The Evolving Landscape of Outcome Measures in Myositis Clinical Trials: A Systematic Review

Disease heterogeneity with several myositis subtypes and manifestations complicates trial design, particularly the selection of outcome measures that adequately capture disease activity, treatment response, and patient experience across subtypes. Our goal was to characterize the evolving landscape of outcome measures, including patient reported outcome measures (PROMs), used in myositis randomized controlled trials (RCTs), and to identify gaps in current outcome measure selection.

A systematic literature review was conducted across PubMed, EMBASE, CINAHL Complete, Europe PMC, ClinicalTrials. gov, and the International Clinical Trials Registry Platform. Pharmacologic phase 2 to 4 myositis RCTs published between 01/2010 and 12/2023 enrolling adults were included. Two reviewers independently screened records and extracted trial characteristics, primary and secondary endpoints, and PROMs.

Nineteen RCTs met the inclusion criteria, including 1,221 participants (mean age 56 years, 66.4% female) with dermatomyositis/polymyositis (48%), inclusion body myositis (36.4%), and immune-mediated necrotizing myopathy (2%). Earlier trials relied on manual muscle testing, creatine kinase (CK) levels, and the International Myositis Assessment and Clinical Studies Group Definition of Improvement (DOI) as primary endpoints, which were replaced by the Total Improvement Score by 2022 to 2023, but variability in its use was noted. PROM use was sparse before 2019 but increased thereafter. The most commonly used PROMs included the Health Assessment Questionnaire, Patient Global Disease Activity, and SF-36.

Endpoints in myositis trials shifted from heavy reliance on muscle-specific measures to composite multisystem indices. Key gaps are noted in PROM use, including underutilization of PROMs on fatigue and pain. Future trials should prioritize including validated, myositis-appropriate, and patient-centered outcome measures.