Review: Efficacy and safety of adalimumab in Crohn's disease

Abstract

Adalimumab (ADA) is a subcutaneously (SC) self-administered fully human Ig G1 monoclonal antibody directed against tumor necrosis factor alpha (TNF). In the CLASSIC I dose-ranging trial, ADA was superior to placebo for inducing remission in patients with moderate-to-severe Crohn's disease (CD) naive to TNF inhibitor therapy. In CLASSIC II, patients in remission following CLASSIC I maintained remission for up to 56 weeks while on ADA. In CHARM, approximately 40% of the 499 patients with moderate-to-severe CD who responded to ADA, maintained remission at 26 and 52 weeks, thus confirming long-term efficacy. ADA demonstrated steroid-sparing properties, beneficial effects in patients with perianal fistulas, and decreases in rates of hospitalization and surgery. Sub-group analyses demonstrated similar remission rates irrespective of concomitant immunosuppressive use or previous exposure to other TNF inhibitor therapy. In the GAIN trial, 325 patients who had either lost response or become intolerant to infliximab (IFX) were randomized to recieve ADA induction therapy or placebo. In this difficult-to-treat patient population, 21% achieved remission and half demonstrated clinical benefit from ADA induction therapy. Injection site reactions may occur with SC ADA (2-5% of patients), which are generally less dramatic in nature than infusion reactions experienced with intravenous IFX. Immunogenicity occurs with all monoclonal antibodies; however, in the CD development program anti-ADA antibodies were detected at low rates (0.7 and 2.6% of patients in the CLASSIC I and CLASSIC II studies, respectively). Based on robust short-and long-term efficacy data from large randomized controlled trials and a favorable safety signal, ADA has become a key addition to the therapeutic armamentarium in the treatment of moderate-to-severe CD.

Safety and Efficacy of Adalimumab for Patients With Moderate to Severe Crohn's Disease: The Taiwan Society of Inflammatory Bowel Disease (TSIBD) Study

“…The safety and efficacy of ADA for CD have been extensively tested in Western countries, but much less so in Asian countries 3,6,7,8,9,10,11. In Japan, ADA was approved for CD treatment since 2010.…”

Small Bowel Crohn's Disease: An Emerging Disease Phenotype?

“…However, with the emergence of immunosuppressants, such as azathioprine/6-mercaptopurine and biological agents, additional therapeutic options are now available. Biological therapies have been shown to be capable of inducing and maintaining remission in patients with active CD [81,82]. …”

Hair Loss in Patients with Inflammatory Bowel Disease

“…Both infliximab (IFX) and adalimumab (ADA) information sheets report hair loss to be a possible uncommon side effect (IFX: 1-10 patients per 1000 and ADA: unknown), although in the large trials of IFX and ADA in IBD, alopecia was not reported as a common side effect. [65][66][67][68] Twenty-five cases of hair loss in association with anti-TNF have been reported to date, the majority presenting with AA. Seven were being treated for IBD, 4 with IFX, 69-71 and 3 with ADA.…”