Alefacept plus methotrexate for psoriatic arthritis

Abstract

Background Psoriatic arthritis (PsA) is a multifactorial condition that leads to chronic inflammation of the joints and entheses in around 10–30% of patients with psoriasis. Therapy for PsA is generally based around agents used to treat rheumatoid arthritis (RA), but toxicity and variability in treatment response limit their use, especially in the long term. Following recent research into the underlying immunologic nature of PsA, interest has focused on the modification of T-cell function. Alefacept, an inhibitor of T-cell activation approved for the treatment of chronic plaque psoriasis, has shown promising results in pilot studies in PsA. Objectives To investigate the efficacy and safety of alefacept in combination with methotrexate for the treatment of PsA. Design This was a placebo-controlled, double-blind, international phase II clinical trial. Eligible patients were 18–20 years old, with active PsA (greater than or equal to3 swollen joints and greater than or equal to3 tender joints), and were receiving stable doses of methotrexate (total duration of methotrexate treatment greater than or equal to3 months). Intervention Patients received weekly doses of either alefacept 15 mg or placebo intramuscularly for 12 weeks. This was followed by a 12-week, methotrexate-only observation period. All patients continued on their stable methotrexate dose (10–25 mg/week) throughout. Patients were stratified according to psoriasis body surface area (BSA) involvement (greater than or equal to3% or <3%) at baseline. Outcome measures The main study outcome was the proportion of patients achieving an ACR20 response (20% improvement in disease activity according to the American College of Rheumatology criteria) at week 24. Other outcome measures included changes in psoriasis BSA involvement, and safety parameters. Results In all, 185 patients were included in the study (alefacept n = 123, placebo n = 62). At week 24, significantly more patients in the alefacept group achieved an ACR20 response, compared with patients in the placebo group (54% vs 23%, respectively, P <0.001). Patients in the alefacept group showed a significantly greater decrease in tender joints (31%, mean reduction -8.0) and in swollen joints (46%, mean reduction -6.3), compared with patients in the placebo group (17%, mean reduction -4.5, and 35%, mean reduction -3.5, respectively). In the alefacept group, significantly more patients with psoriasis involving greater than or equal to3% of BSA showed a 50% reduction in psoriasis severity at week 14 compared with patients in the placebo group (53% vs 17%, respectively, P <0.001). Reported adverse events were mild-to-moderate in severity and similar in both groups. The incidence of serious adverse events was low (1.6%) and judged to be unrelated to study medication. Conclusion The results of this study suggest that alefacept in combination with methotrexate might be effective and safe for the treatment for PsA.