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New composite endpoint in early diffuse cutaneous systemic sclerosis: revisiting the provisional American College of Rheumatology Composite Response Index in Systemic Sclerosis
  1. Dinesh Khanna1,
  2. Suiyuan Huang1,2,
  3. Celia J F Lin3,
  4. Cathie Spino2
  1. 1Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
  2. 2Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, Michigan, USA
  3. 3Genentech Inc, South San Francisco, California, USA
  1. Correspondence to Dr Dinesh Khanna, Division of Rheumatology, University of Michigan, Ann Arbor, MI 48109, USA; khannad{at}med.umich.edu

Abstract

Objectives American College of Rheumatology Composite Response Index in Systemic Sclerosis (ACR-CRISS) is a composite endpoint to assess the likelihood of improvement in diffuse systemic sclerosis. ACR-CRISS is a weighted score and includes five core set measures: modified Rodnan skin score, FVC% predicted, health assessment questionnaire–disability index, and patient and clinician global assessments.

Methods We analysed core set measures from 354 participants who participated in three placebo-controlled trials. We generated 10 development datasets, randomly selected from 2/3 of the participants, stratified by study and treatment group. The remaining participants (1/3 of the participants) formed the validation sets. Risk differences (RDs) between active and placebo treatments were calculated by averaging over the replicate datasets; bootstrap 95% CIs for the RDs to estimate the magnitude of treatment effects.

Results In the development sets (n=237), the proportion of participants in the active group had statistically higher improvement in >1 of 5 core set measures versus the placebo group. For example, the proportion who improved by ≥20% in ≥3 core set measures was 49.4% in the active versus338.9% in the placebo; RD: 10.5%, 95% CI4.9 % to 16.1%. In the validation sets (n=117), the proportion who improved by ≥20% in ≥3 core set measures was 50.3% in the active versus35.63% in the placebo (RD:114.8%, 95% CI 3.1% to225.7%). Similar trends were seen with larger percentage cut-offs.

Conclusion Revised CRISS, as assessed by the proportion of participants who improved by a certain percentage in ≥3 of 5 core set measures, is a potential new composite outcome measure.

  • scleroderma
  • systemic
  • outcome assessment
  • health care
  • patient reported outcome measures
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Footnotes

  • Handling editor Josef S Smolen

  • Contributors All listed authors provided substantial contributions to the conception or design of the work; or the acquisition, analysis or interpretation of data for the work; drafted the work or revised it critically for important intellectual content; had final approval of the version to be published; and have agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

  • Funding DK's work was supported by the NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases (K24-AR-063120 and 1R01-AR070470-01A1).

  • Competing interests DK reports grants from NIH/NIAMS, grants from Immune Tolerance Network, grants and personal fees from Bayer, grants from Bristol Myers Squibb, grants from Horizon, grants from Pfizer, personal fees from Acceleron, personal fees from Acetlion, personal fees from Amgen, personal fees from Blade Therapeutics, personal fees from Boehringer Ingelheim, personal fees from CSL Behring, personal fees from Corbus, personal fees from Cytori, personal fees from Galapagos, personal fees from Genentech/Roche, personal fees from GSK, personal fees from Horizon, personal fees from Merck, personal fees from Mitsubishi Tanabe Pharma, personal fees from Regeneron, personal fees from Sanofi-Aventis, personal fees from United Therapeutics, other from Impact PH, personal fees from Eicos Sciences, and personal fees and other from CiviBioPharma/Eicos Sciences outside the submitted work. SH has nothing to report. CJFL reports other from Genentech during the conduct of the study; other from Genentech outside the submitted work and owns stock in Roche. CS reports statistical consulting from Eicos Sciences outside the submitted work.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available on reasonable request.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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