Decreased Infliximab Concentrations in Patients With Inflammatory Bowel Disease Who Carry a Variable Number Tandem Repeat Polymorphism in the Neonatal Fc Receptor or Variant HLADQA1*05G>A Genotype.

BACKGROUND: Multiple variables contribute to variation in patient exposure and response to tumor necrosis factor alpha antagonist biologics such as infliximab. This study aimed to assess the association between maintenance-phase infliximab concentrations and genetic variation in HLADQA1*05G>A and fragment crystallisable (Fc) fragment of IgG receptor and transporter (FCGRT) among patients with inflammatory bowel disease. METHODS: A cross-sectional study was carried out in participants with inflammatory bowel disease prescribed infliximab who were in the maintenance phase of treatment. Participants were genotyped for the presence of the FCGRT variable number tandem repeat (VNTR) and HLADQA1*05G>A (rs74291249). A point estimate of the infliximab trough concentration during the maintenance phase was determined using a standard enzyme-linked immunosorbent assay for each patient. Other variables associated with infliximab pharmacokinetics were collected. RESULTS: A total of 156 participants with inflammatory bowel disease were included from 2 tertiary care centers affiliated with Western University, London, Canada. Median infliximab trough concentrations were lower in participants who carried the FCGRT VNTR 2/3 or 2/2 (4.14 µg/mL; interquartile range [IQR], 6.48 µg/mL) vs wild type individuals (7.00 µg/mL; IQR, 7.66; P = .0027). Median infliximab trough concentrations were significantly lower in participants who were HLADQA1*05G>A variant carriers (4.73µg/mL; IQR, 4.79) vs wild type individuals (7.85µg/mL; IQR, 7.44; P = .0006). A significant decrease in infliximab trough concentrations was seen in individuals who were dual carriers of variant polymorphisms in HLADQA1*05G>A and FCGRT VNTR (no variants, 8.96µg/mL; IQR, 6.84 vs one variant, 4.96 µg/mL; IQR, 4.95 vs dual variants, 0.86µg/mL; IQR, 5.82). CONCLUSION: FCGRT VNTR and HLADQA1*05G>A are associated with lower maintenance-phase infliximab concentrations, particularly among patients who carry both variants.

HLADQA1*05G>A and FCGRT VNTR are associated with lower maintenance-phase infliximab concentrations, particularly among patients who carry both variants.

Use of topical mineral powder as monotherapy for treatment of active peptic ulcer bleeding.

BACKGROUND AND AIMS: The aim of this study was to evaluate the safety and effectiveness of Hemospray (Cook Medical, Winston-Salem, NC, USA), a hemostatic powder, as monotherapy for active peptic ulcer bleeding. METHODS: In this prospective, multicenter, single-arm study, patients with Forrest Ia or Ib peptic ulcers underwent endoscopic application of Hemospray as treatment of first intent. Effectiveness endpoints were successful hemostasis at the end of the index endoscopy, recurrent bleeding within 72 hours and from 72 hours to 30 days, adverse events requiring reintervention or resulting in morbidity or mortality, and 30-day mortality. RESULTS: Hemospray was successfully administered in 98.5% of patients (66/67). Hemostasis was achieved at the index endoscopy in 90.9% of patients (60/66) with Hemospray alone and in an additional 4 patients treated with additional modalities, yielding an overall hemostasis rate of 97.0% (64/66). Rebleeding occurred in 13.3% of patients (8/60), 5 within 72 hours and 3 between 72 hours and 30 days. Two cases of perforation and 2 patient deaths occurred during the study, but none of these cases or any other adverse events were attributed to the use of Hemospray. The rate of early rebleeding was significantly higher in patients with Forrest Ia ulcers compared with patients with Forrest Ib ulcers. Higher rates of early bleeding in patients with Forrest Ia ulcers is consistent with results from studies where Hemospray was used as rescue after failure of conventional methods. CONCLUSIONS: Hemospray is an effective initial treatment for patients with active peptic ulcer bleeding, but care should be taken to monitor for recurrent bleeding. (Clinical trial registration number: NCT01306864.).

High oncostatin M predicts lack of clinical remission for patients with inflammatory bowel disease on tumor necrosis factor α antagonists.

The interleukin-6 family cytokine, oncostatin-M (OSM) has been associated with response to tumor necrosis factor-α antagonists (anti-TNFs) in small cohorts of patients with inflammatory bowel disease (IBD). We aimed to evaluate the association between plasma OSM concentrations and response to anti-TNFs (infliximab and adalimumab) in both ulcerative colitis (UC) and Crohn's disease (CD). A retrospective cohort study was conducted in patients with IBD with a history of anti-TNF exposure. Blood samples, collected prior to anti-TNF exposure, were analyzed by enzyme-linked immunosorbent assay for the presence and quantity of OSM. Clinical remission was assessed at 1-year post anti-TNF exposure in addition to the occurrence of surgery, hospitalization, corticosteroid use, and adverse drug events. Lastly the threshold OSM plasma concentration associated with anti-TNF non-response was assessed by receiver operator characteristic (ROC) curve analysis. Patients with IBD (CD, n = 82; UC, n = 40) were assessed. In both UC and CD, mean pre-treatment OSM concentrations were significantly lower in those who achieved clinical remission at 1-year (p < 0.0001). A threshold plasma OSM concentration of 168.7 pg/ml and 233.6 pg/ml respectively separated those who achieved clinical remission at 1-year on an anti-TNF from those who did not in CD and UC respectively (CD: area under the receiver operator characteristic curve, AUROC = 0.880, 95% CI 0.79-0.96; UC: AUROC = 0.938, 95% CI 0.87-1.00). High OSM concentrations were associated with anti-TNF discontinuation and use of rescue steroids in CD and UC. High pre-treatment OSM concentrations identify IBD patients at-risk of anti-TNF non-response at 1-year as well as other deleterious clinical outcomes.

Pretreatment HLADQA1-HLADRB1 Testing for the Prevention of Azathioprine-Induced Pancreatitis in Inflammatory Bowel Disease: A Prospective Cohort Study.

INTRODUCTION: Azathioprine-induced pancreatitis is an idiosyncratic and unpredictable response, occurring in up to 7% of azathioprine-exposed patients with inflammatory bowel disease (IBD). The haplotype HLADQA1-HLADRB1*07:01A>C is strongly associated with azathioprine-induced pancreatitis in IBD. We aimed to evaluate whether pretreatment HLADQA1-HLADRB1*07:01A>C screening will reduce the risk of azathioprine-induced pancreatitis. METHODS: Participants with IBD were screened for HLADQA1-HLADRB1*07:01A>C, and participants with a variant genotype were excluded from azathioprine treatment. Wild-type participants were started on azathioprine and followed for 3 months. The incidence of pancreatitis was compared with unscreened historical controls. RESULTS: HLADQA1-HLADRB1*07:01A>C screening resulted in an 11-fold reduction in the incidence of azathioprine-induced pancreatitis (n = 1/328 or 0.30% vs n = 13/373 or 3.4%). In propensity score-matched cohorts (age and sex), HLA DQA1-HLADRB1*07:01A>C screening was significantly associated with a reduction in the incidence of AZA-induced pancreatitis independent of weight, glucocorticoid exposure, and smoking status (adjusted odds ratio = 0.075, 95% confidence interval = 0.01-0.58, P = 0.01). Up to 45% (n = 271/599) of participants were excluded from azathioprine therapy based on the haplotype in the HLADQA1-HLADRB1*07:01A>C-screened cohort. DISCUSSION: HLADQA1-HLADRB1*07:01A>C screening reduced the risk of azathioprine-induced pancreatitis; however, using this strategy to guide the use of azathioprine therapy in IBD may eliminate a large proportion of patients from being eligible for treatment with azathioprine. In regions where there is access to other IBD therapies, and given the short-term and long-term toxicities associated with azathioprine, HLADQA1-HLADRB1*07:01A>C-screening may be a clinically relevant strategy for enhancing the safe use of azathioprine in IBD. In addition, cost-effectiveness analyses are needed to further solidify the utility of HLADQA1-HLADRB1*07:01A>C screening in IBD populations.

Safety of Combination Biologic and Antirejection Therapy Post-Liver Transplantation in Patients With Inflammatory Bowel Disease.

BACKGROUND: Patients with inflammatory bowel disease (IBD) post-liver transplant (LT) may have bowel inflammation requiring biologic therapy. We aimed to evaluate the safety of combination biologic and antirejection therapy in IBD patients after LT from a tertiary center case series and an updated literature review. METHODS: Inflammatory bowel disease patients undergoing LT between 1985 and 2018 and requiring combination biologic and antirejection therapy post-LT were identified from the London Health Sciences Transplant Registry (Ontario, Canada). Safety outcomes were extracted by medical chart review. For an updated literature review, EMBASE, Medline, and CENTRAL were searched to identify studies evaluating the safety of combination biologic and antirejection therapy in IBD patients. RESULTS: In the case series, 19 patients were identified. Most underwent LT for primary sclerosing cholangitis (PSC; 14/19, 74%) treated with anti-integrins (8/19, 42%) or tumor necrosis factor α (TNF) antagonists (6/19, 32%). Infections occurred in 11/19 (58%) patients, most commonly Clostridium difficile (4/19, 21%). Two patients required colectomy, and 1 patient required re-transplantation. In the literature review, 13 case series and 8 case reports reporting outcomes for 122 IBD patients treated with biologic and antirejection therapy post-LT were included. PSC was the indication for LT in 97/122 (80%) patients, and 91/122 (75%) patients were treated with TNF antagonists. Infections occurred in 32/122 (26%) patients, primarily Clostridium difficile (7/122, 6%). CONCLUSIONS: Inflammatory bowel disease patients receiving combination biologic and antirejection therapy post-LT appeared to be at increased risk of Clostridium difficile. Compared with the general liver transplant population in the published literature, there was no increased risk of serious infection.

Crohn's Disease Is Associated with Decreased CYP3A4 and P-Glycoprotein Protein Expression.

Cytochrome P450 (CYP) 3A4 and P-glycoprotein (P-gp) have broad substrate overlap and are involved in the metabolism and transport of nearly 50% of currently prescribed medications. In the intestine, CYP3A4 and P-gp are coexpressed in the enterocytes at the intestinal villous tip and act in a coordinated manner to limit drug and xenobiotic oral bioavailability prior to further metabolism and disposition in the liver. Crohn's disease (CD), a form of inflammatory bowel disease, introduces a transmural intestinal insult that disrupts the intestinal barrier function; it therefore has the potential to affect intestinal drug metabolism and transport. We hypothesized that individuals with CD have reduced intestinal expression of CYP3A4 and P-gp. We obtained intestinal biopsy samples from individuals with and without CD and quantified the expression of CYP3A4 and P-gp. When we carried out Western analysis for protein expression, we observed a significant reduction in ileal (45% decrease) and colonic (78% decrease) CYP3A4 protein expression in subjects with CD compared with those without. Similarly, an 85% reduction in colonic P-gp protein expression was seen in the CD patients. Our data highlight important and novel findings pertaining to CD-associated changes to the intestinal expression of CYP3A4 and P-gp that are of relevance to better predict substrate drug dosing for patients with CD.

The utility of fecal calprotectin in predicting the need for escalation of therapy in inflammatory bowel disease.

BACKGROUND AND AIMS: Fecal calprotectin is an important biomarker used in the evaluation of inflammatory bowel disease. It has proven to be an effective tool in initial screening as well monitoring response to therapy. The aim of this study is to examine the utility of fecal calprotectin both as a predictor for the escalation of therapy in established inflammatory bowel disease and as a predictor of de novo diagnosis. METHODS: Patients with signs and symptoms concerning for inflammatory bowel disease presenting to outpatient clinics were recruited to provide fecal calprotectin stool samples prior to endoscopic evaluation. Patients were followed up for at least one year and monitored clinically for any change in symptomatology, escalation of therapy or development of IBD, confirmed endoscopically. RESULTS: A total of 126 patients, of whom 72 were known to have underlying inflammatory bowel disease, were included in the final analysis. Among the patients with elevated fecal calprotectin levels and known inflammatory bowel disease, 66% (33/50) went on to have escalation of therapy within 12 months compared to 18% (4/22) if the fecal calprotectin levels were in the normal range (p < .0001). For the remaining patients who at baseline did not have inflammatory bowel disease and a normal endoscopic evaluation, elevated fecal calprotectin resulted in no cases (0/17) of a new diagnosis in the next 12 months. CONCLUSIONS: Fecal calprotectin is a useful test for predicting escalation of therapy in established inflammatory bowel disease.

Self-Screening for Malnutrition Risk in Outpatient Inflammatory Bowel Disease Patients Using the Malnutrition Universal Screening Tool (MUST).

BACKGROUND AND AIMS: Malnutrition is common in patients with inflammatory bowel disease (IBD) and is associated with poor outcomes. Our aim is to determine if patient self-administered malnutrition screening using the malnutrition universal screening tool (MUST) is reliable by comparing patient scores with those derived from the healthcare practitioner (HCP), the gold standard. METHODS: We conducted a prospective validation study at a tertiary Canadian academic center that included 154 adult outpatients with IBD. All patients with IBD completed a self-administered nutrition screening assessment using the MUST score followed by an independent MUST assessment performed by HCPs. The main outcome measure was chance-corrected agreement (κ) of malnutrition risk categorization. RESULTS: For patient-administered MUST, the chance-corrected agreement κ (95% confidence interval [CI]) was 0.83 (0.74-0.92) when comparing low-risk and combined medium- and high-risk patients with HCP screening. Weighted κ analysis comparing all 3 risks groups yielded a κ (95% CI) of 0.85 (0.77-0.93) between patient and HCP screening. All patients were able to screen themselves. Overall, 96% of patients reported the MUST questionnaire as either very easy or easy to understand and to complete. CONCLUSION: Self-administered nutrition screening in outpatients with IBD is valid using the MUST screening tool and is easy to use. If adopted, this tool will increase utilization of malnutrition screening in hectic outpatient clinic settings and will help HCPs determine which patients require additional nutrition support.

Rapid fecal calprotectin testing to assess for endoscopic disease activity in inflammatory bowel disease: A diagnostic cohort study.

BACKGROUND AND AIM: With increasing numbers of patients diagnosed with inflammatory bowel disease (IBD), it is important to identify noninvasive methods of detecting disease activity. The aim of this study is to examine the diagnostic accuracy of fecal rapid calprotectin (FC) testing in the detection of endoscopically active IBD. PATIENTS AND METHODS: All consecutive patients presenting to outpatient clinics with lower gastrointestinal symptoms were prospectively recruited. Patients provided FC samples. Sensitivity (Sn), specificity (Sp), positive predictive value (PPV), and negative predictive value (NPV) for FC were calculated. Receiver-operator characteristics (ROC) curve was used to identify the ideal FC cutoff that predicts endoscopic disease activity. Correlation between FC and endoscopic disease activity, disease location, and C-reactive protein (CRP) levels were measured. RESULTS: One hundred and twenty-six patients, of whom 52% were females, were included in the final analysis with a mean age of 44.4 ± 16.7 years. Comparing FC to endoscopic findings, the following results were calculated: A cutoff point of 100 µg/g showed Sn = 83%, Sp = 67%, PPV = 65%, and NPV = 85%; and 200 µg/g showed Sn = 66%, Sp = 82%, PPV = 73%, and NPV = 77%. Based on ROC curve, the best FC cutoff point to predict endoscopic disease activity was 140 µg/g. Using this reference, FC levels strongly correlated with colorectal, ileocolonic, and ileal disease and predicted endoscopic activity. CONCLUSIONS: FC is an accurate test when used as an initial screening tool for patients suspected of having active IBD. Given its noninvasive nature, it may prove to reduce the need for colonoscopy and be an added tool in the management of IBD.

Methotrexate in combination with infliximab is no more effective than infliximab alone in patients with Crohn's disease.

BACKGROUND & AIMS: Methotrexate and infliximab are effective therapies for Crohn's disease (CD). In the combination of maintenance methotrexate-infliximab trial, we evaluated the potential superiority of combination therapy over infliximab alone. METHODS: In a 50-week, double-blind, placebo-controlled trial, we compared methotrexate and infliximab with infliximab alone in 126 patients with CD who had initiated prednisone induction therapy (15-40 mg/day) within the preceding 6 weeks. Patients were assigned randomly to groups given methotrexate at an initial weekly dose of 10 mg, escalating to 25 mg/week (n = 63), or placebo (n = 63). Both groups received infliximab (5 mg/kg of body weight) at weeks 1, 3, 7, and 14, and every 8 weeks thereafter. Prednisone was tapered, beginning at week 1, and discontinued no later than week 14. The primary outcome was time to treatment failure, defined as a lack of prednisone-free remission (CD Activity Index, <150) at week 14 or failure to maintain remission through week 50. RESULTS: Patients' baseline characteristics were similar between groups. By week 50, the actuarial rate of treatment failure was 30.6% in the combination therapy group compared with 29.8% in the infliximab monotherapy group (P = .63; hazard ratio, 1.16; 95% confidence interval, 0.62-2.17). Prespecified subgroup analyses failed to show a benefit in patients with short disease duration or an increased level of C-reactive protein. No clinically meaningful differences were observed in secondary outcomes. Combination therapy was well tolerated. CONCLUSIONS: The combination of infliximab and methotrexate, although safe, was no more effective than infliximab alone in patients with CD receiving treatment with prednisone. ClincialTrials.gov number, NCT00132899.

The safety and efficacy of adalimumab in patients with Crohn's disease: the experience of a single Canadian tertiary care centre.

BACKGROUND. Adalimumab (ADA), an antitumor necrosis factor (anti-TNF) monoclonal antibody, is effective in treating moderate-to-severely active Crohn's disease (CD). ADA has been associated with a variety of adverse events (AE). The purpose of this study is to determine the safety and efficacy of ADA in CD patients in clinical practice. METHODS. A retrospective analysis was performed on CD patients treated with ADA. Data extracted and analyzed included patient and CD demographics, remission and response rates with ADA, and safety and tolerability of ADA. RESULTS. A total of 149 ADA-treated CD patients were included. The mean duration of therapy with ADA was 20 months with 32% of patients discontinuing treatment. Anti-TNF-naïve and anti-TNF-exposed patients on ADA achieved clinical remission in 45% and 32%, had a clinical response in 23% and 23%, and had no clinical response in 32% and 45%, respectively. Anti-TNF-naïve and anti-TNF-exposed patients maintained remission in 82% and 67%, respectively. Fistulas healed in 19% and improved in 19%. AE occurred in 38% of patients with infection being the most common (20%). Serious infections lead to death in one (<1%). Logistic regression of AE did not identify statistically significant predictors except for colonic disease location (odds ratio [OR] = 0.31, 95% CI = 0.12-0.82, p = 0.018) and the rate of ADA discontinuation (OR = 3.24, 95% CI = 1.58-6.64, p = 0.0013). CONCLUSION. ADA is an effective treatment for CD. AE can occur commonly leading to discontinuation of medication and may be influenced by disease location. Although serious complications are rare, close monitoring of all patients on ADA is needed.

Transcutaneous bowel sonography for inflammatory bowel disease is sensitive and specific when performed in a nonexpert low-volume North American center.

OBJECTIVES: Transcutaneous bowel sonography is a nonionizing imaging modality used in inflammatory bowel disease. Although available in Europe, its uptake in North America has been limited. Since the accuracy of bowel sonography is highly operator dependent, low-volume centers in North America may not achieve the same diagnostic accuracy reported in the European literature. Our objective was to determine the diagnostic accuracy of bowel sonography in a nonexpert low-volume center. METHODS: All cases of bowel sonography at a single tertiary care center during an 18-month period were reviewed. Bowel sonography was compared with reference standards, including small-bowel follow-through, computed tomography, magnetic resonance imaging, colonoscopy, and surgical findings. RESULTS: A total of 103 cases were included for analysis during the study period. The final diagnoses included Crohn disease (72), ulcerative colitis (8), hemolytic uremic syndrome (1), and normal (22). The sensitivity and specificity of bowel sonography for intestinal wall inflammation were 87.8% and 92.6%, respectively. In the subset of patients who had complications of Crohn disease, the sensitivity and specificity were 50% and 100% for fistulas and 14% and 100% for strictures. One patient had an abscess, which was detected by bowel sonography. Abnormal bowel sonographic findings contributed to the escalation of treatment in 55% of cases. CONCLUSIONS: Bowel sonography for inflammatory bowel disease can be performed in low-volume centers and provides diagnostic accuracy for luminal disease comparable with published data, although it is less sensitive for complications of Crohn disease.

Predictors of disease severity in ulcerative colitis patients from Southwestern Ontario.

AIM: To understand the demographic characteristics of patients in Southwestern Ontario, Canada with ulcerative colitis (UC) in order to predict disease severity. METHODS: Records from 1996 to 2001 were examined to create a database of UC patients seen in the London Health Sciences Centre South Street Hospital Inflammatory Bowel Disease Clinic. To be included, patients' charts were required to have information of their disease presentation and a minimum of 5 years of follow-up. Charts were reviewed using standardized data collection forms. Disease severity was generated during the chart review process, and non-endoscopic Mayo Score criteria were collected into a composite. RESULTS: One hundred and two consecutive patients' data were entered into the database. Demographic analyses revealed that 51% of the patients were male, the mean age at diagnosis was 39 years, 13.7% had a first degree relative with inflammatory bowel disease (IBD), 61.8% were nonsmokers and 24.5% were ex-smokers. In 22.5% of patients the disease was limited to the rectum, in 21.6% disease was limited to the sigmoid colon, in 22.5% disease was limited to the left colon, and 32.4% of patients had pancolitis. Standard multiple regression analysis which regressed a composite of physician global assessment of disease severity, average number of bowel movements, and average amount of blood in bowel movements on year of diagnosis and age at time of diagnosis was significant, R(2) = 0.306, F (7, 74) = 4.66, P < 0.01. Delay from symptoms to diagnosis of UC, gender, family history of IBD, smoking status and disease severity at the time of diagnosis did not significantly predict the composite measure. CONCLUSION: UC severity is associated with younger age at diagnosis and year of diagnosis in a longitudinal cohort of UC patients, and may identify prognostic UC indicators.

Omega-3 free fatty acids for the maintenance of remission in Crohn disease: the EPIC Randomized Controlled Trials.

CONTEXT: Maintenance therapy for Crohn disease features the use of immunosuppressive drugs, which are associated with an increased risk of infection. Identification of safe and effective maintenance strategies is a priority. OBJECTIVE: To determine whether the oral administration of omega-3 free fatty acids is more effective than placebo for prevention of relapse of Crohn disease. DESIGN, SETTING, AND PATIENTS: Two randomized, double-blind, placebo-controlled studies (Epanova Program in Crohn's Study 1 [EPIC-1] and EPIC-2) conducted between January 2003 and February 2007 at 98 centers in Canada, Europe, Israel, and the United States. Data from 363 and 375 patients with quiescent Crohn disease were evaluated in EPIC-1 and EPIC-2, respectively. INTERVENTIONS: Patients with a Crohn's Disease Activity Index (CDAI) score of less than 150 were randomly assigned to receive either 4 g/d of omega-3 free fatty acids or placebo for up to 58 weeks. No other treatments for Crohn disease were permitted. MAIN OUTCOME MEASURE: Clinical relapse, as defined by a CDAI score of 150 points or greater and an increase of more than 70 points from the baseline value, or initiation of treatment for active Crohn disease. RESULTS: For EPIC-1, 188 patients were assigned to receive omega-3 free fatty acids and 186 patients to receive placebo. Corresponding numbers for EPIC-2 were 189 and 190 patients, respectively. The rate of relapse at 1 year in EPIC-1 was 31.6% in patients who received omega-3 free fatty acids and 35.7% in those who received placebo (hazard ratio, 0.82; 95% confidence interval, 0.51-1.19; P = .30). Corresponding values for EPIC-2 were 47.8% and 48.8% (hazard ratio, 0.90; 95% confidence interval, 0.67-1.21; P = .48). Serious adverse events were uncommon and mostly related to Crohn disease. CONCLUSION: In these trials, treatment with omega-3 free fatty acids was not effective for the prevention of relapse in Crohn disease. TRIAL REGISTRATION: clinicaltrials.gov Identifiers: EPIC-1: NCT00613197, EPIC-2: NCT00074542.

A survey of Canadian gastroenterologists about the use of methotrexate in patients with Crohn's disease.

BACKGROUND: Methotrexate (MTX) is effective in remission induction and maintenance in steroid-dependent Crohn's disease (CD), but is often considered to be a second-line immunosuppressive agent, to be used in cases of failure or intolerance to azathioprine (AZA) or 6-mercaptopurine (6-MP). This may be related to concerns about hepatotoxicity, but this adverse effect is rare in monitored CD patients taking MTX. Still, there are no guidelines for monitoring patients with CD on MTX, and physicians must decide based on rheumatological literature about how to monitor their patients. PURPOSE: To determine the patterns of MTX use in patients with CD by Canadian gastroenterologists, examining the reasons for choosing MTX versus AZA/6-MP, the doses and routes of administration of MTX, and how patients on MTX are monitored, including the use of liver biopsy. METHODS: A self-report survey was sent to physician members of the Canadian Association of Gastroenterology, with a second mailing three months later to increase response rate. RESULTS: Of 490 surveys mailed, a 54.9% response rate was achieved. Of adult gastroenterologists, 60.7% stated they never use MTX as a first-line immunosuppressive agent, and 33.3% never use MTX at all. The most common reasons for choosing MTX were a contraindication to the use of AZA/6-MP (43.7%) and patient preference (22.5%). MTX is used intramuscularly in 41.5%, subcutaneously in 31.8%, and orally in 26.7% of patients. The most common dose used for remission induction was 25 mg/week (84.2%; range 7.5 mg/week to 50 mg/week; three responders used more frequent dosing than weekly) and for remission maintenance was 15 mg/week (55.4%; range 7.5 mg/week to 50 mg/week; three responders used more frequent dosing than weekly). Most responders checked a liver profile and complete blood count at baseline and serially. Of those who used MTX, 26.5% routinely performed liver biopsy after an accumulated dose of MTX had been taken (usually 1 g to 2 g), 57.7% sometimes performed liver biopsy, and 16.8% never performed liver biopsy. Of pediatric gastroenterologists, 17.6% never used MTX, but those who used it prescribed it subcutaneously (80.0%) more often than intramuscularly (17.5%) or orally (2.5%). CONCLUSIONS: MTX was used as a first-line immunosuppressive agent in patients with CD by a minority of Canadian gastroenterologists. When used, there is variability in how MTX is prescribed and monitored. Although hepatotoxicity is rare, liver biopsy was performed frequently and probably often unnecessarily.