TY - JOUR
T1 - Methotrexate to treat hand osteoarthritis with synovitis (METHODS)
T2 - an Australian, multisite, parallel-group, double-blind, randomised, placebo-controlled trial
AU - Wang, Yuanyuan
AU - Jones, Graeme
AU - Keen, Helen I.
AU - Hill, Catherine L.
AU - Wluka, Anita E.
AU - Kasza, Jessica
AU - Teichtahl, Andrew J.
AU - Antony, Benny
AU - O'Sullivan, Richard
AU - Cicuttini, Flavia M.
N1 - Funding Information:
The study is funded by a project grant from the National Health and Medical Research Council of Australia (NHMRC; APP1127981). YW receives funding from the NHMRC Translating Research into Practice Fellowship (APP1168185). GJ receives funding from the NHMRC Practitioner Fellowship. AEW receives funding from the Royal Australian College of Physicians Fellows Career Development Fellowship. FMC receives funding from the NHMRC Investigator Grant (APP1194829). We thank the study participants who made this study possible. We also thank Molly Bond, Cameron Redpath, Sin-Ki Ng, Aruna Kartik, Ekjyot Kaur, Yuan Lim, Sharmayne Brady, Louisa Chou, Mabel Yan, Kathy Buttigieg, Carlee Ruediger, Kathryn Dyer, and Daniel Lightowler for their compensated role in the coordination and execution of the study.
Publisher Copyright:
© 2023 Elsevier Ltd
PY - 2023/11/11
Y1 - 2023/11/11
N2 - Background: Hand osteoarthritis is a disabling condition with few effective therapies. Hand osteoarthritis with synovitis is a common inflammatory phenotype associated with pain. We aimed to examine the efficacy and safety of methotrexate at 6 months in participants with hand osteoarthritis and synovitis. Methods: In this multisite, parallel-group, double-blind, randomised, placebo-controlled trial, participants (aged 40–75 years) with hand osteoarthritis (Kellgren and Lawrence grade ≥2 in at least one joint) and MRI-detected synovitis of grade 1 or more were recruited from the community in Melbourne, Hobart, Adelaide, and Perth, Australia. Participants were randomly assigned (1:1) using block randomisation, stratified by study site and self-reported sex, to receive methotrexate 20 mg or identical placebo orally once weekly for 6 months. The primary outcome was pain reduction (measured with a 100 mm visual analogue scale; VAS) in the study hand at 6 months assessed in the intention-to-treat population. Safety outcomes were assessed in all randomly assigned participants. This trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12617000877381). Findings: Between Nov 22, 2017, and Nov 8, 2021, of 202 participants who were assessed for eligibility, 97 (48%) were randomly assigned to receive methotrexate (n=50) or placebo (n=47). 68 (70%) of 97 participants were female and 29 (30%) were male. 42 (84%) of 50 participants in the methotrexate group and 40 (85%) of 47 in the placebo group provided primary outcome data. The mean change in VAS pain at 6 months was –15·2 mm (SD 24·0) in the methotrexate group and –7·7 mm (25·3) in the placebo group, with a mean between-group difference of –9·9 (95% CI –19·3 to –0·6; p=0·037) and an effect size (standardised mean difference) of 0·45 (0·03 to 0·87). Adverse events occurred in 31 (62%) of 50 participants in the methotrexate group and 28 (60%) of 47 participants in the placebo group. Interpretation: Treatment of hand osteoarthritis and synovitis with 20 mg methotrexate for 6 months had a moderate but potentially clinically meaningful effect on reducing pain, providing proof of concept that methotrexate might have a role in the management of hand osteoarthritis with an inflammatory phenotype. Funding: National Health and Medical Research Council of Australia.
AB - Background: Hand osteoarthritis is a disabling condition with few effective therapies. Hand osteoarthritis with synovitis is a common inflammatory phenotype associated with pain. We aimed to examine the efficacy and safety of methotrexate at 6 months in participants with hand osteoarthritis and synovitis. Methods: In this multisite, parallel-group, double-blind, randomised, placebo-controlled trial, participants (aged 40–75 years) with hand osteoarthritis (Kellgren and Lawrence grade ≥2 in at least one joint) and MRI-detected synovitis of grade 1 or more were recruited from the community in Melbourne, Hobart, Adelaide, and Perth, Australia. Participants were randomly assigned (1:1) using block randomisation, stratified by study site and self-reported sex, to receive methotrexate 20 mg or identical placebo orally once weekly for 6 months. The primary outcome was pain reduction (measured with a 100 mm visual analogue scale; VAS) in the study hand at 6 months assessed in the intention-to-treat population. Safety outcomes were assessed in all randomly assigned participants. This trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12617000877381). Findings: Between Nov 22, 2017, and Nov 8, 2021, of 202 participants who were assessed for eligibility, 97 (48%) were randomly assigned to receive methotrexate (n=50) or placebo (n=47). 68 (70%) of 97 participants were female and 29 (30%) were male. 42 (84%) of 50 participants in the methotrexate group and 40 (85%) of 47 in the placebo group provided primary outcome data. The mean change in VAS pain at 6 months was –15·2 mm (SD 24·0) in the methotrexate group and –7·7 mm (25·3) in the placebo group, with a mean between-group difference of –9·9 (95% CI –19·3 to –0·6; p=0·037) and an effect size (standardised mean difference) of 0·45 (0·03 to 0·87). Adverse events occurred in 31 (62%) of 50 participants in the methotrexate group and 28 (60%) of 47 participants in the placebo group. Interpretation: Treatment of hand osteoarthritis and synovitis with 20 mg methotrexate for 6 months had a moderate but potentially clinically meaningful effect on reducing pain, providing proof of concept that methotrexate might have a role in the management of hand osteoarthritis with an inflammatory phenotype. Funding: National Health and Medical Research Council of Australia.
UR - http://www.scopus.com/inward/record.url?scp=85175568027&partnerID=8YFLogxK
U2 - 10.1016/S0140-6736(23)01572-6
DO - 10.1016/S0140-6736(23)01572-6
M3 - Article
C2 - 37839420
AN - SCOPUS:85175568027
SN - 0140-6736
VL - 402
SP - 1764
EP - 1772
JO - The Lancet
JF - The Lancet
IS - 10414
ER -