Long-term non-steroidal anti-inflammatory drug therapy in axial spondyloarthritis: a systematic review and meta-analysis of clinical, radiographic, and safety outcomes

Objective: To evaluate the efficacy of prolonged (≥6 months) non-steroidal anti-inflammatory drug (NSAID) therapy in axial spondyloarthritis (axSpA).Methods: Following PRISMA guidelines and PROSPERO registration (CRD420251038493), six database were searched through April 2025.Eligible studies reported reporting Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS), and safety.Random-effects meta-analyses synthesized mean differences (MDs) and risk ratios (RRs).Results: Twenty-three studies (n=4,791) were included.Long-term NSAID therapy was associated with modest trend toward improvements in disease activity (BASDAI MD -0.80; 95% confidence interval [CI] -1.51 to -0.08) and function (BASFI MD -0.66; 95% CI -1.44 to 0.13), though with substantial heterogeneity.The limited available evidence does not support a consistent effect of long-term NSAID use on radiographic progression (ΔmSASSS MD -1.08; 95% CI -3.66 to 1.50).Safety analyses showed no overall excess of adverse events with non-selective NSAIDs (RR 1.16; 95% CI 0.84 to 1.61), while gastrointestinal risks were increased (RR 2.23; 95% CI 1.32 to 3.77) and cardiovascular outcomes remained imprecise (RR 1.10; 95% CI 0.39 to 3.12).Subgroup analyses indicated greater clinical benefit from cyclooxygenase-2-selective agents.Conclusion: Prolonged NSAID therapy in axSpA may contribute to symptom control and remains an important treatment option.Careful monitoring is warranted for gastrointestinal and cardiovascular safety, and individualized decision-making is essential.Future trials with standardized exposure metrics and real-world evidence are needed to clarify long-term benefits across patient subgroups.