CHICAGO — The combination of methotrexate and alefacept appears to be safe and effective for the treatment of psoriatic arthritis, Mark G. Lebwohl, M.D., said at the 11th International Psoriasis Symposium, sponsored by the Skin Disease Education Foundation.
This is the first study to evaluate alefacept in combination with methotrexate in psoriatic arthritis, which affects about 20%–30% of all psoriasis patients.
Alefacept (Amevive) is approved for psoriasis and demonstrated clinical improvement in an initial pilot in psoriatic arthritis.
In this double-blind study, 185 patients aged 18–70 years with active psoriatic arthritis despite methotrexate treatment for 3 or more months were randomized to 15-mg alefacept once weekly for 12 weeks or placebo. All patients continued on methotrexate at various dosages.
At week 14, 53% of patients in the alefacept group achieved a 50% or greater improvement according to scores on the Psoriasis Area and Severity Index (PASI 50), compared with 17% of the placebo group.
At week 24, 54% of the alefacept/methotrexate-treated patients achieved at least a 20% improvement according to American College of Rheumatology response criteria (ACR 20), compared with 23% of the investigation participants who received methotrexate plus placebo.
Results on both efficacy end points were statistically significant, he said.
The incidence of serious adverse events was 2%, and no serious infections or malignancies were reported in the alefacept-treated group.
Longer-term data for psoriasis shows no increase in malignancies or infections, Dr. Lebwohl noted in an interview. This suggests that the combination of alefacept and methotrexate may be useful in the long-term management of psoriatic arthritis.
In addition to greater efficacy, it's hoped that the combination therapy would allow for reduced methotrexate dosages, he said.
Two other biologic therapies, etanercept and infliximab, have both been used with methotrexate in rheumatoid arthritis, allowing for a reduction in the required dosage of methotrexate.
The rationale for using alefacept is that it selectively reduces memory T-cells, which may play a role in the pathogenesis of psoriatic arthritis, said Dr. Lebwohl, chair of dermatology at Mt. Sinai School of Medicine, New York.
Synovial fluid analyses from psoriatic arthritis patients have shown a reduction in CD4+ and CD8+ cells from baseline following treatment with alefacept. Other T-cell therapies, such as cyclosporine, also have shown some benefit in psoriatic arthritis patients.
Although it's not surprising that therapies targeting T cells might be of benefit in psoriatic arthritis, Dr. Lebwohl noted that a recent efalizumab (Raptiva) trial involving psoriatic arthritis patients did not show similar significant benefits.
Dr. Lebwohl is a consultant, speaker, and investigator for Biogen Inc., which markets alefacept. The SDEF and this newspaper are wholly owned subsidiaries of Elsevier.