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Worth, Claudia, Al-Mossawi, M. Hussein, Macdonald, Joanne, Fisher, Benjamin A., Chan, Antoni, Sengupta, Raj, Packham, Jonathan, Gaffney, Karl 
ORCID: https://orcid.org/0000-0002-7863-9176, Gullick, Nicola, Cook, Jonathan A., Corn, Tim H., Teh, James, Machado, Pedro M., Taylor, Peter C. and Bowness, Paul
(2024)
Granulocyte-macrophage colony-stimulating factor neutralisation in patients with axial spondyloarthritis in the UK (NAMASTE):a randomised, double-blind, placebo-controlled, phase 2 trial.
The Lancet Rheumatology, 6 (8).
e537-e545.
ISSN 2665-9913
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Abstract
Background: Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a proinflammatory cytokine overproduced in several inflammatory and autoimmune diseases, including axial spondyloarthritis. Namilumab is a human IgG1 monoclonal anti-GM-CSF antibody that potently neutralises human GM-CSF. We aimed to assess the efficacy of namilumab in participants with moderate-to-severe active axial spondyloarthritis. Methods: This proof-of-concept, randomised, double-blind, placebo-controlled, phase 2, Bayesian (NAMASTE) trial was done at nine hospitals in the UK. Participants aged 18–75 years with axial spondyloarthritis, meeting the Assessment in SpondyloArthritis international Society (ASAS) criteria and the ASAS-defined MRI criteria, with active disease as defined by a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), were eligible. Those who had inadequately responded or had intolerance to previous treatment with an anti-TNF agent were included. Participants were randomly assigned (6:1) to receive subcutaneous namilumab 150 mg or placebo at weeks 0, 2, 6, and 10. Participants, site staff (except pharmacy staff), and central study staff were masked to treatment assignment. The primary endpoint was the proportion of participants who had an ASAS ≥20% improvement (ASAS20) clinical response at week 12 in the full analysis set (all randomly assigned participants). This trial is registered with ClinicalTrials.gov (NCT03622658). Findings: From Sept 6, 2018, to July 25, 2019, 60 patients with moderate-to-severe active axial spondyloarthritis were assessed for eligibility and 42 were randomly assigned to receive namilumab (n=36) or placebo (n=six). The mean age of participants was 39·5 years (SD 13·3), 17 were women, 25 were men, 39 were White, and seven had previously received anti-TNF therapy. The primary endpoint was not met. At week 12, the proportion of patients who had an ASAS20 clinical response was lower in the namilumab group (14 of 36) than in the placebo group (three of six; estimated between-group difference 6·8%). The Bayesian posterior probability η was 0·72 (>0·927 suggests high clinical significance). The rates of any treatment-emergent adverse events in the namilumab group were similar to those in the placebo group (31 vs five). Interpretation: Namilumab did not show efficacy compared with placebo in patients with active axial spondyloarthritis, but the treatment was generally well tolerated. Funding: Izana Bioscience, NIHR Oxford Biomedical Research Centre (BRC), NIHR Birmingham BRC, and Clinical Research Facility.
| Item Type: | Article |
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| Additional Information: | Funding Information: This study was funded by Izana Bioscience (including salary funding to CW; number 10791466), NIHR Oxford BRC (received by PCT and PB), and NIHR Birmingham BRC and Clinical Research Facility (received by BAF). We thank the patients for their participation. We also thank Walter Maksymowych and Joel Paschke for giving access to the CARE Arthritis web-based imaging scoring platform and Subash Muniswamaiah (IQVIA, Reading, UK) for providing statistical advice and reviewing the manuscript. We thank The British Society for Spondyloarthritis for assistance with patient recruitment. The views expressed are those of the authors and not necessarily those of the National Health Service, NIHR, or the UK Department of Health. Publisher Copyright: © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license |
| Uncontrolled Keywords: | rheumatology,immunology and allergy,immunology,sdg 3 - good health and well-being ,/dk/atira/pure/subjectarea/asjc/2700/2745 |
| Faculty \ School: | Faculty of Medicine and Health Sciences > Norwich Medical School |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 03 Sep 2024 16:32 |
| Last Modified: | 25 Sep 2024 18:04 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/96488 |
| DOI: | 10.1016/S2665-9913(24)00099-7 |
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