Brom, Martin, Saxer, Franziska, Mindeholm, Linda, Schieker, Matthias and Philip, Conaghan (2025) Is It Time to Revisit the Role of Interleukin-1 Inhibitors in Osteoarthritis? Diabetes, metabolic syndrome and obesity : targets and therapy, 18. pp. 1753-1764. ISSN 1178-7007

Abstract

There remains a huge unmet need for new osteoarthritis (OA) therapies. A putative reason for the failure of some therapies has been the absence of well-defined phenotypes, which might be more appropriate for specific targeted treatment. Interleukin-1 (IL-1) plays a key role in the development of OA, but the results of clinical trials targeting IL-1 in OA have to date been disappointing.This narrative review is based on a literature search for publications describing interventions with direct Il-1 pathway inhibitors in patients with knee OA and substantiated by a description of key pre-clinical observations.Randomized controlled studies using IL-1 inhibition as treatment approach to knee OA have read out negatively, although trends for an improvement in pain and impact on biomarkers could be observed. However, in a post-hoc analysis of the large CANTOS trial data (Canakinumab Anti-inflammatory Thrombosis Outcomes Study) testing an anti-IL-1 monoclonal antibody for the secondary prevention of cardiovascular events treatment arms receiving canakinumab demonstrated a substantial reduction in the incidence rate of joint replacement compared to those receiving placebo. Similar results have been reported from a post-hoc analysis of another cardiovascular risk reduction study, the low-dose colchicine 2 (LoDoCo 2) trial, raising the possibility of a beneficial effect of IL-1 inhibition in the subset of patients with metabolic phenotype.Based on the above results, it seems timely to revisit the role of IL-1 in OA, its relationship with chronic low-grade inflammation and its relevance in the subset of metabolic OA.

Item Type:	Article
Date Deposited:	18 Jul 2025 00:45
Last Modified:	18 Jul 2025 00:45
URI:	https://oak.novartis.com/id/eprint/54597