Introduction & Objectives
Osteoarthritis (OA) is a major cause of joint pain and disability, affecting roughly 27 million adults in the U.S., and poses a significant economic burden. The knees, hips, hands and spine are most commonly affected, leading to joint deformity and dysfunction. OA is no longer viewed simply as degeneration in the joints, but rather a disease that is driven by low-grade inflammation and complex interactions between genes and the environment. No effective treatments exist to prevent the onset or progression of OA, and novel therapies are needed.
Preclinical models of OA have provided important insights into the pathogenesis of the disease and potential pathways for therapeutic intervention. One such pathway involves adenosine, which is produced endogenously from adenosine triphosphate hydrolysis and serves as an important regulator of inflammation. Extracellular adenosine has been shown to reduce inflammatory responses and ameliorate OA in mouse and rat models. These findings suggest that extracellular adenosine may play an important role in reducing cartilage inflammation and damage, and that it might serve as a therapeutic target for preventing and treating OA in humans.
Ticagrelor and clopidogrel are antiplatelet agents used to treat patients with coronary artery disease. They both work by antagonizing the binding of adenosine diphosphate to the P2Y12 receptor on platelets, thereby reducing platelet aggregation. Ticagrelor was approved by the U.S. Food & Drug Administration in 2011, and clopidogrel was approved in 1997.
Ticagrelor and clopidogrel are both used in patients with coronary artery disease, but only ticagrelor increases extracellular adenosine levels. This study was undertaken to determine whether treatment with ticagrelor is associated with a lower risk of OA.
Methods
Baker et al. conducted a 1:2 propensity score–matched analysis using data from 2011–2017 in the Optum Clinformatics Data Mart. Patients who received either ticagrelor or clopidogrel for 90 days or more were included in the study, and patients with a prior diagnosis of OA or inflammatory arthritis were excluded. OA was identified using International Classification of Diseases codes. The primary outcome was the time to diagnosis of OA after treatment with ticagrelor vs. clopidogrel.
Results
The researchers’ propensity score-matched cohort consisted of 7,007 ticagrelor-treated patients and 14,014 clopidogrel-treated patients, with a median number of days receiving treatment of 287 and 284, respectively. For both groups, the mean age was 64 years, and 73% of the patients were men. Multivariate Cox regression analysis estimated a hazard ratio for developing OA of 0.71 (95% confidence interval 0.64–0.79) (P<0.001) after treatment with ticagrelor compared with clopidogrel.
Conclusion
Treatment with ticagrelor was associated with a 29% lower risk of developing OA than treatment with clopidogrel over five years of follow-up. Baker et al. hypothesize the reduction in OA seen in patients who received ticagrelor may in part be due to increased extracellular adenosine levels.
Refer to the full study for all source material.
Excerpted and adapted from:
Baker MC, Weng Y, Robinson WH, et al. Reduction in osteoarthritis risk after treatment with ticagrelor compared to clopidogrel: A propensity score matching analysis. Arthritis Rheumatol. 2020 Nov;72(11).
