Golimumab (Centocor), an anti-TNF-alpha antibody, is being investigated for the treatment of psoriatic arthritis in a Phase 3 trial. Patients were randomized to once a month subcutaneous injection with one of two doses of golimumab or placebo. Golimumab demonstrated significant treatment benefits in outcome measures of joint, skin, and nail disease at weeks 14 and 24 along with favorable safety and tolerability
Boston - Results from a phase 3 study indicate golimumab (Centocor), a next-generation anti-tumor necrosis factor TNF-alpha monoclonal antibody, is a highly effective treatment for improving the joint and cutaneous manifestations of psoriatic arthritis, says Philip Mease, M.D., one of the psoriatic arthritis study investigators and clinical professor of medicine, University of Washington School of Medicine, Seattle.
The study enrolled 405 patients with active psoriatic arthritis, who were randomized to once-monthly subcutaneous injections of golimumab 50 mg, golimumab 100 mg, or placebo administered at weeks zero, four, eight, 12, 16 and 20.
At week 24, all placebo patients switched to golimumab 50 mg.
In the primary efficacy analysis, which was based on data collected at week 14, the two doses of golimumab provided similar efficacy in improving arthritis signs and symptoms, and both were significantly superior to placebo. Secondary outcome measures showed golimumab also significantly improved skin and nail disease at week 14, and was associated with sustained or increased benefit at week 24 in all disease findings. Golimumab was also very well-tolerated and had a favorable safety profile.
"Based on the results of this study and the findings of other trials involving different rheumatologic indications, golimumab is stacking up to be an exciting new anti-TNF agent. Compared with existing medications within this class, golimumab appears to be at least comparably effective, while it causes fewer injection site reactions than other subcutaneously administered agents and offers a more convenient dosing schedule," Dr. Mease tells Dermatology Times.
Patients were eligible for enrollment in the GO-REVEAL trial if they had at least three swollen and tender joints and active plaque psoriasis with a lesion at least 2 cm in diameter. They could be receiving stable doses of methotrexate, low-dose corticosteroids or NSAIDs, but could not have any prior treatment with an anti-TNF agent or received alefacept or efalizumab within the previous three months.
ACR20 responses (20 percent improvement in American College of Rheumatology criteria) at week 14 were analyzed as a primary efficacy endpoint in the study.
At week 14, 51 percent of patients in the golimumab 50 mg group, 45 percent of patients in the golimumab 100 mg group and 9 percent of placebo-treated controls achieved an ACR20 response.
At week 24, ACR20 responder rates were 52 percent in the golimumab 50 mg group, 61 percent in the golimumab 100 mg group and 12 percent in the placebo-treated patients.
"Results for more stringent criteria of improvement in joint disease showed approximately one-third of patients in the golimumab groups achieved an ACR50 response, compared with only 4 percent of controls, whereas about one in five golimumab-treated patients were ACR70 responders, compared with only 1 percent of the controls," Dr. Mease says.
Mean PASI scores at baseline across the three study groups ranged from 8.4 to 11.1. Evaluation of treatment effect on skin disease was based on data from patients who had at least 3 percent body surface area involvement with psoriasis at study entry.
For that subgroup, PASI75 response rates at week 14 were 40 percent in the golimumab 50 mg group, 58 percent in the golimumab 100 mg group and 3 percent in the controls.
At week 24, the PASI75 responder rate in the golimumab 50 and 100 mg groups had increased to 56 percent and 66 percent, respectively, and was only 1 percent in the placebo group.
About one-third of golimumab-treated patients achieved a PASI90 response at week 24.
Treatment effects on joint disease were also investigated using a psoriatic arthritis-modified Maastricht Ankylosing Spondylitis Enthesitis Score index and a dactylitis score. About three-fourths of patients presented with enthesitis at baseline, and both doses of golimumab afforded significant improvements in enthesitis at week 14, with further benefit seen at week 24, whereas enthesitis worsened from baseline in the control group.
The dactylitis score was significantly improved in patients treated with golimumab 100 mg, compared with placebo at week 14 and 24, and there was a trend for a significant benefit with the lower golimumab dose, Dr. Mease says.
Treatment benefits for joint disease were also seen in analyses of the Disease Activity Score 28 and in analysis of physical function measured by the Health Assessment Questionnaire.
Response of psoriasis was also demonstrated in analysis of the Nail Psoriasis Severity Index (NAPSI). At week 14, the NAPSI score improved by a mean of 28 percent in the golimumab 50 mg group, 40 percent in the 100 mg group and 7.6 percent in the controls. Mean NAPSI improvements at week 24 were 43 percent, 52 percent and 11 percent, respectively.
"Enthesitis, dactylitis and nail psoriasis are three manifestations of psoriatic arthritis that tend to be resistant to conventional oral treatments for psoriatic arthritis, " Dr. Mease says.
Serious adverse events were reported for 2 percent of golimumab-treated patients and 6 percent of placebo patients.
Disclosure: Dr. Mease is a consultant for Centocor and Swedish Medical Center, where he is research director. He receives research grants from Centocor.