Background/Purpose: Patients (pts) with rheumatoid arthritis (RA) often experience both substantial fatigue and a decline in their health-related physical and emotional well-being. Sirukumab is a human anti-IL-6 monoclonal antibody that selectively binds to the cytokine with high affinity, and is under development for RA and a number of other diseases. The effects of sirukumab on health-related physical and emotional well-being and fatigue were evaluated in 2 separate randomized, double-blind, placebo-controlled, multicenter global phase 3 studies in pts with RA refractory to conventional DMARDs (SIRROUND-D) or refractory or intolerant to anti-TNF therapy (SIRROUND-T). Pts may have been taking other biologics prior to both studies.

Methods: In both studies, eligible pts were randomized (1:1:1) to treatment with SC sirukumab 50 mg q4w, 100 mg q2w, or placebo q2w. The placebo-controlled portions of SIRROUND-D and -T were 52 and 24 wks, respectively; thus, results from both studies were examined at Wk 24 and are presented here. The primary objective of both studies was to evaluate the efficacy of sirukumab in the study-specific RA pt populations. Health-related physical and emotional well-being were evaluated as secondary endpoints using the SF-36 health survey, and fatigue evaluated using the FACIT-Fatigue scale. For SF-36 physical and mental component summary (PCS and MCS) scores, clinically meaningful improvement was defined as a ≥5-point increase from baseline (BL); for FACIT-Fatigue, clinically meaningful improvement was defined as a ≥4-point increase from BL.  

Results:  A total of 1,670 and 878 pts in SIRROUND-D and -T, respectively, had evaluable data. In both studies, increases (improvements) from BL at Wk 24 in mean SF-36 PCS and MCS scores and all 8 SF-36 domain scores were significantly greater with either sirukumab dose level (50 mg q4w or 100 mg q2w) versus placebo (all P<0.02; Table). Similarly across both studies, significantly greater mean increases (improvements) from BL at Wk 24 were observed in the FACIT-Fatigue score with sirukumab (either dose) versus placebo (all P<0.001 [not adjusted for multiplicity]; Table). Improvements in SF-36 and FACIT-Fatigue scores with both sirukumab doses versus placebo were observed at Wk 8 through all time points to Wk 24 in both studies. In addition, across studies, the percentages of pts who achieved clinically meaningful improvements from BL at Wk 24 in SF-36 PCS and MCS scores, and in FACIT-Fatigue score were significantly higher with sirukumab (either dose) versus placebo (all P<0.02).

Conclusion: Treatment with sirukumab was associated with significant and clinically meaningful improvements from BL in health-related physical and emotional well-being and fatigue for pts with active RA who had not responded adequately to prior treatment, regardless of whether prior treatment was with conventional DMARDs or TNF inhibitors.