Background/Purpose: In the SIRROUND-D study, sirukumab (SIR), a human monoclonal antibody that selectively binds to the IL-6 cytokine with high affinity, significantly reduced radiographic progression after 52 wks compared with placebo (PBO) in patients (pts) with active rheumatoid arthritis (RA) despite DMARD treatment.  Long-term data on radiographic progression after 104 wks of SIR treatment are presented.

Methods: In this Phase 3 study, 1,670 pts with moderate to severe active RA, defined as ≥6/66 swollen and ≥6/68 tender joints and a minimum CRP ≥8.0 mg/L, that was refractory to DMARDs were randomized (1:1:1) to SC SIR 50 mg q4w, SIR 100 mg q2w, or PBO q2w.  Pts randomized to PBO who had <20% improvement in swollen/tender joints at Wks 18 or 40 or were still taking PBO at Wk 52 were re-randomized to SIR; blinded treatment lasted 104 wks. Images of the hands and feet were taken at baseline, Wks 18 (early escape [EE] criteria met), 24 (EE criteria not met), 52, and 104.  For this analysis of radiographic change over the second year of SIRROUND-D, only images taken at baseline, Wk 52, and after Wk 52 (eg, Wk 104) were evaluated.  The endpoints included changes from baseline at Wks 52 and 104 in the modified Sharp/van der Heijde score (SHS) for radiographic damage, erosion score, and joint space narrowing (JSN) score and the proportions of pts with radiographic progression (change >smallest detectable change [SDC]) and with a change of ≤0 from baseline in SHS.  Analyses only included pts who were still on study treatment at Wk 52 and had non-missing SHS score at both baseline and Wk 52. All analyses were based on observed data unless noted.

Results: A high proportion of pts had readable images at baseline, Wk 52, and post-Wk 52, ranging from 94.5% to 97.1%.  Of 1218 pts who had not terminated the study or study treatment early, 1176 had evaluable Wk 104 x-rays.  The mean change from baseline in the SHS at Wk 104 generally increased slightly versus Wk 52; changes from baseline at Wks 52 and 104 remained below the SDC for SHS scoring for pts originally randomized to SIR (both doses; Table).  Mean changes in the SHS from Wk 52 to Wk 104 were negligible across all treatment groups. Similar results were observed for the erosion and JSN scores (Table).  At Wks 52 and 104, the proportions of pts with radiographic progression based on SHS were similar for both SIR doses among pts randomized to SIR and those randomized to PBO who crossed over to SIR.  The proportions of pts with a change in SHS of ≤0 were generally comparable for both SIR doses among pts randomized to SIR and those randomized to PBO who crossed over to SIR at Wks 52 and 104.

Conclusion: Treatment with SIR 50 mg q4w and SIR 100 mg q2w in pts with active RA despite DMARD therapy resulted in minimal radiographic progression over 2 years, indicating that inhibition of joint damage by SIR demonstrated at Wk 52 was maintained through Wk 104 of this study.