Golimumab in patients with active rheumatoid arthritis after treatment with tumor necrosis factor α inhibitors: findings with up to five years of treatment in the multicenter, randomized, double-blind, placebo-controlled, phase 3 GO-AFTER study

Abstract

Introduction: The aim of this study was to assess long-term golimumab therapy in rheumatoid arthritis (RA) patients who discontinued previous tumor necrosis factor-α (TNF)-inhibitor(s).

Methods: Patients enrolled into this multicenter, randomized, double-blind, placebo-controlled study of active RA (≥4 tender, ≥4 swollen joints) received placebo (Group 1) or golimumab 50 mg (Group 2) or 100 mg (Group 3) injections every 4 weeks. Patients in Groups 1 and 2 with inadequate response at week 16 escaped to golimumab 50 and 100 mg, respectively. At week 24, Group 1 patients crossed-over to golimumab 50 mg, Group 2 continued golimumab 50/100 mg per escape status, and Group 3 maintained dosing. During the long-term-extension (LTE), golimumab 50 mg could be increased to 100 mg, and 100 mg could be decreased to 50 mg. Data through 5 years are reported for all patients (safety) and patients using methotrexate (efficacy, intention-to-treat (ITT) analysis with last-observation-carried-forward for missing data and non-responder imputation for unsatisfactory efficacy discontinuations).

Results: In total, 459 of 461 randomized patients received the study agent, 304 of whom were methotrexate-treated and included in efficacy analyses. Through week 256, the proportions of methotrexate-treated patients achieving American-College-of-Rheumatology (ACR) responses were 37.6% to 47.0% for ACR20, 21.4% to 35.0% for ACR50, and 7.8% to 17.0% for ACR70 response across randomized groups. Golimumab safety through week 268 was generally consistent with that at week 24 and week 160 and other anti-TNF agents.

Conclusions: In some patients with active RA discontinuing previous TNF-antagonist therapy, golimumab safety and efficacy, assessed conservatively with ITT analyses, was confirmed through 5 years.

Trial registration: Clinicaltrials.gov NCT00299546 . Registered 03 March 2006.

Figure 1

Clinical efficacy over time through week 256. ACR20 (A), ACR50 (B), DAS28-CRP response (C), DAS28-CRP score <2.6 (D), DAS28-CRP score <3.2 (E), SDAI score ≤3.3 (F), and HAQ-DI improvement ≥0.25 (G). Data summarized for randomized patients receiving methotrexate at baseline, excluding one site, using intent-to-treat methodology, with replacement of missing data by last-observation-carried forward methodology and imputation with baseline median values, and nonresponder imputation for discontinuations due to unsatisfactory therapeutic effect. ACR20/50, ≥20%/50% improvement in the American College of Rheumatology response criteria; CRP, C-reactive protein; DAS28, 28-joint Disease Activity Score; HAQ-DI, Health Assessment Questionnaire Disability Index; SDAI, Simplified Disease Activity Index.