GLASGOW, SCOTLAND — In the first phase III trial evaluating infliximab for plaque psoriasis, substantial improvements were achieved by week 10 and sustained through week 50 in the majority of patients, Kristian Reich, M.D., reported at the annual meeting of the British Association of Dermatologists.
The 281 patients who were randomized to receive either placebo or infusions of infliximab, 5 mg/kg at week 0, 2, and 6 and every 8 weeks thereafter all had severe, recalcitrant disease. Most patients had approximately 30% skin surface involvement, one-third had concomitant arthritis, and the median psoriasis activity and severity index (PASI) score was 20, said Dr. Reich of Georg-August-University, Göttingen, Germany.
At week 10, 80% of patients receiving infliximab had achieved a PASI 75 score, indicating a 75% improvement in symptoms, and 57% had achieved a PASI 90 score. In comparison, only 2.6% and 1.3% of those in the placebo group had achieved PASI 75 and 90 scores, he said.
Moreover, 26% had a PASI 100, meaning there were no visible remaining signs of psoriasis, and 47% had a score of 0 on the Dermatology Life Quality Index, indicating that the disease was having no significant impact on social life or activities, he said.
At week 24, which was the conclusion of the placebo-controlled phase of the trial, 82% of patients had a PASI 75 response, and 58% had a PASI 90 response, compared with 3.9% and 1.3% of placebo-treated patients, respectively.
All patients subsequently entered the open phase of the trial. At week 50, intent-to-treat analysis showed that 61% of patients had a PASI 75 response, and a per-protocol analysis found that 71% maintained this level of response, he said.
Infliximab-treated patients also had significant improvements in nail psoriasis and in quality of life parameters at weeks 10 and 24.
“With [tumor necrosis factor] antagonists, of course, we have to take a close look at the safety profile,” Dr. Reich said. During the blinded phase of the trial, 6% and 3% of patients in the infliximab and placebo groups, respectively, experienced serious adverse events. These were primarily infections or infusion reactions, he said.
Analysis of the 1-year safety data has identified four serious infusion reactions, with angioedema, hypertension, and dizziness. There have been eight serious infections, four of which were abscesses, three were infections in the rectal area, and one was in the throat. There also have been three cases of lupuslike syndrome, two of which were serious, but no cases of congestive heart failure, tuberculosis, or demyelinating disorders.
Six malignancies have occurred, four squamous cell carcinomas, and two basal cell carcinomas. “With the skin cancers, it's hard to say if these were really related to infliximab. It could well be that the clearance of the psoriasis lesions allowed detection of the skin cancers, but this is an issue we have to follow closely,” he said.
“I think we can say that this is one of the most effective drugs we have in psoriasis,” he said, noting that the onset of effect is rapid, usually occurring between weeks 2 and 4 of treatment.
The study was funded by Centocor.