BERLIN — Psoriasis patients randomized to adalimumab plus adjunctive topical therapy experienced significantly greater reduction in disease severity and greater quality-of-life improvements through the first 4 weeks of therapy than those on adalimumab plus vehicle in the BELIEVE trial.
Adding fixed-dose combination topical calcipotriol/betamethasone dipropionate ointment to adalimumab brought more rapid initial improvement, compared with adalimumab monotherapy, but the advantage was not sustained.
From week 8 through week 16, when the study concluded, most outcomes in the two treatment arms were no longer statistically different. And in the few end points where there was a significant difference at week 16, adalimumab monotherapy—not combination treatment—was the winner, Dr. Diamant Thaçi reported at the annual congress of the European Academy of Dermatology and Venereology.
BELIEVE was a phase IIIb randomized, double-blind clinical trial involving 730 European patients with moderate to severe psoriasis who had previously failed two or more classic nonbiologic systemic therapies. In addition, more than half of the subjects had a history of prior therapy with one or more anti–tumor necrosis factor (TNF) drugs, noted Dr. Thaçi of Johann Wolfgang Goethe University, Frankfurt.
All participants received an initial 80-mg subcutaneous dose of adalimumab (Humira), followed by a 40-mg dose every 2 weeks. In addition, they were randomized to topical calcipotriol/betamethasone (Taclonex, Dovobet, Daivobet) or placebo applied once daily during the first 4 weeks, then on an as-needed basis.
The primary study end point—a 75% improvement from baseline in Psoriasis Area and Severity Index (PASI-75) scores at week 16—was achieved by 64.8% of patients in the combination arm and a statistically similar 70.9% of those on adalimumab plus vehicle, Dr. Thaçi said.
This week-16 trend favoring monotherapy for PASI-75 achieved significance for PASI-90: a 50.3% rate with monotherapy, compared with 38.8% with combination therapy, he said. The week-16 PASI-100 rate of 24% with monotherapy also was significantly better than the 15% with combination therapy.
“I cannot explain the reason for this at the moment, but I hope in the near future we'll have more explanation about this after we finish ongoing subanalyses,” Dr. Thaçi said.
Of importance to long-suffering patients, however, clinical improvement came significantly more swiftly with the biologic/topical therapy combination. The PASI-75 rate at week 2 was 14.8% with combination therapy and 5.8% with adalimumab monotherapy. At week 4, the PASI-75 rate was 40.7% with combination therapy, compared with 32.4% with monotherapy.
Similarly, initial improvements in various patient-reported quality-of-life measures were significantly greater through week 4 with combination therapy. The implication is that combined biologic/topical therapy for the first month is advantageous but after that it has no benefit, he said.
From a mean baseline score of 14 on the 30-point Dermatology Life Quality Index (DLQI), at week 2 the combination therapy group showed a 47.5% improvement, significantly better than the 32.1% with adalimumab plus placebo. At week 4, the between-group difference remained significant: a mean 60.9% improvement on DLQI over baseline with combination therapy, compared with 46.6% with monotherapy. At week 16, patients on combination therapy had a mean 67.2% improvement, similar to the 71.5% with monotherapy, said Dr. Thaçi.
At week 2, patients in the combined therapy arm had a mean 60% reduction from baseline on visual analog pruritus scores, markedly better than the 37.5% decrease with monotherapy. The advantage in favor of combination therapy was maintained at week 4, with a 75% reduction in pruritus, as compared with 57.1% for monotherapy. By week 16, however, the reductions of 83.3% with combination therapy and 88.9% with monotherapy were statistically similar.
The same pattern was seen with regard to change over time in visual analog pain scores, he said.
The week-16 PASI-75 rate was 71.7% in anti-TNF-naive patients and nearly as good in patients with prior anti-TNF therapy, with a 65% PASI-75 in previous etanercept (Enbrel) users and a 59% rate in those with a history of infliximab (Remicade) use, Dr. Thaçi noted.
BELIEVE was sponsored by Abbott (manufacturer of Humira), and the topical calcipotriol/betamethasone was provided by LEO Pharma. Dr. Thaci is a consultant to Abbott.
Clinical improvement came significantly more swiftly with the biologic/topical therapy combination.
Source DR. THAÇI