Copenhagen, Denmark — Data from an open-labeled extension of a phase 3 clinical trial demonstrate that golimumab (Simponi, Centocor) provides significant long-term improvement in the signs and symptoms of psoriatic arthritis (PsA), reported investigators at the 2009 European League Against Rheumatism (EULAR) Annual Congress in Copenhagen.

Approved by the FDA in April for the treatment of moderate-to-severe psoriasis, psoriatic arthritis and ankylosing spondylitis, golimumab is an anti-TNF-alpha human monoclonal antibody administered by subcutaneous injection once every four weeks. The long-term results reported from the phase 3 psoriatic arthritis trial [Golimumab — A Randomized Evaluation of Safety and Efficacy in Subjects with Psoriatic Arthritis Using a Human Anti-TNF Monoclonal Antibody (GO-REVEAL)] were based on data available from 276 patients seen at the 104-week visit. In addition to showing sustained clinical responses, the analysis found no new safety signals.

Efficacy demonstrated

"This activity speaks to the breadth and potency of this new anti-TNF agent," says Philip J. Mease, M.D., lead study investigator and research director, Swedish Medical Center, Seattle.

"Based on my involvement in clinical trials for psoriatic arthritis and ankylosing spondylitis over the past several years, my overall impression is that golimumab is at least as potent as any of the previously available TNF antagonists, and it offers excellent tolerability along with the convenience of once-monthly administration."

The inclusion criteria for the phase 3 trial required patients to have at least three swollen and tender joints and active plaque psoriasis with a lesion at least 2 cm in diameter. Existing treatment with stable doses of methotrexate, low-dose corticosteroids or NSAIDs was allowed, but patients were excluded if they had received any treatment with a biologic agent in the previous three months.

Trial details

A total of 405 adults were initially randomized to once-weekly injections of placebo or one or two doses of golimumab (50 mg or 100 mg). Primary efficacy was evaluated at week 14 based on analyses of proportions of patients who achieved at least 20 percent improvement in arthritis signs and symptoms (ACR 20 responders). At week 16, placebo patients with an inadequate arthritis response were switched to golimumab 50 mg, while inadequate responders in the original golimumab 50 mg group were switched to golimumab 100 mg. At week 24, all remaining placebo-treated patients were switched to golimumab. After week 52, all patients became eligible to receive golimumab 100 mg based on the investigator's judgment of clinical response.

Response rates

At week 104, the ACR 20 response rates were analyzed for 70 patients who had received only golimumab 50 mg for the duration of the trial; 130 patients who received only golimumab 100 mg; and 76 patients who were switched to golimumab 100 mg after escape from the 50 mg dose. The response rates in these three cohorts were 91.4 percent, 73.1 percent and 56.6 percent, respectively. In the 50 mg and 100 mg groups, ACR 50 response rates were 67.1 percent and 53.8 percent, respectively, and ACR 70 response rates were 44.3 percent and 36.9 percent, respectively.

A total of 296 patients entered in the study had greater than 3 percent body surface area involvement with psoriasis and were evaluated for improvement in their skin disease using the Psoriatic Area and Severity Index (PASI). Of those 296 patients, 200 reached the 104-week visit.

A PASI 75 response was observed in 68.8 percent of 48 patients receiving golimumab 50 mg who did not change dose; 76.0 percent of 96 patients receiving golimumab 100 mg; and 62.5 percent of 56 patients who were switched from golimumab 50 mg to 100 mg in early escape.

"It has been reassuring as we have followed the data over time, first at week 14, then at weeks 24 and 52, and now at 104 weeks, to see efficacy has been maintained," Dr. Mease says.

"Even though the data from week 24 onward are from an uncontrolled and open-label phase, the fact that the slope of the efficacy curve, in various domains, continued to climb provides evidence for the durable benefits of golimumab."

Golimumab continued to have an acceptable safety profile as expected for an anti-TNF agent. The incidence of injection site reactions was 8 percent.

"Golimumab is remarkably well-tolerated from the perspective of injection site reactions, and this attribute may be explained by the very small volume administered, as well as to the vehicle formulation.

With this low rate of injection site reactions, combined with the once-a-month administration schedule, golimumab is associated with very high patient acceptance," Dr. Mease says.

Adverse events

Serious adverse events occurred in 9 percent of patients. There were no reports of tuberculosis. Histoplasmosis occurred in one golimumab-treated patient living in an endemic area, but the infection was successfully treated.

Malignancies included single cases of basal cell skin cancer, colon cancer and small cell lung cancer in patients receiving golimumab 50 mg. In the higher-dose group, two patients developed basal cell skin cancer, one patient was diagnosed with prostate cancer and one with small cell lung cancer. The latter patient died during the study and was the only death other than an accident-related fatality.

"The current long-term data from GO-REVEAL represent great news for patients with psoriatic arthritis and the physicians who treat them. Golimumab offers effective and convenient treatment that can be used as another option for first-line anti-TNF therapy or to manage patients who are not responding to or are experiencing adverse effects associated with existing treatment," Dr. Mease says.

Disclosure: Dr. Mease is a consultant for Centocor, and Swedish Medical Center receives research grants from Centocor.