Final 5-Year Safety and Efficacy Results Of a Phase 3, Randomized Placebo-Controlled Trial Of Golimumab In Patients With Active Rheumatoid Arthritis Despite Prior Treatment With Methotrexate

Abstract

Background/Purpose: The safety and efficacy of subcutaneous golimumab (GLM)+/-MTX has been evaluated through 2yrs in a phase 3 trial (GO-FORWARD) of pts with active rheumatoid arthritis (RA) despite MTX therapy. Final safety and efficacy results through 5yrs are reported.

Methods: Pts in GO-FORWARD were randomized to placebo(PBO)+MTX, GLM 100mg+PBO, GLM 50mg+MTX, or GLM 100mg+MTX q4w. PBO+MTX pts crossed over to GLM+MTX at wks 16 (blinded early escape) or 24 (crossover). Pts continued treatment at wk52 (start of long-term extension). After the last pt completed wk52 and unblinding occurred, MTX and corticosteroid use could be adjusted, and a one-time GLM dose increase (50 à100mg) or decrease (100 à50mg) was permitted based on investigator judgment. The last GLM injection was at wk252. Observed efficacy results (ACR20/50/70, DAS28-CRP, HAQ-DI, radiographic) by randomized treatment group and cumulative safety data are reported through wks 256 and 268, respectively.

Results: A total of 444 pts were randomized; 313 pts continued treatment through wk252, and 131 pts withdrew (64 for AE, 25 for lack of efficacy, 1 protocol violation, 6 lost to follow-up, 32 for other reasons, 3 deaths). 301 completed the safety follow-up through wk268. Efficacy results are presented in the table. At wk256, 76.0% of all pts had an ACR20, 89.5% had a DAS28-CRP EULAR response, and 68.5% had improvement in HAQ-DI ≥0.25. Changes from baseline in mean total vdH-S scores were small; 54% of pts randomized to GLM+MTX had no radiographic progression (DvdH-S≤0). The most common AEs were upper respiratory tract infection (32.9%), nasopharyngitis (17.1%), and bronchitis (17.1%); 9.2% of pts had an injection-site reaction. Through wk268, 172/434 pts (39.6%) had an SAE; 14.1% of pts discontinued study agent due to AEs. The rates of serious infections, malignancies, and death were 11.5%, 6.2%, and 1.8%, respectively. Of 429 pts with available samples, 33 (7.7%) were positive for antibodies to GLM.

Conclusion: The retention rate was high (70.5%), and improvements in signs/symptoms of RA and in physical function with GLM+MTX therapy were maintained long-term. Radiographic progression appeared controlled with small changes in mean vdH-S scores observed through 5yrs. The long-term safety of GLM is consistent with other anti-TNFα agents.