EXTENDED REPORT

Minimally important difference in diffuse systemic sclerosis: results from the D-penicillamine study

D Khanna¹, D E Furst², R D Hays^3,5, G S Park^2,4, W K Wong⁴, J R Seibold⁶, M D Mayes⁷, B White^8,*, F F Wigley⁹, M Weisman¹⁰, W Barr¹¹, L Moreland¹², T A Medsger, Jr¹³, V D Steen¹⁴, R W Martin¹⁵, D Collier¹⁶, A Weinstein¹⁴, E V Lally¹⁷, J Varga¹¹, S R Weiner², B Andrews¹⁸, M Abeles¹⁹, P J Clements²

¹ Division of Immunology, Department of Medicine; Institute for the Study of Health, University of Cincinnati, Cincinnati, Ohio, USA; Veterans Affairs Medical Center, Cincinnati
² Department of Medicine, Division of Rheumatology, David Geffen School of Medicine, Los Angeles, California, USA
³ Division of General Internal Medicine and Health Services Research, David Geffen School of Medicine
⁴ Department of Biostatistics, David Geffen School of Medicine
⁵ RAND, Los Angeles
⁶ University of Michigan Scleroderma Program, Ann Arbor, Michigan, USA
⁷ Division of Rheumatology and Clinical Immunogenetics, The University of Texas—Houston Medical School, Houston, Texas, USA
⁸ Department of Rheumatology and Clinical Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USA
⁹ Rheumatology Division, The Johns Hopkins University, Baltimore, Maryland, USA
¹⁰ Division of Rheumatology, Cedars-Sinai Medical Center, Los Angeles
¹¹ Division of Rheumatology, Northwestern University Medical School, Chicago, Illinois, USA
¹² Divison of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, Alabama, USA
¹³ Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
¹⁴ Division of Rheumatology, Georgetown University Medical Center, Washington, DC, USA
¹⁵ Division of Rheumatology, College of Human Medicine, Michigan State University, Grand Rapids, Michigan, USA
¹⁶ Division of Rheumatology, University of Colorado Health Sciences Center, Denver, Colorado, USA
¹⁷ Division of Rheumatology, Brown Medical School, Providence, Rhode Island, USA
¹⁸ Division of Rheumatology, University of California, Irvine, California, USA
¹⁹ Division of Rheumatic Diseases, University of Connecticut Health Center, Farmington, Connecticut, USA

Correspondence to:
D Khanna
Division of Immunology, Department of Medicine, University of Cincinnati, ML 0563, Cincinnati, OH 45267-0563, USA;dinesh.khanna{at}uc.edu

Objective: To estimate minimally important differences (MIDs) in scores for the modified Rodnan Skin Score (mRSS) and Health Assessment Questionnaire—Disability Index (HAQ-DI) in a clinical trial on diffuse systemic sclerosis (SSc).

Participants and methods: 134 people participated in a 2-year, double-blind, randomised clinical trial comparing efficacy of low-dose and high-dose D-penicillamine in diffuse SSc. At 6, 12, 18 and 24 months, the investigator was asked to rate the change in the patient’s health since entering the study: markedly worsened, moderately worsened, slightly worsened, unchanged, slightly improved, moderately improved or markedly improved. Patients who were rated as slightly improved were defined as the minimally changed subgroup and compared with patients rated as moderately or markedly improved.

Results: The MID estimates for the mRSS improvement ranged from 3.2 to 5.3 (0.40–0.66 effect size) and for the HAQ-DI from 0.10 to 0.14 (0.15–0.21 effect size). Patients who were rated to improve more than slightly were found to improve by 6.9–14.2 (0.86–1.77 effect size) on the mRSS and 0.21–0.55 (0.32–0.83 effect size) on the HAQ-DI score.

Conclusion: MID estimates are provided for improvement in the mRSS and HAQ-DI scores, which can help in interpreting clinical trials on patients with SSc and be used for sample size calculation for future clinical trials on diffuse SSc.

Abbreviations: D-Pen, D-penicillamine; HAQ-DI, Health Assessment Questionnaire—Disability Index; HRQOL, health-related quality of life; MID, minimally important difference; mRSS, modified Rodnan Skin Score; SSc, systemic sclerosis

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