Schieker, M, Conaghan, PG orcid.org/0000-0002-3478-5665, Mindeholm, L et al. (7 more authors) (2020) Effects of Interleukin-1β Inhibition on Incident Hip and Knee Replacement: Exploratory analyses from a randomized, double-blind, placebo-controlled trial. Annals of Internal Medicine, 173 (7). pp. 509-515. ISSN 0003-4819
Abstract
Background: Osteoarthritis is a common inflammatory disorder with no disease-modifying therapies. Whether inhibition of interleukin-1β (IL-1β) can reduce the consequences of large joint osteoarthritis is unclear.
Objective: To determine whether IL-1β inhibition with canakinumab reduces incident total hip or knee replacement (THR/TKR).
Design: Exploratory analysis of a randomized trial. (ClinicalTrials.gov: NCT01327846)
Setting: 1091 clinical sites in 39 countries.
Participants: 10 061 CANTOS (Canakinumab Anti-inflammatory Thrombosis Outcomes Study) participants.
Intervention: Random allocation to placebo or canakinumab (50, 150, or 300 mg) subcutaneously once every 3 months.
Measurements: The primary and secondary outcomes were time to first incident THR/TKR and time to first occurrence of an osteoarthritis-related adverse event (AE). Data were obtained through blinded ascertainment of trial clinical and safety databases.
Results: Median follow-up was 3.7 years. For the individual canakinumab dose groups, compared with placebo, hazard ratios (HRs) for incident THR/TKR during follow-up were 0.60 (95% CI, 0.38 to 0.95) for the 50-mg group, 0.53 (CI, 0.33 to 0.84) for the 150-mg group, and 0.60 (CI, 0.38 to 0.93) for the 300-mg group. Thus, in the pooled canakinumab groups, compared with the placebo group, incidence rates for THR/TKR were 0.31 and 0.54 events per 100 person-years (HR, 0.58 [CI, 0.42 to 0.80]; P = 0.001), respectively. The HR for the secondary end point of osteoarthritis-related AEs was 0.73 (CI, 0.61 to 0.87). Similar findings were observed in analyses restricted to participants with a history of osteoarthritis.
Limitation: Because the parent trial was not designed to examine the efficacy of IL-1β inhibitors in osteoarthritis, information on structural joint outcomes was not collected.
Conclusion: Findings from this exploratory analysis of a randomized controlled trial support further investigation of IL-1β inhibition for treatment of large joint osteoarthritis.
Primary Funding Source: Novartis Pharmaceuticals.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2020 American College of Physicians. All Rights Reserved. This is an author produced version of an article published in Annals of Internal Medicine. Reproduced with permission from the publisher. |
Keywords: | Arthroplasty; Lung and intrathoracic tumors; Cartilage; Adverse events; Rheumatoid arthritis; Total hip replacement; Gout; Osteoarthritis; Joint replacement surgery; Knees |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Institute of Rheumatology & Musculoskeletal Medicine (LIRMM) (Leeds) > Musculoskeletal Medicine & Imaging (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 29 Jul 2020 13:40 |
Last Modified: | 25 Jun 2023 22:22 |
Status: | Published |
Publisher: | American College of Physicians |
Identification Number: | 10.7326/M20-0527 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:163825 |