Efficacy of Golimumab for Refractory RA Maintained Over 5 Years

San Diego—Long-term outcomes show that golimumab maintains its efficacy for patients with active rheumatoid arthritis (RA) who failed prior biologic therapy with anti-tumor necrosis factor (TNF) therapy.

These were the results of the 5-year GO-AFTER (Golimumab in Patients with Active Rheumatoid Arthritis after Treatment with Tumour Necrosis Factor Alpha Inhibitors) trial, presented at the ACR/ARHP meeting during a poster session by Josef S. Smolen, MD, division of rheumatology, department of medicine III, Medical University of Vienna and Hietzing Hospital, Vienna, Austria, lead study researcher.

The GO-AFTER trial is the first multicenter, randomized, placebo-controlled trial that evaluated the safety and efficacy of golimumab in patients with active RA. Of the patients enrolled in the trial, 66% had failed 1 prior anti-TNF agent, 25% had failed 2 prior anti-TNF agents, and 9% had failed 3 prior anti-TNF agents.

In the study, patients were first randomized to receive placebo, golimumab 50 mg, or golimumab 100 mg every 4 weeks. At week 16, patients who failed to achieve an adequate treatment response (ie, <20% improvement from baseline in swollen and tender joint counts) entered, in a double-blinded way, early escape, from placebo to golimumab 50 mg, or golimumab 50 mg to golimumab 100 mg.

At week 24, the start of the long-term extension part of the study, patients still on placebo were switched to golimumab 50 mg and all other patients continued on their current treatment. The trial was unblinded after the last patient completed week 24. At investigator discretion, patients were permitted a 1-time increase or decrease of golimumab dose and the last injection of golimumab was at week 252.

Dr. Smolen reported on the observed efficacy results through week 256 and cumulative safety data reported through week 268. Efficacy outcomes were based on American College of Rheumatology (ACR) 20/50/70, disease activity score 28 based on C-reactive protein DAS28-CRP, and clinical disease activity index (CDAI).

Of the 471 patients randomized, 459 received golimumab. Of these, 183 continued treatment through week 252, while 276 withdrew from the study. Reasons for withdrawal included adverse events (n=86), lack of efficacy (n=107), lost to follow-up (n=9), death (n=5), and other reasons (n=69).

The study found that at week 256, 60.3% of all patients with available efficacy data had an ACR20, 42.3% had an ACR50, 21.7% had an ACR70, 29% had DAS28-CRP <2.6, and 16.0% had CDAI <2.8. 

Safety data through week 268 showed that 151 of 431 patients had a serious adverse event, with rates of serious infection, malignancies, and death seen in 13.9% of patients treated with golimumab 50 mg, 4.6% in patients treated with golimumab 50 mg and 100 mg, and 2.1% in patients treated with golimumab 100 mg.

The most common adverse events were upper respiratory tract infections, sinusitis, and nasopharyngitis (27.1%, 17.1%, and 16.9%, respectively). Overall, 12.3% of patients had >1 injection-site reaction. The study also found that 31 of 388 patients (8%) with available samples tested positive for antibodies to golimumab.

According to the investigators, the efficacy of golimumab is maintained through 5 years in refractory RA patients, and the safety of golimumab is consistent with the safety profile reported with other anti-TNF agents.

Limitations of the study highlighted by the investigators included the lack of good control group after week 24 (the study was an open label study after week 24), the potential for biased outcomes based on the use of observed data for analysis (patients responding well may have stayed in the trial), and the allowance in the trial for patients to change dosing of golimumab treatment at their physician’s discretion.