Methotrexate treatment in hand osteoarthritis refractory to usual treatments: A randomised, double-blind, placebo-controlled trial

Ferrero, S; Wittoek, Ruth; Allado, Edem; Cruzel, Coralie; Fontas, Éric; Breuil, Véronique; Ziegler, L. Euller; Kremer, Joel M.; Lœuille, Damien; Roux, Christian

doi:10.1016/j.semarthrit.2021.04.016

Cited by 40 publications

(22 citation statements)

References 39 publications

(41 reference statements)

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“…In agreement with these clinical trials on biologics, a recent study on HOA patients showed poorly detectable IL-1β concentrations and minimal inflammasome activity in the peripheral blood mononuclear cells of both erosive and non-erosive HOA patients [55]. Furthermore, the results derived from trials assessing the efficacy of the classical DMARDs, as hydroxychloroquine, methotrexate and colchicine, were not more positive [14,16,19,20,56]. Conversely, intravenous and intra-muscular clodronate, a first-generation bisphosphonate, currently registered in Europe for the treatment of postmenopausal osteoporosis, was demonstrated as effective in reducing pain and disability in patients with EHOA [57,58].…”

Section: Discussionmentioning

confidence: 56%

“…It is still highly debated if EHOA represents an advanced stage of the classical HOA or rather a separate entity with inflammatory features [7,8]. EHOA poses a significant clinical challenge, considering the substantial disability and the negative impact on quality of life (QoL), the paucity of symptomatic effective treatments and the lack of disease modifying antirheumatic drugs (DMARDs) [9][10][11][12][13][14][15][16][17][18][19][20].…”

Section: Introductionmentioning

confidence: 99%

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Prescription-grade crystalline glucosamine sulfate as an add-on therapy to conventional treatments in erosive osteoarthritis of the hand: results from a 6-month observational retrospective study

et al. 2022

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Objective To evaluate the efficacy of prescription-grade Crystalline Glucosamine Sulfate (pCGS) as an add-on treatment to conventional therapy, compared to usual therapy alone, in patients with erosive osteoarthritis of the hand (EHOA). Methods This 6-month retrospective case–control study included patients with concomitant knee osteoarthritis and symptomatic EHOA. Participants were stratified into two groups based on whether or not pCGS (1500 mg/day) was added to the conventional therapy (education and training in ergonomic principles, exercise and use on-demand of symptomatic drugs) for hand osteoarthritis. Patients were evaluated at baseline, after 3 and 6 months. Primary outcomes were the change from baseline to month 6 in Visual Analogue Scale (VAS) hand pain and in Functional Index for Hand Osteoarthritis (FIHOA) score. A set of secondary parameters was also evaluated. Results 123 patients were included as follows: 67 treated with pCGS in addition to conventional therapy (pCGS Group) and 56 with conventional therapy alone (Control Group). After 6 months a significant difference in VAS and in FIHOA score (p < 0.01 and p < 0.001, respectively) was observed in favor of pCGS Group. Similar results were found for morning stiffness duration (p < 0.05), health assessment questionnaire (p < 0.01) and physical and mental component score of 36-item short form (p < 0.05 and p < 0.001, respectively). A significant reduction of symptomatic drug consumption at 3 and 6 months was reported in the pCGS Group (p < 0.001). No serious adverse event was recorded in both groups. Conclusions Despite all the limitations inherent to an observational study, our results suggest the potential effectiveness of pCGS, when used in combination with conventional therapy in EHOA. Further randomized placebo-controlled trials are needed to confirm these positive findings. Trial Registration ClinicalTrials.gov, http://www.clinicaltrials.gov, date of registration: February 2, 2022, NCT05237596. The present trial was retrospectively registered.

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Section: Discussionmentioning

confidence: 56%

Section: Introductionmentioning

confidence: 99%

Prescription-grade crystalline glucosamine sulfate as an add-on therapy to conventional treatments in erosive osteoarthritis of the hand: results from a 6-month observational retrospective study

et al. 2022

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“… 36 A recent study on 64 participants with symptomatic erosive hand OA revealed no significant difference over the pain VAS (Visual Analogue Scale) score and functional outcomes on Functional Index for Hand Osteoarthritis [FIHOA] score at both 3- and 12-month follow-ups. 37 There was also no significant difference in structural progression evaluated by plain radiographs and MRI BMLs, erosions and synovitis. Currently, a phase III knee study is active for symptomatic OA patients with effusion-synovitis grade of ⩾2 (NCT03815448).…”

Section: Repurposed Drugs Already In Phase II and Iii Trials Either A...mentioning

confidence: 80%

“…Despite the immense success of DMARDs in the remission of disease activity in inflammatory arthritides such as RA, 83 neither conventional (i.e. MTX, 37 HCQ 40 ) nor biological DMARDs (i.e. etanercept, 96 tocilizumab 42 ) in recent clinical trials have brought success in improving either symptomatic or structural benefits or both in the case of predominantly inflammatory OA endotypes.…”

Section: Perspectivesmentioning

confidence: 99%

Repurposed and investigational disease-modifying drugs in osteoarthritis (DMOADs)

2022

Therapeutic Advances in Musculoskeletal

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In spite of a major public health burden with increasing prevalence, current osteoarthritis (OA) management is largely palliative with an unmet need for effective treatment. Both industry and academic researchers have invested a vast amount of time and financial expense to discover the first diseasing-modifying osteoarthritis drugs (DMOADs), with no regulatory success so far. In this narrative review, we discuss repurposed drugs as well as investigational agents which have progressed into phase II and III clinical trials based on three principal endotypes: bone-driven, synovitis-driven and cartilage-driven. Then, we will briefly describe the recent failures and lessons learned, promising findings from predefined post hoc analyses and insights gained, novel methodologies to enhance future success and steps underway to overcome regulatory hurdles.

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“…Methotrexate reduced pain in a randomised controlled trial over 6 months and an open-label trial over 24 weeks of knee OA [ 24 , 25 ]. However, a recently published randomised controlled trial showed no superiority of 10 mg methotrexate weekly over placebo in pain relief at 3 or 12 months in patients with symptomatic erosive hand OA refractory to usual treatments [ 26 ]. This study may be limited by the very low dose of methotrexate (10 mg weekly) and not inflammatory phenotype of hand OA being examined.…”

Section: Introductionmentioning

confidence: 99%

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

Wang

Teichtahl

Jones

et al. 2021

BMC Musculoskelet Disord

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Background Hand 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. Methods Ninety-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. Discussion This 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 registration Australian New Zealand Clinical Trials Registry (ANZCTR), ACTRN12617000877381. Registered 15 June 2017, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=373124

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Methotrexate treatment in hand osteoarthritis refractory to usual treatments: A randomised, double-blind, placebo-controlled trial

Cited by 40 publications

References 39 publications

Prescription-grade crystalline glucosamine sulfate as an add-on therapy to conventional treatments in erosive osteoarthritis of the hand: results from a 6-month observational retrospective study

Prescription-grade crystalline glucosamine sulfate as an add-on therapy to conventional treatments in erosive osteoarthritis of the hand: results from a 6-month observational retrospective study

Repurposed and investigational disease-modifying drugs in osteoarthritis (DMOADs)

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

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