review and Meta-Analysis of Double-Blind Randomized Controlled Trialsacademic.oup.com
- Fecal microbiota transplantation for patients with ulcerative colitis: a systematic review and meta-analysis of randomized control trialsncbi.nlm.nih.gov
- Efficacy and safety of autologous hematopoietic stem cell therapy for refractory Crohn's disease: A systematic review and meta-analysis - PubMedpubmed.ncbi.nlm.nih.gov
- CAR-T cell therapy treats severe bowel disease successfully for the first timefau.eu
- CAR-T cells and CAR-Treg cells for treatment of inflammatory bowel diseases - PMCpmc.ncbi.nlm.nih.gov
- Opportunities and challenges harnessing antigen-specific CD4+ regulatory T cells in inflammatory bowel diseasencbi.nlm.nih.gov
- Biobetters and biosimilars in inflammatory bowel disease - ScienceDirectsciencedirect.com
- Biosimilars for the Treatment of Inflammatory Bowel Disease - PMCpmc.ncbi.nlm.nih.gov
- Benefits of Biosimilars in the Management of Patients with Inflammatory Bowel Disease: An International Surveyncbi.nlm.nih.gov
- Impact of biosimilars on the costs of advanced therapies for inflammatory bowel diseases: a population-based study in Italy - PubMedpubmed.ncbi.nlm.nih.gov
- Biological Therapies in Immune-Mediated Inflammatory Diseases: Can Biosimilars Reduce Access Inequities?ncbi.nlm.nih.gov
- Disparities in Access and Treatment for Rural Patients With Inflammatory Bowel Disease: A Survey of Inflammatory Bowel Disease Patients and Providers - PMCpmc.ncbi.nlm.nih.gov
- Inequities in Rural and Urban Health Care Utilization Among Individuals Diagnosed With Inflammatory Bowel Disease: A Retrospective Population-Based Cohort Study From Saskatchewan, Canadaacademic.oup.com
- Equitable access to inflammatory bowel disease care: challenges, strategies, and future directionsacademic.oup.com
- Controversies in the treatment of Crohn’s disease: The case for an accelerated step-up treatment approachdoi.org
- Early 'top-down' therapy reduces Crohn's disease complicationsnews.gastro.org
- Long-term outcomes of top-down therapy versus a conventional step-up strategy in adults newly diagnosed with Crohn's disease: 5-year follow-up of the PROFILE trial - ScienceDirectsciencedirect.com
- A biomarker-stratified comparison of top-down versus accelerated step-up treatment strategies for patients with newly diagnosed Crohn's disease (PROFILE): a multicentre, open-label randomised controlled trialncbi.nlm.nih.gov
- Early Thiopurines Versus Conventional Step-Care Therapy for Modifying the Disease Course of Early Crohn's Disease: A Tertiary Referral Center Cohort Studyncbi.nlm.nih.gov
- Integration of Ustekinumab Biosimilars into Inflammatory Bowel Disease Care: Evidence, Implementation, and Patient-Centered Considerations - PMCpmc.ncbi.nlm.nih.gov
- Inequalities in Healthcare Access, Experience and Outcomes in Adults With Inflammatory Bowel Disease: A Scoping Reviewdoi.org
- Who bears the brunt? Geographic, racial and ethnic disparities in mortality trends of inflammatory bowel disorders in the United Statescambridge.org