Fleischmann, RM, Bliddal, H, Blanco, FJ et al. (17 more authors) (2019) A Phase II Trial of Lutikizumab, an Anti–Interleukin‐1α/β Dual Variable Domain Immunoglobulin, in Knee Osteoarthritis Patients With Synovitis. Arthritis & Rheumatology, 71 (7). pp. 1056-1069. ISSN 2326-5191
Abstract
Objective: To assess the efficacy and safety of the anti–interleukin‐1α/β (anti–IL‐1α/β) dual variable domain immunoglobulin lutikizumab (ABT‐981) in patients with knee osteoarthritis (OA) and evidence of synovitis.
Methods: Patients (n = 350; 347 analyzed) with Kellgren/Lawrence grade 2–3 knee OA and synovitis (determined by magnetic resonance imaging [MRI] or ultrasound) were randomized to receive placebo or lutikizumab 25, 100, or 200 mg subcutaneously every 2 weeks for 50 weeks. The coprimary end points were change from baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score at week 16 and change from baseline in MRI‐assessed synovitis at week 26.
Results: The WOMAC pain score at week 16 had improved significantly versus placebo with lutikizumab 100 mg (P = 0.050) but not with the 25 mg or 200 mg doses. Beyond week 16, the WOMAC pain score was reduced in all groups but was not significantly different between lutikizumab‐treated and placebo‐treated patients. Changes from baseline in MRI‐assessed synovitis at week 26 and other key symptom‐ and most structure‐related end points at weeks 26 and 52 were not significantly different between the lutikizumab and placebo groups. Injection site reactions, neutropenia, and discontinuations due to neutropenia were more frequent with lutikizumab versus placebo. Reductions in neutrophil and high‐sensitivity C‐reactive protein levels plateaued with lutikizumab 100 mg, with further reductions not observed with the 200 mg dose. Immunogenic response to lutikizumab did not meaningfully affect systemic lutikizumab concentrations.
Conclusion: The limited improvement in the WOMAC pain score and the lack of synovitis improvement with lutikizumab, together with published results from trials of other IL‐1 inhibitors, suggest that IL‐1 inhibition is not an effective analgesic/antiinflammatory therapy in most patients with knee OA and associated synovitis.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2019, American College of Rheumatology. This is the peer reviewed version of the following article: Fleischmann, RM, Bliddal, H, Blanco, FJ et al. (17 more authors) (2019) A Phase II Trial of Lutikizumab, an Anti–Interleukin‐1α/β Dual Variable Domain Immunoglobulin, in Knee Osteoarthritis Patients With Synovitis. Arthritis & Rheumatology, 71 (7). pp. 1056-1069. ISSN 2326-5191, which has been published in final form at https://doi.org/10.1002/art.40840. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | DMOADs (biologic); knee osteoarthritis; inflammation; cytokines; interleukin-1 |
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: | 08 Jan 2019 12:31 |
Last Modified: | 17 Jan 2020 01:39 |
Status: | Published |
Publisher: | Wiley |
Identification Number: | 10.1002/art.40840 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:140668 |