Adalimumab

Key Points

Humira Adalimumab ABBOTT Recombinant monoclonal antibody approved for reducing the signs and symptoms and inducing and maintaining clinical remission of moderately-to-severely active Crohn's disease

This recombinant human monoclonal antibody binds specifically to tumor necrosis factor (TNF)-alpha, a cytokine involved in normal inflammatory and immune responses. This binding blocks TNF-alpha's interaction with the p55 and p75 cell surface TNF receptors. Adalimumab was previously approved for the treatment of rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. On February 27, 2007, adalimumab was approved for reducing the signs and symptoms and inducing and maintaining clinical remission in adult patients with moderately-to-severely active Crohn's disease who have had an inadequate response to conventional therapy and for reducing the signs and symptoms and inducing clinical remission in these patients if they have also lost response to or are intolerant to infliximab.

Efficacy. The efficacy of adalimumab was assessed in adult patients with moderately-toseverely active Crohn's disease (Crohn's Disease Activity Index [CDAI] ≥220 and ≤450) in randomized, double-blind, placebocontrolled studies. In Studies CD-I and CD-II, induction of clinical remission (defined as CDAI <150) was assessed. In Study CD-I, 299TNF-blocker-naïve patients were randomized to 1 of 4 treatment groups: adalimumab 160 mg at Week 0 and 80 mg at Week 2, adalimumab 80 mg at Week 0 and 40 mg at Week 2, adalimumab 40 mg at Week 0 and 20 mg at Week 2, or placebo at Weeks 0 and 2. In Study CD-II, 325 patients who had lost response to or were intolerant to infliximab therapy were randomized to receive either adalimumab 160 mg at Week 0 and 80 mg at Week 2 or placebo at Weeks 0 and 2. Clinical results for both studies were evaluated at Week 4. In both trials, a greater percentage of patients treated with adalimumab 160 mg at Week 0 and 80 mg at Week 2 experienced induction of clinical remission versus those treated with placebo (CD-I: adalimumab 160/80 mg, 36%; placebo, 12%; P<.01; CD-II: adalimumab 160/80 mg, 21%; placebo, 7%; P<.01). Maintenance of clinical remission was evaluated in Study CD-III, which enrolled 854 patients with active disease. All patients received open-label adalimumab 80 mg at Week 0 and 40 mg at Week 2. Patients were randomized at Week 4 to receive adalimumab 40 mg either every week or every other week or placebo. Total study duration was 56 weeks. The results demonstrated that 58% of patients had experienced a clinical response (decrease inCDAI ≥70) at Week 4. At Weeks 26 and 56, a greater proportion of these clinical-response patients who were receiving adalimumab 40 mg every other week had achieved clinical remission versus clinical-response patients who had been randomized to placebo (Week 26: adalimumab 40 mg every other week, 40%; placebo, 17%; P<.001; Week 56: adalimumab 40 mg every other week, 36%; placebo, 12%; P<.001).

Dosing. The recommended adalimumab dose regimen for patients with Crohn's disease is 160 mg initially at Week 0 (administered as 4 injections in 1 day or as 2 injections per day for 2 consecutive days), 80 mg at Week 2, and a maintenance dose of 40 mg every other week beginning at Week 4.