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

Background: The safety and efficacy of s.c. golimumab (GLM)+/-MTX has been evaluated through 2 years in a phase 3 trial (GO-FORWARD) of pts with active RA despite MTX therapy. Final safety and efficacy results through 5 years 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 weeks 16 (blinded early escape) or 24 (crossover). Pts continued treatment at week 52 (start of long-term extension). After the last pt completed week 52 and unblinding occurred, MTX and corticosteroid use could be adjusted, and a one-time GLM dose increase (50 to 100 mg) or decrease (100 to 50 mg) was permitted based on investigator judgment. The last GLM injection was at week 252. Observed efficacy results (ACR20/50/70, DAS28-CRP, HAQ-DI, radiographic) by randomized treatment group and cumulative safety data are reported through weeks 256 and 268, respectively. Results: A total of 444 pts were randomized; 313 pts continued treatment through week 252, 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 week 268. At week 256, 76.0% of all pts had an ACR20, 89.5% had a DAS28-CRP EULAR response, and 68.5% had improvement in HAQDI ≥0.25. Changes from baseline in mean total vdH-S scores were small; 54% of pts randomized to GLM+MTX had no radiographic progression (ΔvdH-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 week 268, 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 5 years. The long-term safety of GLM is consistent with other anti-TNFα agents.