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...
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| Language: | English |
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Wiley
2025-01-01
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| Series: | ACR Open Rheumatology |
| Online Access: | https://doi.org/10.1002/acr2.11782 |
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| author | Basmah Al Dulaijan Suiyuan Huang Celia J. F. Lin Christopher P. Denton Dinesh Khanna |
| author_facet | Basmah Al Dulaijan Suiyuan Huang Celia J. F. Lin Christopher P. Denton Dinesh Khanna |
| author_sort | Basmah Al Dulaijan |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-9f1e3a36fc4945eb8d676e3517bd5338 |
| institution | Kabale University |
| issn | 2578-5745 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | ACR Open Rheumatology |
| spelling | doaj-art-9f1e3a36fc4945eb8d676e3517bd53382025-02-04T06:21:23ZengWileyACR Open Rheumatology2578-57452025-01-0171n/an/a10.1002/acr2.11782Impact of Scleroderma‐Associated Autoantibodies on Clinical Outcome Assessments: Post Hoc Analysis From a Randomised, Double‐blind, Placebo‐controlled, Phase 3 Trial of Tocilizumab in SclerodermaBasmah Al Dulaijan0Suiyuan Huang1Celia J. F. Lin2Christopher P. Denton3Dinesh Khanna4University of Michigan Ann ArborUniversity of Michigan Ann ArborGenentech San Francisco CaliforniaRoyal Free Hospital and University College London London United KingdomUniversity of Michigan Ann ArborObjective 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.https://doi.org/10.1002/acr2.11782 |
| spellingShingle | Basmah Al Dulaijan Suiyuan Huang Celia J. F. Lin Christopher P. Denton Dinesh Khanna 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 ACR Open Rheumatology |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| url | https://doi.org/10.1002/acr2.11782 |
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