Health Sciences
PROMOTE – Placebo-controlled trial of methotrexate to treat painful knee osteoarthritis
We proposed that using methotrexate to treat patients with symptomatic knee osteoarthritis (OA) could be a practical and safe treatment to reduce synovitis and, consequently, pain. Despite a moderate standard effect size, the analgesic effect was of borderline clinical meaningfulness.
Why did we do this research?
Current treatments for OA are severely limited so there is an urgent need for novel treatments to reduce pain. Synovitis is highly prevalent in OA and is associated with pain. Methotrexate is the gold standard treatment for synovitis in other forms of arthritis. We proposed that using methotrexate to treat patients with symptomatic knee OA could be a practical and safe treatment to reduce synovitis and, consequently, pain.
What did we do?
We undertook a pragmatic randomised, double-blind trial of oral methotrexate compared to placebo for the reduction of pain in participants with knee OA. Participants were randomised on a 1:1 basis to methotrexate or placebo, in addition to ongoing usual care, with dose escalation over 8 weeks and a maintenance dose for the remainder of the study. The primary endpoint was average knee pain during the previous week at 6-months. Secondary endpoints included pain, quality-of-life and adverse events.
Who was involved?
Participants with symptomatic (visual analogue scale pain 4/10) and radiographic tibiofemoral knee OA, fulfilling clinical radiology criteria, were recruited across UK primary and secondary care.
What did we find?
Methotrexate added to usual care demonstrated significant reduction in knee OA pain at six months, and significant improvements in pain, stiffness and function. Despite a moderate standard effect size, the analgesic effect was of borderline clinical meaningfulness.
Outputs
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Publications
Kingsbury SR, Tharmanathan P, Arden NK, et al. Pain reduction with oral methotrexate in knee osteoarthritis, a pragmatic phase iii trial of treatment effectiveness (PROMOTE): study protocol for a randomized controlled trial. Trials. 2015 Mar 4;16:77. https://doi.org/10.1186/s13063-015-0602-8 PMID: 25872649
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Presentations
Kingsbury SR, Tharmanathan P, Keding A, et al. Significant pain reduction with oral methotrexate in knee osteoarthritis; results from the promote randomised controlled phase iii trial of treatment effectiveness. 2019 Osteoarthritis Research Society International (OARSI) World Congress in Toronto, Canada. Abstract. Volume 27, Supp 1, S84-S85, https://www.oarsijournal.com/issue/S1063-4584(19)X0004-7
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Team
Department of Health Sciences, University of York, York
- Sarah R Kingsbury
- Philip G Conaghan
- Andrew J Grainger
Division of Rheumatic and Musculoskeletal Disease and National Institute of Health Research (NIHR) Leeds Musculoskeletal Biomedical Research Unit, University of Leeds, Leeds
- Nigel K Arden
NIHR Musculoskeletal Biomedical Research Unit, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Nuffield Orthopaedic Centre, University of Oxford, Oxford
- Michael Batley
Department of Rheumatology, Maidstone and Tunbridge Wells NHS Trust, Pembury, Tunbridge Wells, Kent
- Fraser Birrell
Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle, UK
- Michael Doherty
Academic Rheumatology, University of Nottingham, Nottingham
- Chris J Edwards
Department of Rheumatology and NIHR Wellcome Trust Clinical Research Facility, University Hospital Southampton NHS Foundation Trust, Southampton
- Toby Garrood
Guy’s and St Thomas’ Hospitals Foundation NHS Trust, London,
- Michael Green
York Hospitals NHS Foundation Trust, Wigginton Road, York,
- Rod Hughes
Rheumatology Department, St Peters Hospital, Guildford Road, Chertsey, Surrey,
- Robert Moots
Institute of Integrative Biology, University of Liverpool and Institute of Ageing and Chronic Disease, University Hospital Aintree, Liverpool
- Terence W O’Neill
Arthritis Research UK Epidemiology Unit, University of Manchester, Manchester
- Edward Roddy
Research Institute for Primary Care and Health Sciences, Keele University, Keele
- David L Scott
Department of Rheumatology, King’s College London School of Medicine, King’s College London and Department of Rheumatology, King’s College Hospital, London
- Fiona E Watt
Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, and Imperial College London, London
Funding
The research was funded by an Arthritis Research UK Clinical Studies Grant (reference number: 20186). The project was started in October 2012 and completed in September 2016.
Study Registration
ISRCTN77854383 (registered: 25 October 2013).
