Composite outcome measures that successfully differentiate active treatments from placebo in psoriatic arthritis trials: a GRAPPA-OMERACT systematic review and network meta-analysis

Objectives: To identify which composite outcome measure most effectively distinguishes active treatments from placebo in randomised controlled trials (RCTs) of biologic or targeted synthetic disease-modifying antirheumatic drugs (b- or tsDMARDs) for psoriatic arthritis (PsA). Methods: A systematic literature review (PROSPERO ID: CRD42024578203) of Cochrane Central Register of Controlled Trials and PubMed identified RCTs comparing b- or tsDMARDs with placebo reporting ≥2 of 7 composite outcome measures shortlisted for evaluation by the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis–Outcome Measures in Rheumatology (GRAPPA-OMERACT) working group (American College of Rheumatology Response Criteria [ACR], Composite Psoriatic Disease Activity Index [CPDAI], Disease Activity index for PSoriatic Arthritis [DAPSA], Minimal Disease Activity [MDA], Psoriatic Arthritis Disease Activity Score [PASDAS], and 3- and 4-Visual Analogue Scale [VAS]). Discriminant capacities were assessed using odds ratio (OR) for binary outcomes, with continuous outcomes converted from standardised mean differences and analysed through network and multivariate meta-analysis techniques. Results: Of 2483 references, 24 trials were included (43 randomised comparisons). CPDAI was rarely reported, and no RCTs reported 3-VAS and 4-VAS. The main network meta-analysis showed differences in discriminant properties for DAPSA vs ACR20 (OR: 0.80; 95% CI: 0.66-0.97; favouring ACR20), DAPSA vs MDA (OR: 0.71; 0.57-0.87; favouring MDA), and PASDAS vs DAPSA (OR: 1.35; 1.10-1.66; favouring PASDAS). Supported by multivariate meta-analysis: MDA (OR: 5.06; 4.20-6.09), ACR20 (OR: 4.01; 3.41-4.73), PASDAS (OR:3.70; 3.00-4.56), DAPSA (OR: 3.02; 2.44-3.75), and CPDAI (OR: 1.86; 0.95-3.64). Sensitivity analyses confirmed a pattern of consistent numerical advantages for MDA and PASDAS. Exploratory analyses showed ACR70 had more discriminant capacity than ACR20 and DAPSA but not ACR50, MDA, and PASDAS. Conclusions: ACR20, MDA, and PASDAS demonstrated greater discriminant capacity than DAPSA. Exploratory analyses suggested greater discriminant capacity for ACR70 compared with ACR20 and DAPSA but not with ACR50, MDA or PASDAS.