Golimumab in combination with methotrexate in Japanese patients with active rheumatoid arthritis: results of the GO-FORTH study

Abstract

Objective: To assess the efficacy and safety of golimumab + methotrexate (MTX) in Japanese patients with active rheumatoid arthritis (RA).

Methods: 269 Japanese patients with active RA despite treatment with MTX were randomised (1:1:1) to placebo + MTX (Group 1), golimumab 50 mg + MTX (Group 2) or golimumab 100 mg + MTX (Group 3). Subcutaneous golimumab/placebo was injected every 4 weeks; stable doses of oral MTX (6-8 mg/week) were continued. Patients were allowed to enter early escape (Group 1 added golimumab 50 mg, Group 2 increased golimumab to 100 mg, Group 3 continued golimumab 100 mg) based on swollen/tender joint counts at week 14. The primary study endpoint was achievement of at least 20% improvement in the American College of Rheumatology (ACR20) response criteria at week 14. To control for multiplicity of testing, treatment group comparisons were first made between combined Groups 2 and 3 versus Group 1, followed by comparisons of Group 2 and Group 3 versus Group 1.

Results: The proportion of patients with an ACR20 response at week 14 was significantly higher in combined Groups 2 and 3 (73.4%, 127/173) and in each of Group 2 (72.1%, 62/86) and Group 3 (74.7%, 65/87) compared with Group 1 (27.3%, 24/88; p<0.0001 for all comparisons). Golimumab + MTX also elicited a significantly better response than placebo + MTX in other efficacy parameters, including disease activity score (DAS28) response/remission and radiographic assessments. During the 16-week fixed treatment regimen study period, 72.7%, 75.6% and 78.2% of patients had adverse events and 1.1%, 1.2% and 2.3% had serious adverse events in Groups 1, 2 and 3, respectively.

Conclusion: In Japanese patients with active RA despite MTX therapy, golimumab + MTX was significantly more effective than MTX monotherapy in reducing RA signs/symptoms and limiting radiographic progression with no unexpected safety concerns.

Trial registration: ClinicalTrials.gov NCT00727987.

Figure 1

Patient disposition through week 24; randomised patients. Note that ‘worsening of rheumatoid arthritis’ is included in ‘unsatisfactory therapeutic response’ and not as an AE. AE, adverse event; EE, early escape; pts, patients.

Figure 2

(A) American College of Rheumatology 20% (ACR20), (B) 50% (ACR50) and (C) 70% (ACR70) improvement from baseline through week 24. Note that patients who met the early escape criteria at week 16 and crossed over to golimumab 50 mg or dose escalated from golimumab 50 mg to 100 mg are shown with an open triangle and closed circle, respectively. For the 28 patients in the placebo + MTX group and the nine patients in the golimumab 50 mg + MTX group who met the early escape criteria, week 20 and 24 data were imputed using last observation carried forward methodology, as were other missing data. As such, 88 patients in the placebo + MTX group and 86 patients in the golimumab 50 mg + MTX group were included in these data displays. MTX, methotrexate.

Figure 3

Proportions of patients achieving at least 20%, 50% and 70% improvement in the American College of Rheumatology (ACR20, ACR50, ACR70) response criteria by serum golimumab concentration quartiles (µg/ml) at week 24. The results are from a post hoc analysis of ACR responders in the combined Group 2 (golimumab 50 mg + MTX) and Group 3 (golimumab 100 mg + MTX). MTX, methotrexate.