METHODS - A randomised controlled trial of METhotrexate to treat Hand Osteoarthritis with Synovitis: study protocol for a randomised controlled trial

Yuanyuan Wang,Andrew J Teichtahl,Jessica Kasza,Anita E Wluka,Flavia M Cicuttini,Catherine L Hill,Helen I Keen,Graeme Jones

doi:10.1186/s12891-021-04842-0

Abstract

BackgroundHand osteoarthritis is a common and disabling problem without effective therapies. Accumulating evidence suggests the role of local inflammation in causing pain and structural progression in hand osteoarthritis, and hand osteoarthritis with synovitis is a commonly encountered clinical phenotype. Methotrexate is a well-established, low-cost, and effective treatment for inflammatory arthritis with a well-described safety profile. The aim of this multicentre, randomised, double-blind, placebo-controlled trial is to determine whether methotrexate reduces pain over 6 months in patients with hand osteoarthritis and synovitis.MethodsNinety-six participants with hand osteoarthritis and synovitis will be recruited through the Osteoarthritis Clinical Trial Network (Melbourne, Hobart, Adelaide, and Perth), and randomly allocated in a 1:1 ratio to receive either methotrexate 20 mg or identical placebo once weekly for 6 months. The primary outcome is pain reduction (assessed by 100 mm visual analogue scale) at 6 months. The secondary outcomes include changes in physical function and quality of life assessed using Functional Index for Hand Osteoarthritis, Australian Canadian Osteoarthritis Hand Index, Health Assessment Questionnaire, Michigan Hand Outcomes Questionnaire, Short-Form-36, tender and swollen joint count, and grip strength, and structural progression assessed using progression of synovitis and bone marrow lesions from magnetic resonance imaging and radiographic progression at 6 months. Adverse events will be recorded. The primary analysis will be by intention to treat, including all participants in their randomised groups.DiscussionThis study will provide high-quality evidence to address whether methotrexate has an effect on reducing pain over 6 months in patients with hand osteoarthritis and synovitis, with major clinical and public health importance. While a positive trial will inform international clinical practice guidelines for the management of hand osteoarthritis, a negative trial would be highly topical and change current trends in clinical practice.Trial registrationAustralian New Zealand Clinical Trials Registry (ANZCTR), ACTRN12617000877381. Registered 15 June 2017, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=373124

Highlights

MethodsNinety-six participants with hand osteoarthritis and synovitis will be recruited through the Osteoarthritis Clinical Trial Network (Melbourne, Hobart, Adelaide, and Perth), and randomly allocated in a 1:1 ratio to receive either methotrexate 20 mg or identical placebo once weekly for 6 months
Hand osteoarthritis is a common and disabling problem without effective therapies
Hypothesis and objectives We propose a randomised, double-blind, placebo-controlled trial to determine the effect of 20 mg methotrexate weekly, compared to placebo, on reducing clinical symptoms and structural progression in people with hand OA and synovitis over 6 months

Summary

Methods

Study setting and participants Eligible participants with hand OA and synovitis will be recruited through the Osteoarthritis Clinical Trial Network (Melbourne, Hobart, Adelaide, and Perth, Australia), from the community via advertisements and from medical practitioners. MRI magnetic resonance imaging, VAS Visual Analogue Scale, AUSCAN Australian Canadian Osteoarthritis Hand Index, FIHOA Functional Index for Hand Osteoarthritis, HAQ Health Assessment Questionnaire, MHQ Michigan Hand Outcomes Questionnaire, WOMAC Western Ontario and McMaster Universities Osteoarthritis Index, AE adverse event a Baseline and follow-up x-ray performed at the same centre using a standardized protocol 1 To be performed/reviewed by study doctor 2 Full blood count, kidney function test, liver function test, C-reactive protein, erythrocyte sedimentation rate, rheumatoid factor, anti-cyclic citrullinated peptide antibodies, human immunodeficiency virus, Hepatitis B (sAb, sAg and cAb), Hepatitis C, and Quantiferon Gold 3 Full blood count, kidney function test, and liver function test 4 Not required if chest x-ray in last 12 months is available. Upon publication of the primary manuscript, participants will be informed of their group allocation and provided with the results

Discussion

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Findings