Abbott Laboratories (ABBOTT PARK, Illinois) announced that it has received marketing authorization from the European Commission for the use of Humira® (adalimumab) as a treatment for severe Crohn's disease (CD). Humira is the first self-administered biologic for the treatment of CD. The announcement follows US FDA approval in February 2007 for the CD indication and is the fourth approved indication for Humira in the US and the EU.

The approval was based on data from three pivotal trials: CLASSIC I, CHARM, and GAIN. These trials supporting the drug's indication for CD, evaluated Humira in more than 1400 adult patients with moderate-to-severe, active CD, ranging from those who were naïve to anti-TNFα therapy to those who had previously lost response or who were unable to tolerate infliximab (Remicade®, Centocor Inc). In each trial, clinical remission was measured by the Crohn's Disease Activity Index (CDAI) of less than 150.

The CLASSIC I induction trial evaluated Humira for the induction of clinical remission in 299 anti-TNF naïve patients, of whom 36% and 24% receiving Humira (160 mg at week 0 followed by 80 mg at week 2, and 80 mg at week 0 followed by 40 mg at week 2, respectively) achieved clinical remission at week 4 compared to 12% treated with placebo (P<.001 for 160 mg/80 mg dose group and P = .06 for 80 mg/40 mg dose group).

The CHARM trial studied Humira for the maintenance of clinical remission. CHARM was a 56-week trial that enrolled 854 patients with moderate-to-severe CD. After a 4-week open-label induction phase during which all subjects received 80 mg Humira at week 0, followed by 40 mg Humira at week 2, 58% of patients (n = 499) demonstrated clinical response (a CDAI decrease >e;70 from baseline). These patients were randomized to receive 40 mg Humira either eow or weekly, or placebo. Of the patients who continued Humira 40 mg eow (n = 172), 40% were in clinical remission at week 26 (P<.001) and 36% were in remission at week 56 (P<.001), versus 17% and 12% in the placebo group, respectively. For those who continued taking Humira 40 mg weekly, 47% were in clinical remission at week 26 and 41% were in remission at week 56 (P<.001).

In GAIN, a 4-week induction trial of 325 patients who lost response or who were intolerant to infliximab, three times as many patients taking Humira achieved clinical remission at week 4 versus placebo (21% vs 7%).

In the EU, the recommended Humira induction dose for adult patients with severe CD is 80 mg at week 0, followed by 40 mg at week 2. Patients who require a more rapid response to therapy can take 160 mg at week 0 (dose can be administered as four injections in 1 day or as two injections per day for 2 consecutive days), followed by 80 mg at week 2, with the awareness that the risk for adverse events is higher during induction.

In addition to CD, Humira is approved in Europe and the US for the treatment of rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. To date, Humira has been approved in 67 countries and more than 180,000 people worldwide are being treated with Humira. Clinical trials are under way to evaluate the potential of Humira in other immune-mediated diseases.

—A. Techman

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