Are NSAIDs Associated with Increased Risk of Developing Psoriatic Arthritis?

Several studies have indicated that initiating treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with worsening psoriasis symptoms. There is also evidence that the use of nonaspirin NSAIDs is associated with an increased risk of Crohn’s disease and ulcerative colitis (which themselves have been shown to be associated with psoriasis and psoriatic arthritis).

Because of the “genetic and pathologic connections between psoriasis and Crohn’s disease,” the authors of “Use of Aspirin, Nonsteroidal Anti-inflammatory Drugs, and Acetaminophen (Paracetamol), and Risk of Psoriasis and Psoriatic Arthritis: A Cohort Study,” published in Acta Dermato-Venereologica, evaluated a potential link between the use of aspirin, nonaspirin NSAIDs, and acetaminophen and risk of psoriatic arthritis and psoriasis.

Using data from the Nurses’ Health Study II (NHS II), the authors screened participants (N=95540) for regular aspirin (including low-dose aspirin), NSAID, and acetaminophen use, categorizing medication use according to regular use status, duration, and weekly dose. They used “Cox proportional hazards analyses stratified by age and 2-year follow-up intervals to estimate the age- and multivariate-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between medication use and risk of psoriasis and PsA.”

During 1,321,280 person-years of follow-up from 1991 to 2005, the authors documented 646 incident psoriasis cases and 165 concomitant PsA cases.

Analysis of data showed that regular use of acetaminophen was associated with a higher risk of developing psoriasis or psoriasis with concomitant PsA. However, only the hazard ratios of PsA associated with regular acetaminophen use “remained significant in fully-adjusted models accounting for aspirin and other NSAIDs.” Regular NSAIDs users were also more likely to develop psoriasis or PsA compared to nonregular users. The authors found no clear association between regular aspirin use and disease risk.

Longer duration of NSAID and acetaminophen use was also associated with higher disease risk, especially for PsA. The authors reported that, compared to women who reported no use, “regular acetaminophen users with use duration of 1—6 years, 7–10 years, and more than 10 years had fully-adjusted HRs of 1.77 (95% CI: 1.19–2.62), 1.66 (95% CI: 0.91–3.02), and 3.60 (95% CI: 2.02–6.41) respectively for PsA, and regular NSAIDs users with use duration of 1–6 years, 7–10 years, and more than 10 years had fully-adjusted HRs of 1.51 (95% CI: 0.98–2.33), 2.09 (95% CI: 1.22–3.58), and 2.10 (95% CI: 1.11–3.96) respectively for PsA.”

When dosage was taken into account, “acetaminophen dosage showed the most robust associations with psoriasis and PsA among the three drugs.”

In their discussion of these results, the authors concluded that their findings “suggest that regular acetaminophen use may be associated with an increased risk of psoriasis and concomitant PsA. In addition, long-term NSAIDs use also appeared to be associated with an increased risk of PsA.” They added that “the biological mechanism linking these drugs and development of psoriasis and concomitant PsA is plausible, and further work is warranted to replicate our findings and to explore the underlying biological evidence.”