Impact of Scleroderma-Associated Autoantibodies on Clinical Outcome Assessments: Post Hoc Analysis From a Randomised, Double-blind, Placebo-controlled, Phase 3 Trial of Tocilizumab in Scleroderma.

Objective: Scleroderma-associated autoantibodies (SSc-Abs) are specific in participants (pts) with systemic sclerosis and are associated with organ involvement. Our objective was to assess the influence of baseline SSc-Abs on the trajectories of the clinical outcome assessments (COAs) in a phase III randomized controlled trial.

Methods: We used data on both the groups who received placebo (Pbo) and tocilizumab from the focuSSced trial. The SSc-Ab panel was assessed centrally. We analyzed four groups with SSc-Abs: anti-topoisomerase 1 antibody (ATA), anti-RNA polymerase 3 antibody (RNAP3), anti-centromere antibody, and negative for all three (triple negative). We assessed the impact of baseline SSc-Abs on six COAs: modified Rodnan skin score (mRSS), forced vital capacity (FVC%), Health Assessment Questionnaire Disability Index, patient and clinical global assessments, and American College of Rheumatology (ACR) Composite Response Index in Systemic Sclerosis (CRISS).

Results: We observed that all COAs, except for FVC%, improved for the group who received Pbo during the 48-week period. For mRSS, pts with RNAP3 showed the largest Pbo effect (7.20 per year, n = 14) and smallest for ATA (3.28 per year, n = 49). This trend was also seen for the ACR CRISS (0.00-1.00 scale), with median improvement at week 48 of 0.94 for RNAP3 versus 0.01 for ATA. ATA enriched for FVC% decline of 7.34% per year versus 2.54% per year for RNAP3. In the group who received tocilizumab, similar changes were seen in the mRSS and ACR CRISS with preservation of lung function, irrespective of SSc-Ab type.

Conclusion: Our result shows a differential effect of SSc-Abs on the trajectories of COAs over 48 weeks in group who received Pbo. These findings highlight the importance of incorporating SSc-Abs in trial design, either as a stratification factor or limiting the SSc-Abs that are included in the trials.