Background/Purpose: Ultrasound (US) is an established non-invasive tool for sensitively assessing disease activity at the individual‐joint level in rheumatoid arthritis (RA). Synovial thickness is detectable on grey-scale US and synovial vascularity by power Doppler US (PDS).¹ Studies have shown that PDS correlates with clinical assessment of disease activity and synovial histopathology.² Furthermore, PDS can detect subclinical synovitis.³ Sirukumab (SIR), a human monoclonal antibody that selectively binds to IL-6 with high affinity, demonstrated efficacy in RA in several phase 3 studies including SIRROUND-H (active comparator monotherapy study). The ability of grey-scale US and PDS to evaluate changes in synovitis was assessed following SIR and adalimumab (ADA) treatment in patients (pts) with moderate to severe RA in a substudy of SIRROUND-H.

Methods: In SIRROUND-H, US assessment was carried out at 9 clinical sites in a nested subset of 41 pts, with 27 pts pooled from SIR 50mg q4w/SIR 100mg q2w and 14 pts in the ADA 40mg q2w treatment groups. Assessments were performed at baseline (BL), and Wks 2, 4, 8 and 24. 12 joints (10 metacarpal [MCP] plus wrists) were evaluated and synovial vascularity (VASCi), thickness (STI) and tenosynovitis/hyperemia (wrist) scores were reported for each timepoint. Significance of differences between baseline and post-treatment timepoints were tested using Wilcoxon signed-rank and Mann-Whitney tests (α=0.05).

Results: BL VASCi and STI scores correlated with BL disease activity (DAS28[CRP], CDAI, and swollen and tender joint counts). Pts who were ACPA and RF positive had significantly higher BL VASCi and STI scores. Initial analysis of post-treatment changes in PDS outcomes showed no significant differences from BL at the population level. However, a significant proportion of the study cohort (36.6% or 15/41) had a BL VASCi score <1, leaving little room for evaluable improvement. When the analysis of post-treatment changes was restricted to pts with a BL VASCi >1 (n=26), both SIR and ADA treatment showed significant reductions in VASCi starting at Wk 4 and sustained through Wk 24 (P<0.05 vs BL). Wk 24 DAS remission was associated with lower BL VASCi and STI (P<0.05). The Wk 24 changes in VASCi and STI did not correlate with Wk 24 DAS28(CRP) or DAS28(ESR) changes from baseline. STI was not changed with SIR or ADA treatment over the course of the study duration (24 wks) and there was no observed difference in effect on vascularity or thickness between patients treated with SIR vs ADA.

Conclusion: Our study demonstrates the utility of non-invasive PDS of small joints to detect synovial changes following drug treatment in RA patients with high baseline VASCi scores. Both SIR and ADA similarly improved VASCi scores from Wk 4. A correlation between changes in PDS score and disease activity was not observed in this small substudy, consistent with reports in the literature.³ In conclusion, PDS can detect changes in joint pathology with treatment and is feasible for use in global clinical studies.

References:

1. Taylor PC, et al. Arthritis Rheum. 2004;50:1107-1116.
2. Mandl P, et al. Rheumatology. 2014;53:2136-2142.
3. Bhasin S, et al. Dis Markers. 2015;2015:325909.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/sirukumab-improves-synovial-vascularity-as-measured-by-power-doppler-sonography-in-rheumatoid-arthritis-patients-from-as-early-as-week-4-in-a-phase-3-trial/