Disease-Modifying Antirheumatic Drugs for Hand Osteoarthritis: A Systematic Review and Network Meta-analysis

To compare the symptomatic efficacy, safety, and exploratory structural evidence of disease-modifying antirheumatic drug therapies in patients with hand osteoarthritis, with particular attention to inflammatory and erosive phenotypes.

We searched PubMed, Web of Science, Embase, the Cochrane Library, ClinicalTrials.gov, and the Chinese Clinical Trial Registry from inception to 12 March 2026 for randomized controlled trials evaluating disease-modifying antirheumatic drug therapies in hand osteoarthritis. Eligible trials included patients with general, inflammatory, erosive, or thumb-base hand osteoarthritis, while studies involving rheumatoid arthritis or other inflammatory arthritides were excluded. Interventions were classified as conventional synthetic or biologic disease-modifying antirheumatic drugs. Pain intensity and hand function were considered primary clinical outcomes. Inflammatory symptom-related outcomes, including swollen and painful joint counts and stiffness, were analysed separately. Treatment-emergent adverse events and serious adverse events were primary safety outcomes, while imaging and biomarker outcomes were treated as exploratory evidence related to potential structural disease modification. A frequentist network meta-analysis was performed. Continuous outcomes were summarized as standardized mean differences and dichotomous outcomes as odds ratios, both with 95% confidence intervals.

Twelve randomized controlled trials involving 1317 participants and seven active disease-modifying antirheumatic drug therapies were included. Methotrexate and hydroxychloroquine were classified as conventional synthetic disease-modifying antirheumatic drugs, whereas adalimumab, etanercept, tocilizumab, lutikizumab, and otilimab were classified as biologic disease-modifying antirheumatic drugs. No eligible trial of a targeted synthetic disease-modifying antirheumatic drug was identified. For pain intensity outcomes, etanercept and tocilizumab were associated with lower long-term visual analogue scale pain than placebo, whereas no intervention showed consistent improvement in hand function. For inflammatory symptom-related outcomes, tocilizumab showed a short-term reduction in painful and swollen joint counts, and adalimumab reduced swollen joint counts in some analyses. However, these findings were outcome-specific, time-dependent, and largely based on sparse, placebo-centred networks. No clear differences were detected in overall treatment-emergent adverse events or serious adverse events, but safety evidence was limited by small sample sizes, short exposure durations, and inconsistent adverse-event reporting. Imaging and biomarker outcomes were heterogeneous and insufficient for quantitative synthesis across most endpoints.

Current randomized evidence does not support the routine use of disease-modifying antirheumatic drugs for hand osteoarthritis. Selected biologic agents showed limited symptomatic signals, particularly in pain or inflammatory joint outcomes, but these findings should not be interpreted as evidence of disease modification. Structural and biomarker evidence remains exploratory and insufficient. Future trials should focus on phenotype-enriched hand osteoarthritis populations and use standardized clinical, imaging, biomarker, and safety outcomes.

Level I, therapeutic studies.

PROSPERO CRD420261353132.