Phase 3 trial indicates adalimumab efficacy, safety

May 1, 2007

A North American phase 3, double-blind trial randomized 1,212 patients with moderate-to-severe psoriasis 2:1 to subcutaneous adalimumab (80 mg initially, then 40 mg every other week) or placebo. Adalimumab resulted in rapid improvement in psoriasis, and after 16 weeks, 71 percent of adalimumab-treated patients, compared with only 6.5 percent of controls, achieved a 75 percent improvement in PASI score. Sustained efficacy was observed in patients who were treated to 33 weeks and in ~95 percent of patients who continued on adalimumab to week 52. No significant safety issues were observed.

Key Points

Washington - Analyses of data from a North American phase 3 clinical trial confirm the safety and significant efficacy of subcutaneous adalimumab (Humira, Abbott) for the treatment of moderate-to-severe chronic plaque psoriasis, Alan Menter, M.D., says.

Safety was also favorable. In the phase 3 trial, there were no differences in rates of serious adverse events, serious infectious adverse events, or malignancies between adalimumab and placebo-treated patients during the first 16 weeks of treatment, nor did any significant safety concerns emerge during longer-term treatment.

"The safety outcomes in the phase 3 study were also reassuring in terms of the rate of malignancy, tuberculosis, and other adverse events that are potential concerns with anti-TNF therapy, but not a surprise, as they are consistent with the record established for adalimumab in 180,000-plus treated patients over nine years of use," Dr. Menter says.

Participants were initially randomized to receive adalimumab (80 mg at week zero and then 40 mg every other week beginning at week one) or placebo for 16 weeks. The proportion of patients achieving a 75 percent improvement in PASI score at week 16 was analyzed as one of the study's two primary endpoints and showed a significant difference favoring adalimumab versus placebo (71 percent vs. 6.5 percent). A PASI-90 response (90 percent improvement from baseline PASI score) was achieved by 45 percent of adalimumab patients versus only 1.8 percent of the controls at week 16.

"These results are impressive, with adalimumab demonstrating superiority by the first efficacy assessment performed at week four. At that visit, adalimumab patients had a mean 52 percent improvement in their PASI score, and 19 percent had achieved a PASI-75 response compared with only 1.3 percent of placebo-treated patients," Dr. Menter says.

Patients in the adalimumab and placebo groups who achieved a PASI-75 response at week 16 continued on open-label treatment with adalimumab, 40 mg, every other week through week 33. Continuation of adalimumab through week 33 was associated with sustained response among patients who remained on adalimumab; the mean percentage improvement from baseline PASI was stable in 90 percent of patients at weeks 16, 24, and 33.