Individualizing NSAID therapy in axial spondyloarthritis: N-of-1 trials with Bayesian analysis.

OBJECTIVE

Axial spondyloarthritis (axSpA) is a chronic inflammatory disease predominantly affecting the spine and sacroiliac joints. NSAIDs are first-line therapy, but individual responses vary widely. We evaluated the efficacy and patient preference of three NSAIDs (celecoxib, meloxicam and naproxen) through Bayesian N-of-1 clinical trials to optimize axSpA management.

METHODS

We conducted N-of-1 trials with 42 patients meeting ASAS criteria for axSpA. Each patient was asked to complete two cycles of randomized double-blind crossover comparisons of the three NSAIDs, each for 4 weeks. The primary end point was the change in the Ankylosing Spondylitis Disease Activity Score (ASDAS). Bayesian analysis assessed the average treatment effect of each NSAID based on individual patient responses.

RESULTS

Thirty patients completed the trial series. All three NSAIDs resulted in reductions in ASDAS overall across all individuals (posterior probability of benefit [PPB] >0.99 of >0 reduction). No single NSAID demonstrated superiority across all patients. Patient preferences varied, with individualized responses to NSAID therapy identified through Bayesian analysis. The preferred NSAID for each patient showed a larger reduction in ASDAS compared with the least effective NSAID (0.88 vs 0.12, PPB >0.99), with potential clinically important improvement (PPB [0.6] = 0.96).

CONCLUSIONS

Applying N-of-1 trials and Bayesian analysis effectively optimized NSAID therapy for axSpA in terms of efficacy and accounting for side effect profile. This approach raises the possibility of more efficient systemic individualization than usual care.

TRIAL REGISTRATION: ClinicalTrials.gov NCT04115098.