Background: Osteoarthritis (OA) is one of the leading causes of pain and disability worldwide. Despite major efforts, no disease-modifying OA drugs (DMOADs) are available. Drug repurposing offers a low-cost and time-efficient approach to address this unmet need [1]. Although numerous studies in OA patients have used this approach, no review of all these agents exists without restrictions on the original indication, study design, or publication date.

Objectives: This scoping review aims to provide an exhaustive overview of the extent and characteristics of clinical research on authorised drugs investigated for the treatment of OA.

Methods: Electronic database searches were performed from inception till October 2023 in MEDLINE, Embase, and Cochrane using search terms for OA, drugs, and clinical studies. Authorised drugs approved by the Food and Drug Administration (FDA), European Medicines Agency (EMA), or Dutch Medicines Evaluation Board investigated in clinical studies for treating OA were included. Dextrose and drugs indicated for pain (irrespective of aetiology) or OA were excluded. Titles and abstracts were screened by two independent reviewers (MiHe and MeHa) using an AI-based tool and the full text of selected articles was assessed accordingly [2]. Articles were classified according to the investigated drug and categorized based on the targeted endotype. EMA and FDA guidance on DMOADs was used to summarize outcomes according to design and length of follow-up.

Results: From 20464 deduplicated records, 177 articles were included in this review reporting the results of 94 randomized controlled trials (RCTs) including 9 post-hoc analyses, 52 cohorts, 12 case-control studies, 11 cross-sectional studies, 11 pre-post studies, and 4 non-RCTs. At least 42 drugs were identified. Short-term follow-up studies (< 1 year) were predominantly designed as RCTs examining almost exclusively symptom-modifying effects (Table 1). In contrast, long-term follow-up studies (≥ 1 year) used more often existing data and assessed structure-modifying effects as well (Table 2). Overall, significant effects favouring the examined drugs were observed in only a minority of the symptom- and structure-modifying outcomes. The impact on time to OA diagnosis and joint replacement seemed more promising. Drugs examined less than 5 times, including spironolactone, doxycycline, liraglutide, thiazolidinediones, anti-histamines, ticagrelor, β-blockers, coumarins, anti-IL1, anti-IL6, sodium bicarbonate and calcium gluconate, fenofibrate, somatropin, pentosan polysulfate, insulin, N-acetylcysteine, naltrexone, bromelain, fish oil, L-carnitine, folate, vitamin C, and vitamin K showed similar results (data not shown).

Conclusion: Many authorised drugs have already been investigated to be repurposed for the treatment of OA, of which the most extensively investigated mainly targeted the inflammatory and bone endotype. Short-term studies investigated almost exclusively symptom-modifying effects, whereas most long-term studies investigated structure-modifying effects as well. However, long-term studies investigating structural-modifying effects of colchicine, methotrexate, and hydroxychloroquine are lacking. Although no conclusions about the effectiveness could be drawn due to this review’s nature, it provides valuable guidance for future studies involving repurposed drugs.

REFERENCES: [1] Kuswanto W, Baker MC. Repurposing drugs for the treatment of osteoarthritis. DOI: 10.1016/j.joca.2024.05.008

[2] Boetje J, Van De Schoot R. The SAFE Procedure: A Practical Stopping Heuristic for Active Learning-Based Screening in Systematic Reviews and Meta-Analyses. DOI: 10.21203/rs.3.rs-2856011/v1

Acknowledgements: NIL.

Disclosure of Interests: None declared.

© The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.