Does osteoarthritis modify the association between NSAID use and risk of comorbidities and adverse events?

Objectives: To investigate the role of osteoarthritis (OA) in the incidence of musculoskeletal, metabolic, cardiovascular, digestive, neuro-psychological, kidney and other comorbidities/adverse events after (i) incident non-steroidal anti-inflammatory drug (NSAID) initiation and (ii) NSAID discontinuation. Methods: We used register data for the population of Skåne, Sweden. For (i), we analysed the association between starting NSAIDs and the risk of incident outcome events in the 6 years following NSAID dispensation among people with prevalent OA vs no OA. For (ii) we studied the effect of discontinuing NSAIDs among people with and without OA up to 120 days. We used flexible parametric models to estimate adjusted differences in cumulative incidence with NSAIDs as time-varying exposure in the presence of non-proportional hazards. Results: For (i) we included between 243,832 and 409,749 persons. In the whole cohort, over the 6 years of follow-up, NSAID initiation was associated with a 3% (metabolic) to 16% (musculoskeletal) higher cumulative incidence of outcomes compared to non-users. The difference between those initiating NSAIDs vs non-users was similar in those with and without OA for most outcomes, but in those with OA the increase was lower for neuro-psychological (95%CI: 3.7%-4.6% vs 7.1%-7.9%) and musculoskeletal comorbidities (12%-14.5% vs 16.2%-17.2%).In (ii), we found no interaction between OA and NSAID discontinuation. NSAID discontinuation was associated with decreased risks for most of the outcomes, from -1.3% for musculoskeletal to -0.4% for cardiovascular comorbidities. Conclusions: OA appears to have little influence on the increased risk of comorbidities observed after NSAID initiation or decrease after discontinuation.