Intravenous Golimumab Inhibits Radiographic Progression and Maintains Clinical Efficacy and Safety in Patients with Active Rheumatoid Arthritis Despite Methotrexate Therapy: 1-Year Results of a Phase 3 Trial

Background/Purpose: To evaluate long-term clinical/radiographic efficacy of IV golimumab(GLM) 2mg/kg+MTX in pts with active RA despite MTX through wk 52.

Methods: Pts (n=592) with active RA (≥6/66 swollen joints, ≥6/68 tender joints, CRP≥1.0mg/dL, RF and/or anti-CCP positive at screening) despite ≥3months of MTX(15-25mg/wk) participated in this multicenter, randomized, double-blind, placebo(PBO)-controlled study. Pts were randomized to IV GLM 2mg/kg or PBO at wks0&4 and q8wks; all pts continued stable MTX. Pts randomized to PBO with <10% improvement in SJC+TJC at wk16 could early escape to IV GLM 2mg/kg (wks16&20, q8wks). All PBO pts received IV GLM 2mg/kg starting at wk24. Primary study endpoint was wk14 ACR20 response; major secondary clinical efficacy endpoints are reported through wk24. Radiographs of hands and feet were taken at baseline, wk24(wk16 for early escape) and wk52 and were scored by 2 independent readers and adjudicator (as needed) using modified vdHS score.
Results:  Baseline demographic and disease characteristics were comparable between grps. 93% of pts (553/592) continued through wk52. 39 pts d/c, mostly due to AEs(18 pts).GLM+MTX-tx pts demonstrated significantly (sig) less radiographic progression (total vdHS+subscores) vs PBO+MTX at wk24. Pts randomized to PBO+MTX who began GLM at wk16/24 demonstrated marked slowing of radiographic progression, to the same rate as pts randomized to GLM, from wk24 to wk52. At wk14, sig (p<0.001) larger proportions of GLM+MTX vs PBO+MTX pts achieved ACR20,  DAS28-CRP good/moderate , ACR50 and ACR70 responses and greater median improvement in HAQ score (0.50vs0.13). Through wk52, ACR20, ACR50, ACR70, and DAS28 good/moderate response rates in pts randomized to GLM+MTX were 66%, 39%, 18%, and 81%, resp. Among pts who achieved ACR20, ACR50, ACR70 and DAS28 good/moderate responses by wk24, 82%, 72%, 61%, and 88%, resp, maintained response through wk52. Through wk52, all GLM-tx pts were followed for an average of 44wks. AEs and serious AEs occurred in 65% and 9%, resp, of GLM-tx pts (vs 43% and 4% at wk24). 1 case of TB and no serious opportunistic infections were reported through wk52. 1 pt receiving GLM+MTX (0.16%) died. Through wk52, the proportions of infusions and pts with infusion reactions were 0.7% and 3.6%, resp, (vs 1.1% and 3.5% at wk24).
Conclusion: GLM+MTX sig inhibited radiographic progression (for total vdHS and subscores) at wk24&52. Among PBO-tx pts who began GLM at wk16/wk24, marked slowing of radiographic progression, to the rate in pts randomized to GLM, was observed from week 24 to wk52. IV GLM+MTX sig improved and maintained RA signs/symptoms in pts with active RA despite ongoing MTX and continued to demonstrate an acceptable safety profile through wk52.