Background/Purpose: Sirukumab, a selective, high-affinity, human anti–IL-6 monoclonal antibody, is in development for rheumatoid arthritis (RA) and other diseases.  Effects of sirukumab on RA symptoms and disease activity and health-related physical and emotional well-being were evaluated in 2 phase 3 randomized controlled trials (RCTs) in RA pts with inadequate responses to conventional DMARDs (SIRROUND-D) or TNF inhibitors (TNFi; SIRROUND-T).  Across both RCTs, significant improvements were observed in all 8 SF-36 domains with both evaluated sirukumab doses (50 mg q4w and 100 mg q2w) versus placebo (PBO; P<0.001).

Methods: In both RCTs, eligible pts were randomized (1:1:1) to treatment with SC sirukumab 50 mg q4w, sirukumab 100 mg q2w, or PBO.  Durations of PBO treatment were 52 and 24 wks, respectively, in SIRROUND-D and SIRROUND-T.  Efficacy of sirukumab was evaluated using traditional RA endpoints.  This analysis included SDAI and CDAI scores and the following patient-reported outcomes (PROs): pt global assessment of disease activity, pain (0-10 VAS), HAQ-DI, FACIT-Fatigue, and SF-36 health survey.  In this post-hoc analysis, correlations between changes from baseline (BL; at Wks 16 [primary endpoint] or 24) in disease activity, symptoms, and SF-36 domain scores were evaluated.  Last observation carried forward was used for imputing missing data.

Results: For changes from BL to Wk 16 in SIRROUND-T, correlation coefficients (r) were low to moderate between all 8 SF-36 domains and SDAI (r ranging from −0.535 to −0.208) and CDAI (−0.526 to −0.209; Table).  Low to moderate correlations were also observed between changes from BL to Wk 16 in 7 of 8 SF-36 domains and pt global assessment scores (r ranging from −0.461 to −0.267) in SIRROUND-T, and a high correlation was observed for the remaining domain, bodily pain (−0.665 to −0.619).  Moderate correlations were observed between changes from BL to Wk 16 in the SF-36 bodily pain, physical function, social function, and role-physical domains and changes in HAQ-DI (r ranging from −0.560 to −0.310).  Moderate to high correlations were observed for changes from BL to Wk 16 in 7 of 8 SF-36 domains and FACIT-Fatigue scores (r ranging from 0.392 to 0.627; Table).  As anticipated, changes from BL to Wk 16 in VAS pain and SF-36 bodily pain domain were highly correlated (r ranging from −0.672 to −0.661; Table).  Correlations were generally higher with sirukumab than placebo.  Similar correlations were observed in changes from BL to Wk 16 in SIRROUND-D.  These correlations were maintained at Week 24 in both RCTs.

Conclusion: Results of these analyses highlight the importance of PROs, including SF-36 and FACIT-Fatigue, as independent measures of treatment success.  Although some SF-36 domains are moderately correlated with clinical responses, these findings indicate that SF-36 captures aspects of patient well-being not covered by standard measures of RA symptoms and disease activity.