Romain Altwegg

Efficacy of adalimumab in patients with Crohn's disease and symptomatic small bowel stricture: a multicentre, prospective, observational cohort (CREOLE) study

Objective The efficacy of anti-tumour necrosis factors (anti-TNFs) in patients with Crohns disease (CD) and symptomatic small bowel stricture (SSBS) is controversial. The aim of this study was to estimate the efficacy of adalimumab in these patients and to identify the factors predicting success. Design We performed a multicentre, prospective, observational cohort study in patients with CD and SSBS. The included patients underwent magnetic resonance enterography at baseline and subsequently received adalimumab. The primary endpoint was success at week 24, defined as adalimumab continuation without prohibited treatment (corticosteroids after the eight week following inclusion, other anti-TNFs), endoscopic dilation or bowel resection. The baseline factors independently associated with success were identified using a logistic regression model, leading to a simple prognostic score. Secondary endpoints were prolonged success after week 24 (still on adalimumab, without dilation nor surgery) and time to bowel resection in the whole cohort. Results From January 2010 to December 2011, 105 patients were screened and 97 were included. At week 24, 62/97 (64%) patients had achieved success. The prognostic score defined a good prognosis group with 43/49 successes, an intermediate prognosis group with 17/28 successes and a poor prognosis group with 1/16 successes. After a median follow-up time of 3.8 years, 45.7%±6.6% (proportion±SE) of patients who were in success at week 24 (ie, 29% of the whole cohort) were still in prolonged success at 4 years. Among the whole cohort, 50.7%±5.3% of patients did not undergo bowel resection 4 years after inclusion. Conclusions A successful response to adalimumab was observed in about two-thirds of CD patients with SSBS and was prolonged in nearly half of them till the end of follow-up. More than half of the patients were free of surgery 4 years after treatment initiation. Clinical Trial registration number NCT01183403; Results.

One-year effectiveness and safety of vedolizumab therapy for inflammatory bowel disease: a prospective multicentre cohort study

We recently showed that vedolizumab is effective in patients with Crohns disease (CD) and ulcerative colitis (UC) with prior anti‐TNF failure in a multicentre compassionate early‐access programme before marketing authorisation was granted to vedolizumab.

Negative Screening Does Not Rule Out the Risk of Tuberculosis in Patients with Inflammatory Bowel Disease Undergoing Anti-TNF Treatment: A Descriptive Study on the GETAID Cohort

AIM to describe the characteristics of incident cases of tuberculosis [TB] despite negative TB screening tests, in patients with inflammatory bowel disease [IBD] undergoing anti-TNF treatment, and to identify the risk factors involved. METHODS A retrospective descriptive study was conducted at GETAID centers on all IBD patients undergoing anti-TNF treatment who developed TB even though their initial screening test results were negative. The following data were collected using a standardized anonymous questionnaire: IBD, and TB characteristics and evolution, initial screening methods and results, and time before anti-TNF treatment was restarted. RESULTS A total of 44 IBD patients [including 23 men; median age 37 years] were identified at 20 French and Swiss centers at which TB screening was performed [before starting anti-TNF treatment] based on Tuberculin Skin Tests [n = 25], Interferon Gamma Release Assays [n = 12], or both [n = 7]. The median interval from the start of anti-TNF treatment to TB diagnosis was 14.5 months (interquartile range [IQR] 25-75: 4.9-43.3). Pulmonary TB involvement was observed in 25 [57%] patients, and 40 [91%] had at least one extrapulmonary location. One TB patient died as the result of cardiac tamponade. Mycobacterium tuberculosis exposure was thought to be a possible cause of TB in 14 cases [32%]: 7 patients [including 6 health care workers] were exposed to occupational risks, and 7 had travelled to endemic countries. Biotherapy was restarted on 27 patients after a median period of 11.2 months [IQR 25-75: 4.4-15.2] after TB diagnosis without any recurrence of the infection. CONCLUSION Tuberculosis can occur in IBD patients undergoing anti-TNF treatment, even if their initial screening results were negative. In the present population, TB was mostly extrapulmonary and disseminated. TB screening tests should be repeated on people exposed to occupational risks and/or travelers to endemic countries. Restarting anti-TNF treatment seems to be safe.

Impact of vedolizumab therapy on extra‐intestinal manifestations in patients with inflammatory bowel disease: a multicentre cohort study nested in the OBSERV‐IBD cohort

The effectiveness of vedolizumab as a treatment for extraintestinal manifestations (EIM) is questionable due to its gut‐specificity.

Inflammatory bowel diseases in anti-neutrophil cytoplasmic antibody–associated vasculitides: 11 retrospective cases from the French Vasculitis Study Group

OBJECTIVE Coexistence of ANCA-associated vasculitis (AAV) and IBD is a rare condition that is rarely described in the literature. The aim of the study was to describe the main characteristics of patients presenting with both IBD and AAV. METHODS A retrospective study of AAV patients in the French Vasculitis Study Group cohort who also had a diagnosis of IBD was conducted. We reviewed the medical records and outcomes of these patients. RESULTS We identified 11 patients with AAV and IBD. Four patients with eosinophilic granulomatosis with polyangiitis (Churg-Strauss) also had ulcerative colitis and seven patients with granulomatosis with polyangiitis (GPA) had Crohns disease. No Crohns disease was observed in eosinophilic GPA and no ulcerative colitis in GPA. IBD started before AAV manifestations in six cases, simultaneously in two cases and after AAV manifestations in three cases. CONCLUSION Coexistence of IBD and AAV is a rare condition. The therapeutic management of these patients includes corticosteroids in all cases and immunosuppressive drugs in some patients. Coexistence of IBD and AAV might be explained by common underlying inflammatory responses and cytokine profiles polarized towards either Th1 or Th2. Finally, in the presence of digestive manifestations in the context of AAV, the hypothesis of IBD should be assessed.

Management of Ulcerative Colitis Using Vedolizumab After Liver Transplantation for Primary Sclerosing Cholangitis

The therapeutic approaches for treating inflammatory bowel disease [IBD] after liver transplantation [LT] are greatly debated. There are some studies about the effectiveness of using corticosteroids, 5-aminosalicylates [5ASA], and immunomodulators, such as azathioprine, methotrexate, or cyclosporine, but there is still little experience in using biological therapies to treat liver transplant recipients.1 To date, in the literature there have only been 28 patients treated with anti-tumour necrosis factor [TNF] for IBD relapse following LT; this number includes patients with ulcerative colitis [UC], Crohn’s disease, indeterminate colitis, and pouchitis treated effectively with infliximab or adalimumab.2 …

Efficacy and safety of golimumab in Crohn's disease: a French national retrospective study

Anti‐tumour necrosis factor (TNF) agents have improved the care of Crohns disease (CD). After the first anti‐TNF discontinuation, it is possible to switch to another anti‐TNF. Three anti‐TNF agents are available for ulcerative colitis (infliximab, adalimumab and golimumab), but only the first 2 have been approved for CD because golimumab has not been studied for this indication.

Outcomes 7 Years After Infliximab Withdrawal for Patients With Crohn’s Disease in Sustained Remission

BACKGROUND & AIMS: Little is known about long‐term outcomes of patients with Crohn’s disease (CD) after infliximab withdrawal. We aimed to describe the long‐term outcomes of patients with CD in clinical remission after infliximab treatment was withdrawn. METHODS: We performed a retrospective analysis of data from the 115 patients included in the infliximab discontinuation in patients with CD in stable remission on combined therapy with antimetabolites (STORI) study, performed at 20 centers in France and Belgium from March 2006 through December 2009. The STORI cohort was a prospective analysis of risk and factors associated with relapse following withdrawal of maintenance therapy with infliximab, maintained on antimetabolites, while in clinical remission. We collected data from the end of the study until the last available follow‐up examination on patient surgeries, new complex perianal lesions (indicating major complications), and need for and outcomes of restarting therapy with infliximab or another biologic agent. The de‐escalation strategy was considered to have failed when a major complication or infliximab restart failure occurred. RESULTS: Of the 115 patients initially included, data from 102 patients (from 19 of the 20 study centers) were included in the final analysis. The median follow‐up time was 7 years. Twenty‐one percent of the patients did not restart treatment with infliximab or another biologic agent and did not have a major complication 7 years after infliximab withdrawal (95% CI, 13.1–30.3). Among patients who restarted infliximab, treatment failed for 30.1% 6 years after restarting (95% CI, 18.5–42.5). Overall, at 7 years after stopping infliximab therapy, major complications occurred in 18.5% of patients (95% CI, 10.2–26.8) whereas 70.2% of patients had no failure of the de‐escalation strategy (95% CI, 60.2–80.1). Factors independently associated with major complications were upper‐gastrointestinal location of disease, white blood cell count ≥ 5.0 × 109/L, and hemoglobin level ≤12.5 g/dL at the time of infliximab withdrawal. Patients with at least 2 of these factors had a more than 40% risk of major complication in the 7 years following infliximab withdrawal. CONCLUSIONS: In a long‐term follow‐up of the STORI cohort (7 years) one fifth of the patients did not restart infliximab or another biologic agent and did not develop major complications. Seventy percent of patients had no failure of the de‐escalation strategy (no major complication and no failure of infliximab restart).

DOP071 Inflammatory bowel diseases: a new cardiovascular risk factor?

DOP071 Inflammatory bowel diseases: a new cardiovascular risk factor? L. Caillo1 *, G. Danan1, V. Georgescu2, L. Papineau1, F. Gonzalez1, J.-F. Bourgaux3, F. Guillon4, G.-P. Pageaux1, R. Altwegg1 *. 1University Hospital of St Eloi, Departement of Hepatology and Gastroenterology, Montpellier, France, 2University Hospital, Department of Medical Information, Montpellier, France, 3University Hospital, Department of Hepatology and Gastroenterology, Nimes, France, 4University Hospital of St Eloi, Department of Digestive Surgery, Montpellier, France

Effectiveness and safety of anti-TNF therapy for inflammatory bowel disease in liver transplant recipients for primary sclerosing cholangitis: A nationwide case series

BACKGROUND There is a lack of consensus regarding the treatment of inflammatory bowel disease (IBD) after liver transplantation (LT) forprimary sclerosing cholangitis (PSC). AIM To investigate the safety and effectiveness of anti-TNF therapy in patients with IBD after a LT for PSC. METHODS We reviewed the medical files of all of the IBD patients who underwent a LT for PSC and who were treated with anti-TNF therapy at 23 French liver transplantation centers between 1989 and 2012. RESULTS Eighteen patients (12 with ulcerative colitis and 6 who had Crohns disease) were recruited at 9 LT centers. All of these patients received infliximab or adalimumab following their LT, and the median duration of their anti-TNF treatment was 10.4 months. The most frequent concomitant immunosuppressive treatment comprised a combination of tacrolimus and corticosteroids. Following anti-TNF therapy induction, a clinical response was seen in 16/18 patients (89%) and clinical remission in 10 (56%). At the end of the anti-TNF treatment or at the last follow-up examination (the median follow-up was 20.9 months), a clinical response was achieved in 12 patients (67%) and clinical remission in 7 (39%). A significant endoscopic improvement was observed in 9 out of 14 patients and a complete mucosal healing in 3 out of 14 patients (21%). Six patients experienced a severe infection. These were due to cholangitis, cytomegalovirus (CMV) infection, Clostridium difficile, cryptosporidiosis, or Enterococcus faecalis. Three patients developed colorectal cancer after LT, and two patients died during the follow-up period. CONCLUSIONS Anti-TNF therapy proved to be effective for treating IBD after LT for PSC. However, as 17% of the patients developed colorectal cancer during the follow-up, colonoscopic annual surveillance is recommended after LT, as specified in the current guidelines.