Muscle relaxant use and the associated risk of Sjögren’s syndrome and dry eye disease (including keratoconjunctivitis sicca) in patients with ankylosing spondylitis: a population-based cohort study

Background: Muscle relaxants are widely used for the treatment of ankylosing spondylitis (AS) and inevitably have many adverse reactions. Individuals with AS frequently present with ocular symptoms. However, the association of muscle relaxants with the increase of dry eye or Sjogren’s syndrome (SS) in AS patients remains unclear. Objectives: To investigate the association between muscle relaxant use and the risks of Sjögren’s syndrome and dry eye disease (including keratoconjunctivitis sicca) in patients with AS. Design: A population-based retrospective cohort study. Methods: This population-based retrospective cohort study identified patients suffering from AS between 2007 and 2017 ( N = 26,806,963) in the National Health Insurance Research Database (NHIRD) of Taiwan. The demographic data of two study groups, namely muscle relaxant users and non-users, were collected in the present study. The inverse probability of treatment weighting (IPTW) was used to balance the clinical confounders. Furthermore, we used Kaplan–Meier analyses and Cox proportional hazard regression to analyze the association between cumulative muscle relaxant use and SS or dry eye risk in AS patients. Results: After exclusion, 68,970 muscle relaxant users and 31,863 non-users were included in our study. The risks of composite outcome (hazard ratios (HR) 1.37 (1.31–1.43), aHR1.18 (1.13–1.24), and IPTW HR 1.17 (1.13–1.22)), Sjogren’s syndrome (HR 1.63 (1.47–1.79), aHR 1.44 (1.30–1.59), and IPTW HR 1.45 (1.32–1.59)), Dry eye disease (including keratoconjunctivitis sicca) (HR 1.32 (1.26–1.39), aHR 1.12 (1.06–1.17), and IPTW HR 1.11 (1.06–1.16)) were all significantly higher among muscle relaxant users ( p < 0.0001). Moreover, higher doses of muscle relaxant use increased higher risks of composite outcome (25< medication possession ratio (MPR), aHR = 1.77 (1.60–1.96)) and dry eye disease (25< MPR, aHR = 1.74 (1.56–1.94)) ( p < 0.0001 for trend). However, there was higher risk of Sjogren’s syndrome among the patients who received 5< MPR ⩽10 (aHR = 1.70 (1.49–1.93)). Muscle relaxant users who received ethers chemically related to antihistamines and oral muscle relaxant users had higher risks of composite outcome, Sjogren’s syndrome, and dry eye disease. Conclusion: This study demonstrates that cumulative muscle relaxant exposure might increase the risk of dry eye or even SS at a dose-dependent manner.