Objective The aim of this study was to assess the efficacy and safety of adalimumab (ADA), a recombinant human monoclonal antibody against tumour necrosis factor alpha (TNF), for the induction of... Show moreObjective The aim of this study was to assess the efficacy and safety of adalimumab (ADA), a recombinant human monoclonal antibody against tumour necrosis factor alpha (TNF), for the induction of clinical remission in anti-TNF naive patients with moderately to severely active ulcerative colitis. Methods This 8-week, multicentre, randomised, double-blind, placebo-controlled study (NCT00385736), conducted at 94 centres in North America and Europe, enrolled ambulatory adult patients with Mayo score of >= 6 points and endoscopic subscore of >= 2 points despite treatment with corticosteroids and/or immunosuppressants. Under the original study protocol, 186 patients were randomised (1: 1) to subcutaneous treatment with ADA160/80 (160 mg at week 0, 80 mg at week 2, 40 mg at weeks 4 and 6) or placebo. Subsequently, at the request of European regulatory authorities, the protocol was amended to include a second induction group (ADA80/40: 80 mg at week 0, 40 mg at weeks 2, 4 and 6). The primary efficacy endpoint was clinical remission (Mayo score <= 2 with no individual subscore > 1) at week 8, assessed in 390 patients randomised (1: 1: 1) to ADA160/80, ADA80/40, or placebo. Safety was assessed in all enrolled patients. Patients, study site personnel, investigators, and the sponsor were blinded to treatment assignment. Results At week 8, 18.5% of patients in the ADA160/80 group (p=0.031 vs placebo) and 10.0% in the ADA80/40 group (p=0.833 vs placebo) were in remission, compared with 9.2% in the placebo group. Serious adverse events occurred in 7.6%, 3.8% and 4.0% of patients in the placebo, ADA80/40, and ADA160/80 groups, respectively. There were two malignancies in the placebo group, none in the ADA groups. There were no cases of tuberculosis and no deaths. Conclusions ADA160/80 was safe and effective for induction of clinical remission in patients with moderately to severely active ulcerative colitis failing treatment with corticosteroids and/or immunosuppressants. Show less
D'Haens, G.R.; Panaccione, R.; Higgins, P.D.R.; Vermeire, S.; Gassull, M.; Chowers, Y.; ... ; Travis, S. 2011
The advent of biological therapy has revolutionized inflammatory bowel disease (IBD) care. Nonetheless, not all patients require biological therapy. Selection of patients depends on clinical... Show moreThe advent of biological therapy has revolutionized inflammatory bowel disease (IBD) care. Nonetheless, not all patients require biological therapy. Selection of patients depends on clinical characteristics, previous response to other medical therapy, and comorbid conditions. Availability, reimbursement guidelines, and patient preferences guide the choice of first-line biological therapy for luminal Crohn's disease (CD). Infliximab (IFX) has the most extensive clinical trial data, but other biological agents (adalimumab (ADA), certolizumab pegol (CZP), and natalizumab (NAT)) appear to have similar benefits in CD. Steroid-refractory, steroid-dependent, or complex fistulizing CD are indications for starting biological therapy, after surgical drainage of any sepsis. For fistulizing CD, the efficacy of IFX for inducing fistula closure is best documented. Unique risks of NAT account for its labeling as a second-line biological agent in some countries. Patients who respond to induction therapy benefit from systematic re-treatment. The combination of IFX with azathioprine is better than monotherapy for induction of remission and mucosal healing up to 1 year in patients who are naive to both agents. Whether this applies to other agents remains unknown. IFX is also effective for treatment-refractory, moderate, or severely active ulcerative colitis. Patients who have a diminished or loss of response to anti-tumor necrosis factor (TNF) therapy may respond to dose adjustment of the same agent or switching to another agent. Careful consideration should be given to the reasons for loss of response. There are insufficient data to make recommendations on when to stop anti-TNF therapy. Preliminary evidence suggests that a substantial proportion of patients in clinical remission for > 1 year, without signs of active inflammation can remain in remission after stopping treatment. Show less
