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Corrigendum: PACSIN2 Does Not Influence Thiopurine-Related Toxicity in Patients With Inflammatory Bowel Disease

Introduction Pancreatitis is a rare, but important complication of thiopurine treatment. The aims of this project were to a) characterise the clinical features of thiopurine-induced pancreatitis and b) identify clinical useful genetic markers that might predict development of this serious adverse drug reaction. Methods Patients were identified and recruited from 172 sites (128 UK). Inclusion criteria included a) onset of acute severe abdominal pain within three months of starting thiopurine treatment b) ≥ two-fold rise in amylase or lipase c) medical opinion implicating thiopurine therapy and drug withdrawal. Results We recruited 303 patients. Following adjudication 48 cases classified as definite (recurrent pancreatitis on rechallenge) and 195 cases classified as probable (temporal relationship and no other cause for pancreatitis) were taken forward for analyses. 46% of patients were smokers at the time of development of pancreatitis. Patients were treated with a thiopurine for a median of 19 days (95% CI: 17 – 21) before development of pancreatitis. Most cases were mild, with only 5 cases developing single organ dysfunction. 70% of patients were hospitalised with a median length of stay of 4 days (95% CI: 3.2 – 4.8). Neither age (p = 0.08), drug dose (p = 0.11), BMI (p = 0.73) nor smoking (p = 0.59) predicted length of hospital stay or severity of pancreatitis in multivariate analysis. Using a control cohort of 4,109 Crohn’s disease and ulcerative colitis cases we conducted a genome wide association study with these 239 patients. A significant variant was identified in the Class II MHC region (Odds ratio 3.03, p = 2.63 × 10–20). Dedicated HLA and 1000 genome project imputation refined the association within the MHC (R squared > 0.8 and MAF > 0.01). This association was robust to principle component correction. TPMT genotype was not associated with pancreatitis development (p = 0.99). A second cohort of 100 cases and 500 independent disease controls treated with thiopurines but screened for pancreatitis has been generated to confirm the association. Conclusion We describe the largest clinical characterisation of thiopurine-induced pancreatitis to date and use this cohort to undertake a pharmacogenetics genome wide association study that has identified a significant association within the Class II MHC region. Disclosure of Interest None Declared.

To elucidate the biological dysregulation underlying two forms of inflammatory bowel disease (IBD), ulcerative colitis (UC) and Crohn's disease (CD), we examined global gene expression profiles of inflamed colonic tissue using DNA microarrays. Our results identified several genes with altered expression not previously linked to IBD. In addition to the expected upregulation of various cytokine and chemokine genes, novel immune function-related genes such as IGHG3, IGLL2 and CD74, inflammation-related lipocalins HNL and NGAL, and proliferation-related GRO genes were over-expressed in UC. Certain cancer-related genes such as DD96, DRAL and MXI1 were differentially expressed only in UC. Other genes over-expressed in both UC and CD included the REG gene family and the calcium-binding S100 protein genes S100A9 and S100P. The natural antimicrobial defensin DEFA5 and DEFA6 genes were particularly over-expressed in CD. Overall, significant differences in the expression profiles of 170 genes identified UC and CD as distinct molecular entities. The genomic map locations of the dysregulated genes may identify novel candidates for UC and CD genetic susceptibility.

The inflammatory bowel diseases (IBDs) are chronic incurable conditions that primarily present in young patients. Being incurable, the IBDs may be part of the patient's life for many years and these conditions require therapies that will be effective over the long-term. Surgery in Crohn's disease does not cure the disease with endoscopic recurrent in up to 70% of patients 1 year post resection. This means that, the patient will require many years of medications and the goal of the treating physician is to induce and maintain long-term remission without side effects. The development of the anti-tumour necrosis factor alpha (TNFα) agents has been a magnificent clinical advance in IBD, but they are not always effective, with loss of response overtime and, at times, discontinuation is required secondary to side effects. So what options are available if of the anti-TNFα agents can no longer be used? This review aims to provide other options for the physician, to remind them of the older established medications like azathioprine/6-mercaptopurine and methotrexate, the less established medications like mycophenolate mofetil and tacrolimus as well as newer therapeutic options like the anti-integins, which block the trafficking of leukocytes into the intestinal mucosa. The location of the intestinal inflammation must also be considered, as topical therapeutic agents may also be worthwhile to consider in the long-term management of the more challenging IBD patient. The more options that are available the more likely the patient will be able to have tailored therapy to treat their disease and a better long-term outcome.

Introduction Nephrotoxicity is a rare idiosyncratic reaction to 5-ASA therapy. The precise pathogenic mechanisms are unknown. This study aims to a) describe the clinical features of this rare complication b) explore underlying mechanisms and c) identify clinically useful predictive genetic markers so these drugs can be avoided, or monitoring intensified, in high-risk patients. Here we report the clinical features. Methods Patients were identified and recruited from 185 sites (130 UK). Inclusion criteria included normal renal function prior to commencing 5-ASA, ≥50% rise in creatinine after starting 5-ASA and medical opinion implicating 5-ASA justified drug withdrawal. An adjudication panel assessed causality from case report forms using the validated Liverpool Adverse Drug Reaction Causality Assessment Tool. Results 154 patients were recruited. 19 patients were excluded following adjudication. The cohort included patients with Crohn’s disease, ulcerative colitis and indeterminate colitis (42%, 55%, 4% respectively). 74% of cases were male. Nephrotoxicity was seen with all aminosalicylates including 1 patient treated with topical therapy only. Nephrotoxicity occurred at a median age of 36.5 yrs (range 15.4–88.4 yrs). Two patients had a confirmed family history of 5-ASA-induced nephrotoxicity. 78% were detected by routine blood monitoring. Only 45% of cases recovered completely after drug withdrawal, with 18 requiring renal replacement therapy (14 transplantation). The median time for peak creatinine after commencing 5-ASA was 3.5 yrs (range 0.16–43.4 yrs). There was no evidence that time on 5-ASA treatment was associated with a higher peak creatinine or the likelihood of full recovery (p = 0.87). Women were more likely to reach full recovery than men (p = 0.00148; OR 8.26; CI 2.46–34.94). There was no evidence that early withdrawal of 5-ASA led to a higher likelihood of complete recovery. There was no difference in recovery between the three disease groups on logistic regression analysis. Conclusion This is the largest and most detailed study of 5-ASA induced nephrotoxicity to date. Whilst the incidence is low, the morbidity is high with 13% of patients requiring renal replacement therapy and 55% of patients failing to return to a normal creatinine after 5-ASA withdrawal. The next step is to carry forward these patients to a genome-wide association analysis, to be performed in February 2013. Disclosure of Interest None Declared

Clinical and molecular characterization of medically refractory acute, severe colitis : preliminary results from the international inflammatory bowel disease genetics consortium (IIBDGC) immunochip study

G A A b st ra ct s ulcerations at ileocolonoscopy and a history of positive clinical response followed by secondary failure and/or intolerance to at least one TNFα antagonist. Patients randomized in the TNF-K group were receiving TNF-K at days 0, 7, 28, 84 and placebo at days 91 and 112. Patients randomized in the control group were receiving placebo at days 0, 7, 28, and TNFK at days 84, 91 and 112. TNF-K was injected intramuscularly at the dose of 180 mcg per injection. The primary end point was CDAI clinical remission (CDAI≤150) at week 8. Other efficacy end-points included mucosal healing at week 12 and evolution of calprotectin and C-reactive protein. Immune responses were evaluated through titration of anti-TNFα and anti-KLH antibodies. Results: All patients have been recruited. Fewmild or moderate transient local and systemic reactions have been recorded following immunizations. The only serious adverse event reported by the investigator as potentially related to the study drug was a deterioration of CD one month following administration of blinded treatment. There were no other safety concerns. Full analysis is ongoing. Conclusions: Active immunization with TNF-K in patients with Crohn's disease is safe. Full immunogenicity and clinical efficacy results will be presented.

Predicting Long-Term Response to Anti-TNF Therapy in Crohn's Disease Graham Radford-Smith, Felicity Hartnell, Lee V. Jones, Krupa Krishnaprasad, Ruth Prosser, Debbie Marr, Rachel Grafton, Sharon E. Cooke, Jesse Fischer, Gareth R. Thomas, Zubin Grover, Peter Lewindon, Jane V. Tehan, Nik S. Ding, Kerrie Moss, Sally Bell, Peter De Cruz, Gillian Mahy, Karen Sewell, Anthony Croft, Peter O'Rourke, Ian C. Lawrance, Peter A. Bampton, Jane M. Andrews, Richard B. Gearry

Background: Colorectal cancer (CRC) is common, but human sporadic and colitis-associated CRC (CAC) have different pathogeneses. The aim of this study was to identify differences in gene expression levels and inflammatory cell infiltration of tumours from mice models of sporadic and CAC. Methods: Mice used in this study are on a FVB background. Sporadic CRC tumourigenesis was mimicked by giving 6 weekly intraperitoneal (IP) injections of azoxymethane (AOM). CAC was modelled by a single AOM IP injection prior to two cycles of 7 days of dextran sodium sulphate (DSS) in the drinking water followed by 14 days of plain water. Tumours of similar size were harvested from both models at weeks 13 (AOM-alone) and 8 (AOM/DSS) respectively and processed for further analysis. Histological and immunofluorescent (IF) assessment of CD4, CD8a, F4/80, and Ly6G was performed on tumours. Wholegenome microarray (Illumina BeadChip, MouseRef 8 v2) was used to compare gene expression in tumours from both models. Gene ontology analysis was performed using the Database for Annotation, Visualisation and Integrated Discovery. Results: The majority of tumours were polypoid and all were dysplastic. Unlike AOM/DSS, the AOM-alone protocol induced high-grade dysplasic polyps (21% [4/19] vs 0% [0/9]) and 2 flat lesions, one with invading CRC. Microarray analysis identified that 665 genes were differentially expressed between the tumours (p < 0.05), and 398 had increased expression levels in the AOM-alone tumours and included genes associated with cytokine activity, cell division, and the regulation of apoptosis. 267 genes were reduced and were associated with immune response, the lysosome and positive regulation of the immune system. IF assessment of the inflammatory cell infiltrates showed the presence of CD4-positive, CD8a-positive, F4/80-positive and Ly6G-positive cells in all tumours without any significant differences in the cell numbers between the models. Conclusions: AOM and AOM/DSS tumours are histologically different with marked gene-expression differences suggesting a different pathogenesis. All AOM-alone tumours displayed inflammatory cell infiltration suggesting a crucial role for the immune cells in the progression of tumours in both models once tumourigenesis is initiated. Further work is required to confirm histological differences between AOM and AOM/DSS tumours.

findings. Endoscopic activity was classified as active and quiescent disease, based on the endoscopic Mayo Subscore (UC) and SES-CD (CD) index. In cases with active disease, biopsies were taken from both endoscopically affected and non-affected mucosa. Following pathologist’s criteria, biopsies were classified as normal, affected mucosa, unspecific inflammation, and quiescent. Results: 67 biopsies from 52 patients with histological diagnosis of IBD (31 UC and 21 EC) and 19 from subjects without IBD were studied. 38.6% cases had active disease. MV count was lower in samples from patients without IBD (Table 1; p < 0.0001), even when comparing only normal mucosa. Patients with UC showed the highest count of Ang1+MV in both cases (Table 2). MV density was also increased in samples with endoscopic activity (52.3±19.5 vs 41.7±15.8; P= 0.02) but it did not correlate with histology.

Background: Colorectal cancer (CRC) is common, but human sporadic and colitis-associated CRC (CAC) have different pathogeneses. The aim of this study was to identify differences in gene expression levels and inflammatory cell infiltration of tumours from mice models of sporadic and CAC. Methods: Mice used in this study are on a FVB background. Sporadic CRC tumourigenesis was mimicked by giving 6 weekly intraperitoneal (IP) injections of azoxymethane (AOM). CAC was modelled by a single AOM IP injection prior to two cycles of 7 days of dextran sodium sulphate (DSS) in the drinking water followed by 14 days of plain water. Tumours of similar size were harvested from both models at weeks 13 (AOM-alone) and 8 (AOM/DSS) respectively and processed for further analysis. Histological and immunofluorescent (IF) assessment of CD4, CD8a, F4/80, and Ly6G was performed on tumours. Wholegenome microarray (Illumina BeadChip, MouseRef 8 v2) was used to compare gene expression in tumours from both models. Gene ontology analysis was performed using the Database for Annotation, Visualisation and Integrated Discovery. Results: The majority of tumours were polypoid and all were dysplastic. Unlike AOM/DSS, the AOM-alone protocol induced high-grade dysplasic polyps (21% [4/19] vs 0% [0/9]) and 2 flat lesions, one with invading CRC. Microarray analysis identified that 665 genes were differentially expressed between the tumours (p < 0.05), and 398 had increased expression levels in the AOM-alone tumours and included genes associated with cytokine activity, cell division, and the regulation of apoptosis. 267 genes were reduced and were associated with immune response, the lysosome and positive regulation of the immune system. IF assessment of the inflammatory cell infiltrates showed the presence of CD4-positive, CD8a-positive, F4/80-positive and Ly6G-positive cells in all tumours without any significant differences in the cell numbers between the models. Conclusions: AOM and AOM/DSS tumours are histologically different with marked gene-expression differences suggesting a different pathogenesis. All AOM-alone tumours displayed inflammatory cell infiltration suggesting a crucial role for the immune cells in the progression of tumours in both models once tumourigenesis is initiated. Further work is required to confirm histological differences between AOM and AOM/DSS tumours.

Nat. Genet. 43, 246–252 (2011); published online 6 February 2011; corrected after print 11 August 2011 In the version of this article initially published, an affiliation was missing for two authors, Maria Gazouli and Nicholas P. Anagnou. They are also affiliated with the Foundation for Biomedical Research of the Academy of Athens in Athens, Greece.

BACKGROUND: SPARC is a matricellular protein involved in tissue remodelling, cell migration and angiogenesis, while forkhead box P3 (FOXP3) protein functions as a transcription factor involved in immune cell regulation. Both SPARC and FOXP3 can play an anti-tumorigenic role in cancer progression. The aim was to determine if SPARC, FOXP3, CD8 and CD45RO expression levels are associated with colorectal cancer (CRC) stage, disease outcome and long-term cancer-specific survival (CSS) in stage II and III CRC. METHODS AND FINDINGS: SPARC expression was initially assessed in 120 paired normal and stage I-IV CRCs. Subsequently, approximately 1000 paired patient samples of stage II or III CRCs in tissue microarrays were stained for SPARC, FOXP3, CD8 or CD45RO. Proportional hazards modelling assessed correlations between these markers and clinicopathological data, including disease outcome and cancer specific survival (CSS). Both SPARC and FOXP3 expression were significantly greater in CRC than normal colon (p

Purpose To assess remission rates in patients who received certolizumab pegol for 6 months (26 weeks) in PRECiSE 2, and for a further 4.5 years in PRECiSE 3, and to determine if remission rates are affected in patients without previous tumor necrosis factor (TNF) inhibitor exposure. Methods Patients completing PRECiSE 2 (NCT00152425) were eligible to enter PRECiSE 3 (NCT00160524) and receive certolizumab pegol 400 mg every 4 weeks. Efficacy and safety data for patients who received certolizumab pegol in PRECiSE 2 and continued with open-label certolizumab pegol treatment in PRECiSE 3 are presented. The HarveyBradshaw Index (HBI) was used to measure disease activity (remission = score of ≤4). Remission rates were analyzed from the baseline of PRECiSE 2 in the PRECiSE 3 ITT population and in a subset of this population who had never received infliximab (IFXnaive). Remission rates were calculated using observed case analyses and nonresponder imputation (NRI). Results Of the 141 patients in the PRECiSE 3 population, 114 were IFXnaive. At the start of PRECiSE 3 (Week 0), 75% (105/141) and 78% (89/114) of the total and IFX-naive populations were in remission, respectively. Remission rates for the total PRECiSE 3 population after 1, 2, 3, 4, and 5 years (observed case) were 75%, 84%, 82%, 79%, and 91%, respectively, and 76%, 83%, 82%, 81%, and 89%, respectively, for the IFXnaive patients (Table). Remission rates for the total PRECiSE 3 population after 1, 2, 3, 4, and 5 years (NRI) were 65%, 49%, 35%, 23%, and 21%, respectively, and 65%, 47%, 37%, 25%, and 21%, respectively, for the IFX-naive patients. No new safety signals were observed and there were no unexpected serious adverse events. Conclusions Among patients who initially responded to certolizumab pegol induction therapy and remained in PRECiSE 3, continuous certolizumab pegol 400 mg therapy provided long-term remission for 5 years, including a subset of PRECiSE 3 patients receiving certolizumab pegol with no previous exposure to infliximab.

BACKGROUND: Certolizumab pegol (CZP) is a PEGylated anti-TNF-α therapy that was effective at inducing fistula closure in a post-hoc analysis of the 26-week open-label induction and double-blind maintenance study in Crohn's disease (CD) (PRECiSE 2 [P2], NCT00152425). OBJECTIVE: We now report 3-year data for maintenance of response and remission in the subpopulation of P2 patients with fistulizing CD who continued to receive open-label CZP (PRECiSE 3 [P3] extension study, NCT00160524). METHODS: Patients enrolled in P2 received open-label induction at Weeks 0, 2, and 4 with subcutaneous CZP 400 mg. Responders (≥100-point reduction from baseline in CD Activity Index [CDAI] at Week 6) were randomized to CZP 400 mg or placebo q4w and assessed at Week 26. Patients who completed P2 and entered P3 received open-label CZP 400 mg q4w. In P3, efficacy measures includedHarvey-Bradshaw Index (HBI) response (≥3-point decrease frombaseline) and remission (HBI ≤4). This analysis only included patients who had open fistulas at Week 0 of P2. Fistula closure was defined as the absence of drainage on gentle compression in ≥50% of open fistulae at any 2 consecutive post-baseline visits at ≥3 weeks apart during the study. RESULTS: 58 patients in the intention-to-treat population of P2 who responded to CZP induction (13.6% of 425) had open fistulas at baseline: 30 were randomized to placebo and 28 to CZP 400 mg. Of these, 35 patients entered P3 (placebo n=14 and CZP 400 mg n=21 from P2). Fistula closure was observed in 52.4% (11/21) of patients assigned to CZP 400 mg compared with 42.9% (6/14) on placebo in P2. Of those in the active group in P2, response and remission rates were higher in patients with fistula closure than in patients with open fistula, and were maintained through to Week 154 of P3 (Table). CONCLUSIONS: Carry-over from open-label induction led to some fistula response under placebo during the maintenance phase of P2. Most former placebo patients had closed fistula after switching to open-label CZP 400 mg q4w. Long-term maintenance with CZP 400 mg q4w was efficacious at maintaining clinical response and remission in patients with fistulizing CD.

BACKGROUND: Certolizumab pegol (CZP) is a PEGylated anti-TNF-α therapy that was effective at inducing fistula closure in a post-hoc analysis of the 26-week open-label induction and double-blind maintenance study in Crohn's disease (CD) (PRECiSE 2 [P2], NCT00152425). OBJECTIVE: We now report 3-year data for maintenance of response and remission in the subpopulation of P2 patients with fistulizing CD who continued to receive open-label CZP (PRECiSE 3 [P3] extension study, NCT00160524). METHODS: Patients enrolled in P2 received open-label induction at Weeks 0, 2, and 4 with subcutaneous CZP 400 mg. Responders (≥100-point reduction from baseline in CD Activity Index [CDAI] at Week 6) were randomized to CZP 400 mg or placebo q4w and assessed at Week 26. Patients who completed P2 and entered P3 received open-label CZP 400 mg q4w. In P3, efficacy measures includedHarvey-Bradshaw Index (HBI) response (≥3-point decrease frombaseline) and remission (HBI ≤4). This analysis only included patients who had open fistulas at Week 0 of P2. Fistula closure was defined as the absence of drainage on gentle compression in ≥50% of open fistulae at any 2 consecutive post-baseline visits at ≥3 weeks apart during the study. RESULTS: 58 patients in the intention-to-treat population of P2 who responded to CZP induction (13.6% of 425) had open fistulas at baseline: 30 were randomized to placebo and 28 to CZP 400 mg. Of these, 35 patients entered P3 (placebo n=14 and CZP 400 mg n=21 from P2). Fistula closure was observed in 52.4% (11/21) of patients assigned to CZP 400 mg compared with 42.9% (6/14) on placebo in P2. Of those in the active group in P2, response and remission rates were higher in patients with fistula closure than in patients with open fistula, and were maintained through to Week 154 of P3 (Table). CONCLUSIONS: Carry-over from open-label induction led to some fistula response under placebo during the maintenance phase of P2. Most former placebo patients had closed fistula after switching to open-label CZP 400 mg q4w. Long-term maintenance with CZP 400 mg q4w was efficacious at maintaining clinical response and remission in patients with fistulizing CD.

Distal colitis (DC) can be effectively treated with topical 5ASA agents. Suppositories target the rectum while enemas can reliably reach the splenic flexure. Used in combination with oral 5ASAs, the control of the inflammation is even more effective. Unfortunately, resistant DC does occur and can be extremely challenging to manage. In these patients, the use of steroids, immunosuppressants and the anti-tumor necrosis factor α agents are often required. These, however, can be associated with systemic side effects and are not always effective. The investigation of new topical therapeutic agents is thus required as they are rarely associated with significant blood drug levels and side effects are infrequent. Some of the agents that have been proposed for use in resistant distal colitis include butyrate, cyclosporine and nicotine enemas as well as tacrolimus suppositories and tacrolimus, ecabet sodium, arsenic, lidocaine, rebamipide and Ridogrel(®) enemas. Some of these agents have demonstrated impressive results but the majority of the agents have only been assessed in small open-labelled patient cohorts. Further work is thus required with the investigation of promising agents in the context of randomized double-blinded placebo controlled trials. This review aims to highlight those potentially effective therapies in the management of resistant distal colitis and to promote interest in furthering their investigation.

The carcinogenic potential of iron in colorectal cancer (CRC) is not fully understood. Iron is able to undergo reduction and oxidation, making it important in many physiological processes. This inherent redox property of iron, however, also renders it toxic when it is present in excess. Iron-mediated generation of reactive oxygen species via the Fenton reaction, if uncontrolled, may lead to cell damage as a result of lipid peroxidation and oxidative DNA and protein damage. This may promote carcinogenesis through increased genomic instability, chromosomal rearrangements as well as mutations of proto-oncogenes and tumour suppressor genes. Carcinogenesis is also affected by inflammation which is exacerbated by iron. Population studies indicate an association between high dietary iron intake and CRC risk. In this editorial, we examine the link between iron-induced oxidative stress and inflammation on the pathogenesis of CRC.

for the oral sulfate solution and the PEG-EA regimen, respectively. Split dose administration resulted in more excellent preparations in the sulfate group than in the PEG-EA group (63.3% vs 52.5%, P=0.043), and a higher mean preparation score (3.59 to 3.47, respectively, P=0.05). Preparation related symptoms of cramping, bloating, nausea and vomiting were generally mild and infrequent. Sulfate subjects reported slightly increased gastrointestinal events and higher vomiting scores (p = 0.009) in the one day preparation but not in the split dose regimen. There were no other differences for adverse events or clinically significant laboratory findings including creatinine. Conclusion: The new 960ml oral sulfate solution is effective for colonoscopy cleansing and has an acceptable safety profile. Split-dose administration provided additional efficacy and tolerance.

The anti-tumor necrosis factor (TNF)alpha medications demonstrate efficacy in the induction of remission and its maintenance in numerous chronic inflammatory conditions. With the increasing number of patients receiving anti-TNFalpha agents, however, less common adverse reactions will occur. Cutaneous eruptions complicating treatment with an anti-TNFalpha agent are not uncommon, occurring in around 20% of patients. Adalimumab, a fully humanized antibody against TNFalpha, may be expected to cause minimal immune-mediated skin reactions compared to the chimeric monoclonal antibody, infliximab. We, however, report a case of Stevens-Johnson syndrome that required hospitalization and cessation of adalimumab in a patient with Crohn's disease (CD). In this case report, a 29-year-old male with colonic and perianal CD with associated erythema nodosum and large joint arthropathy developed severe mucositis, peripheral rash and desquamation, fevers and respiratory symptoms concomitant with a second dose of 40 mg adalimumab after a 2 mo break from adalimumab therapy. Skin biopsies of the abdominal wall confirmed erythema multiforme and the patient was on no other drugs and infective etiologies were excluded. The patient responded rapidly to IV hydrocortisone and was able to be commenced on infliximab without recurrence of the Stevens-Johnson syndrome. Desquamating skin reactions have now been described in three of the TNFalpha antagonists (infliximab, etanercept and adalimumab). These reactions can be serious and prescribers need to be aware of the potential mucocutaneous side effects of these agents, especially as Stevens-Johnson syndrome is associated with significant morbidity and mortality.

AIM: To determine whether magnetic resonance imaging (MRI) can be used to categorize small bowel Crohn’s disease (SB CD) into groups that correlate with response to medical therapy and surgical pathology. METHODS: Data was collected from all patients with MRI evidence of SB CD without significant colonic disease over a 32-mo period. Two radiologists, blinded to clinical findings, evaluated each MRI and grouped them based on bowel wall thickness and wall enhancement. These categories were: (1) “fibrosis”, (2) “mild segmental hyper-enhancement and mild wall thickening”, (3) “mild segmental hyper-enhancement and marked wall thickening”, (4) “marked segmental transmural hyper-enhancement”. Patient response to additional medical therapy post-MRI was prospectively determined at 8-wk. Non-responders underwent endoscopy and were offered therapeutic endoscopy or surgery. Surgical pathology was assessed against the MRI category. RESULTS: Fifty-five patients were included. Females and category “2” patients were more likely, and patients with luminal narrowing and hold-up less likely, to respond to medical therapy (P < 0.05). Seventeen patients underwent surgery. The surgical pathological findings of fibrosis and the severity of inflammation correlated with the MRI category in all cases. CONCLUSION: Our findings suggest that SB CD can be grouped by the MRI findings and that these groups are associated with patients more likely to respond to continued medical therapy. The MRI categories also correlated with the presence and level of intestinal inflammation and fibrosis on surgical pathology, and may be of prognostic use in the management of CD patients.