Review examines emerging symptomatic and disease-modifying therapies for knee osteoarthritis

A review in Nature Reviews Rheumatology examines emerging treatments for knee osteoarthritis (OA), a heterogeneous whole-joint disease involving biomechanical, metabolic, inflammatory, osteochondral and neurovascular mechanisms. It distinguishes symptom-focused therapies from candidate disease-modifying OA drugs, which have different clinical objectives and regulatory expectations.

The review identifies incretin-based therapies as a promising approach for obesity-associated knee OA and describes semaglutide as the first to show substantial benefits for pain and function. Other symptomatic strategies include extended-release intra-articular glucocorticoids, neurotrophin modulation, methotrexate, lubricating injectables and image-guided neurovascular interventions. Candidate disease-modifying approaches target cartilage anabolism, Wnt signalling, matrix-degrading enzymes, subchondral bone remodelling, immunometabolic pathways and local gene transfer.

Locally administered GLP1 receptor agonists, TPX-100 and intra-articular IL-1 receptor antagonist gene therapy have shown encouraging signals, according to the review. By contrast, mesenchymal stromal cell therapies have demonstrated inconsistent efficacy across phase III trials and no convincing structural benefit.

The authors anticipate greater use of mechanism-based patient selection and combination strategies. However, uncertainties remain about long-term safety and maintenance of incretin-based treatment. The supplied subscription preview provides no sample sizes or numerical treatment effects, limiting assessment of benefit magnitude; symptomatic improvement should not be equated with established disease modification.