Pos0374 Glucosamine and Cancer Incidence in Patients With Osteoarthritis: Real-World Observational Study

Background: The widespread use of glucosamine to treat joint pain and osteoarthritis is controversial, with conflicting findings of its effectiveness in randomized trials and their meta-analyses, as well as historical disagreement among some treatment guidelines.[1-3] On the other hand, several large observational studies have associated glucosamine use with significant reductions in major outcomes, including cancer incidence, cardiovascular events, and mortality. These studies were shown to be potentially affected by selection bias resulting from using cohorts not based on new users of glucosamine.[4] Nonetheless, even if current guidelines now deem glucosamine to be ineffective to treat osteoarthritis and joint pain, these observational studies continue to be published and give support to indirect benefits of glucosamine on reducing the risk of cancer and other major outcomes. Objectives: To assess whether glucosamine use is associated with reductions in cancer incidence in patients with osteoarthritis in a real-world setting, using an observational new-user study design that emulates a randomized trial and avoids selection bias. Methods: The subjects were identified from the United Kingdom's Clinical Practice Research Datalink (CPRD), a primary care database of medical records for over 50 million people from more than 1800 general practices. The base cohort included all patients with a diagnosis of osteoarthritis, 30 years of age or more in 1995-2017. The prevalent new-user cohort design, that emulates a randomized trial, was used to time-match each patient initiating glucosamine with a non-user on the timing of glucosamine initiation and on time-conditional propensity scores. Subjects were followed until cancer incidence. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) of incidence of any cancer, as well as lung, colorectal, breast and prostate cancers, comparing glucosamine use with non-use. Results: The study cohort included 20,620 new-users of glucosamine who were time- and propensity score-matched to 20,620 non-users identified among the base cohort of patients with osteoarthritis. Glucosamine use was initiated an average two years after the diagnosis of osteoarthritis. At cohort entry, the subjects were 67 years of age and 67% were female. During the one-year baseline period, 30% were using aspirin, 50% NSAIDS and 60% an opioid. Over an average follow-up of 8 years, the overall rate of any cancer incidence was 1.48 per 100 per year. The HR of any cancer incidence with glucosamine use was 0.98 (95% CI 0.93-1.04), compared with non-use. For lung cancer, the HR with glucosamine use was 0.99 (95% CI 0.82-1.19), while it was 1.14 (95% CI 0.95-1.37) for colorectal cancer, 1.09 (95% CI 0.93-1.27) for breast cancer in women and 1.07 (95% CI 0.91-1.27) for prostate cancer. Conclusion: In this large, real-world cohort study of patients with osteoarthritis, designed to emulate a randomized trial, treatment with glucosamine did not reduce the incidence of any cancer, nor the incidence of lung, colorectal, breast and prostate cancers. Our observational study confirms that the previous observational studies reporting significant reductions in cancer incidence with glucosamine were affected by selection bias, resulting from not assessing glucosamine users at the time of initiation. Our study, designed to avoid this selection bias, does not support the use of glucosamine to prevent cancer in patients with osteoarthritis. REFERENCES: [1] Cutolo M, Berenbaum F, Hochberg M, Punzi L, Reginster JY. Commentary on recent therapeutic guidelines for osteoarthritis. Semin Arthritis Rheum. 2015;44(6):611-617. [2] Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update. Arthritis & Rheumatism. 2000;43(9):1905-1915. [3] Arden NK, Perry TA, Bannuru RR, et al. Non-surgical management of knee osteoarthritis: comparison of ESCEO and OARSI 2019 guidelines. Nat Rev Rheumatol. 2021;17(1):59-66. [4] Suissa K, Hudson M, Suissa S. Glucosamine and lower mortality and cancer incidence: Selection bias in the observational studies. Pharmacoepidemiol Drug Saf. 2022;31(12):1272-1279. Acknowledgements: NIL. Disclosure of Interests: Samy Suissa Boehringer-Ingelheim, Novartis, Merck, Pfizer, Seqirus – Consulting AstraZeneca, Atara, Bristol-Myers-Squibb, Novartis, Panalgo - Advisory Board Member, Eros Comin: None declared, Karine Suissa: None declared, Marie Hudson UCB, Pfizer, AstraZeneca, Boehringer Ingelheim, Merck, Boehringer Ingelheim, Bristol Myers-Squibb, Boehringer Ingelheim.