Risk of musculoskeletal disorders associated with Bruton’s tyrosine kinase inhibitors: a disproportionality analysis of FAERS database and meta-analysis

Randomized controlled trials (RCTs) have reported an increased risk of musculoskeletal disorders with BTK inhibitors (BTKis). We conducted a disproportionality analysis using the FDA Adverse Event Reporting System (FAERS) and a meta-analysis of RCTs to further investigate. A retrospective case/non-case study was performed using FAERS reports through Q2 2024. Disproportionality analysis calculated Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), and Information Component (IC) to identify signals (PRR ≥2, lower bound ROR > 1, IC₀₂₅ > 0). A meta-analysis calculated risk ratios (RR) for musculoskeletal outcomes. In FAERS, ibrutinib was associated with increased reports of muscle spasms [PRR: 2.2 (χ² : 521.9), LB ROR: 2.1, IC₀₂₅ = 1.0]. Acalabrutinib showed higher risks for myalgia [PRR: 2.4, LB ROR: 2.0, IC₀₂₅ = 0.9] and bone pain [PRR: 2.2, LB ROR: 1.6, IC₀₂₅ = 0.6]. In the meta-analysis, ibrutinib was associated with higher risks of arthralgia (RR: 1.46, 95% CI 1.21–1.76), muscle spasm (RR: 2.32, 95% CI 1.72–3.12), and back pain (RR: 1.22, 95% CI 0.75–1.96). Findings from FAERS and meta-analysis suggest a stronger association between BTKis, particularly ibrutinib, and musculoskeletal adverse events.