Anti-tumour necrosis factor discontinuation in inflammatory bowel disease patients in remission: study protocol of a prospective, multicentre, randomized clinical trial

Background: Patients with inflammatory bowel disease who achieve remission with anti-tumour necrosis factor (anti-TNF) drugs may have treatment withdrawn due to safety concerns and cost considerations, but there is a lack of prospective, controlled data investigating this strategy. The primary study aim is to compare the rates of clinical remission at 1?year in patients who discontinue anti-TNF treatment versus those who continue treatment. Methods: This is an ongoing, prospective, double-blind, multicentre, randomized, placebo-controlled study in patients with Crohn?s disease or ulcerative colitis who have achieved clinical remission for ?6?months with an anti-TNF treatment and an immunosuppressant. Patients are being randomized 1:1 to discontinue anti-TNF therapy or continue therapy. Randomization stratifies patients by the type of inflammatory bowel disease and drug (infliximab versus adalimumab) at study inclusion. The primary endpoint of the study is sustained clinical remission at 1?year. Other endpoints include endoscopic and radiological activity, patient-reported outcomes (quality of life, work productivity), safety and predictive factors for relapse. The required sample size is 194 patients. In addition to the main analysis (discontinuation versus continuation), subanalyses will include stratification by type of inflammatory bowel disease, phenotype and previous treatment. Biological samples will be obtained to identify factors predictive of relapse after treatment withdrawal. Results: Enrolment began in 2016, and the study is expected to end in 2020. Conclusions: This study will contribute prospective, controlled data on outcomes and predictors of relapse in patients with inflammatory bowel disease after withdrawal of anti-TNF agents following achievement of clinical remission. Clinical trial reference number: EudraCT 2015-001410-1

Efficacy, safety and cost-efficiency of adalimumab 80 mg every other week in previously intensified IBD patients under treatment with adalimumab 40 mg every week

Background Dose escalation is often recommended for loss of response in patients with inflammatory bowel disease (IBD) under maintenance treatment with anti-TNF, but in normal conditions this strategy considerably increases the cost. A new presentation of Adalimumab (ADA) 80 mg has been approved in our hospital with the same price per unit as the ADA 40 mg presentation. The aim of this study was to evaluate the efficacy, safety and cost-efficiency of ADA 80 mg every other week (eow) in IBD patients under previously intensified treatment with ADA 40 mg every week. Methods A prospective and observational study was performed. Inclusion criteria were all IBD patients under intensified maintenance therapy with ADA 40 mg every week. Physicians informed all patients the reasons (cost and convenience) for changing to a ADA 80 mg eow dose and asked for their consent. So far we have evaluated a period of 1 month, although the complete follow-up period will be 12 months. The Harvey?Bradshaw index (HBI ?4) and the Mayo partial index (Mayo partial index ?2) were used to evaluate clinical remission in Crohn?s disease (CD) and ulcerative colitis (UC) patients, respectively. Adverse events were monitored. Faecal calprotectin (FC) and C reactive protein (CRP) were collected at baseline (week 0, before first dose of subcutaneous injection of ADA 80 mg) and after 1 month. Biological remission was defined as clinical remission and FC < 250 ?g/g and CRP < 5 mg/dl. A descriptive analysis was performed and data are shown as percentage, median and range. Cost efficiency analysis was also performed. Results We offered to 18 consecutive IBD patients the possibility of participating in the study, but only 16 agreed to participate. We included 15 CD and 1 extensive UC with a median age of 40. 56.3% were male, 37.5% non-smokers and 31.3% ex-smokers. In CD, 46.7% had ileal disease, 13.3% colonic disease and 40% ileocolonic disease. 46.7% CD patients presented fistulising behaviour. At baseline, 86.7% of patients were in clinical remission and 92.3% were in clinical remission after 1 month. Median FC concentration at inclusion was 210 (range 6?1900) and 1 month later 91 (range 10?3754). Median CRP concentration at inclusion was 0.14 (range 0?19) and 0.21 (range 0.01?2.94) at month 1. 60% of patients at month 0 and 53.3% at month 1 were in biological remission. No adverse events were registered. After 1 month in total we had saved more than 13.000 euros and if all patients complete 1 year of treatment we predict savings of more than 150.000 euros with our new schedule of treatment. Conclusions Changing to a single dose ADA 80 mg eow is an efficacy, safety and cost-efficient strategy in IBD patients under intensified maintenance therapy with ADA 40 mg every week