Briakinumab was more effective than methotrexate at reducing the signs and symptoms of moderate to severe plaque psoriasis in a 52-week, phase-III study reported in the Oct. 27 issue of the New England Journal of Medicine.
However, serious adverse events, adverse events leading to withdrawal from the study, serious infections, and cancers occurred more often with briakinumab, a monoclonal antibody that targets the "p40 molecule shared by interleukin-12 and interleukin-23, which is overexpressed in psoriatic skin lesions," according to Dr. Kristian Reich, medical director of the Dermatologikum Hamburg, and his associates. However, "Too few patients were enrolled in the study to draw conclusions regarding these adverse events."
In the study, conducted at 43 sites in Europe and Canada and funded by Abbott Laboratories, 317 patients with stable plaque psoriasis were randomly assigned to receive subcutaneous briakinumab (154 subjects) or oral methotrexate plus oral folate (163 subjects) in a double-blind fashion. Efficacy was assessed at week 24 and week 52 (N. Engl. J. Med. 2011;365:1586-96).
Significantly more patients in the briakinumab group showed at least a 75% improvement in their score on the psoriasis area and severity index (PASI) at both week 24 (81.8%) and week 52 (66.2%), compared with patients on methotrexate (39.9% at week 24 and 23.9% at week 52). The median time to such improvement was 56 days with briakinumab, compared with 140 days with methotrexate.
In addition, "the percentage of patients who had at least 75% improvement in the PASI score was significantly greater in the briakinumab group than in the methotrexate group by week 4 and at all time points through week 52," Dr. Reich and his colleagues reported.
The difference between the two groups became significant at week 2, and the difference in the proportion of patients showing 90%-100% improvement became significant at week 8.
Also, significantly more patients who received briakinumab met the efficacy end point of a score of 0-1 on a 5-point measure of the physician’s global assessment at both week 24 (80.5% vs. 34.4%) and week 52 (63.0% vs. 20.2%). Significantly more patients receiving briakinumab (46.1%) than methotrexate (9.2%) had a score of 0, indicating complete clearing at week 24, with similar results at week 52 (45.5% vs. 9.8%, respectively).
The median time to achieving a score of 0-1 on the physician’s global assessment was 69 days with briakinumab, compared with 171 days with methotrexate. And significantly more patients in the briakinumab group had a score of 0-1 at every time point from week 4 through week 52.
On the Dermatology Quality of Life Index, which measures the impact of skin disease on quality of life, more patients taking briakinumab (70.8%) than methotrexate (34.4%) had a score of 0-1, indicating minimal impact at week 24, as well as at week 52 (61.7% vs 17.8%, respectively). And significantly more patients taking briakinumab had a clinically meaningful reduction in Dermatology Quality of Life Index score at all time points.
In all, 12 patients in the briakinumab group (7.8%) and 10 in the methotrexate group (6.1%) withdrew from the study because of adverse events. The incidence of serious infections was 4.1 per 100 patient-years with briakinumab and 2.7 per 100 patient-years with methotrexate.
The four serious infections with briakinumab included one case of legionella with candidemia and septic shock, one case of osteomyelitis, one case of herpes zoster, and one case of tonsillitis. In the methotrexate group, there were two cases of diverticulitis and one case of hepatitis.
Three patients in the briakinumab group were diagnosed with cancer. And one death was reported: a patient receiving methotrexate died from an esophageal rupture.
This study was supported by Abbott, maker of briakinumab. Dr. Reich and his associates reported ties to Amgen, Astellas Celgene, Centocor, Biogen-Idec, Galderma, Janssen-Cilag, Graceway, Johnson & Johnson, LEO-Pharma, Meda-Pharma, Merck, Novartis, Ortho Biotech, Pfizer, Schering-Plough, UCB, and Wyeth.