An international, multicentre, interventional, randomised, assessor-blinded trial to MAXimise the METHotrexate therapy potential in patients with active rheumatoid arthritis (MethMax trial): study protocol for a randomised controlled trial
Trials, vol. 27
Abstract
BACKGROUND: Methotrexate (MTX) is recommended as first-line therapy in patients with rheumatoid arthritis (RA), proven to be effective, safe and inexpensive. However, a significant proportion of patients does not achieve disease remission with MTX monotherapy. Main reasons include insufficient dose up-titration to the maximal recommended oral dose or the delayed switch to a subcutaneous administration route. We hypothesise, that by dose and route optimisation, a higher proportion of patients can achieve remission. Further, exploratory biomarkers will give new insights on individual MTX metabolism and drug adherence. METHODS: The MethMax trial is a prospective, randomised, assessor-blinded, parallel-group, superiority, low-intervention trial, including 182 patients across 7 European countries. Patients with active RA, naïve to biologic (except tumour necrosis factor alpha inhibitors; TNFi) or targeted synthetic antirheumatic drugs, who have been on a stable oral MTX therapy for the past 3 months are randomised in a 1:1 ratio to 25 mg MTX weekly, either administered orally or subcutaneously. Additionally, both arms receive a short-term glucocorticoid regimen with a four-week tapering and withdrawal protocol. The primary endpoint is the difference in proportion of patients achieving remission defined as the Clinical Disease Activity Index (CDAI) ≤ 2.8 at week 24, comparing the dose/route optimisation and oral dose optimisation. The active study duration for each patient is 24 weeks. Study visits take place at baseline, weeks 4, 12, 16 and 24. Clinical efficacy and safety parameters are obtained at each visit. Patient-reported outcomes, exploratory biomarkers as well as medication adherence are assessed. Written consent is obtained for all participants. The study has received regulatory approval via the Clinical Trials Information System and Medicines and Healthcare products Regulatory Agency and has included the first patient in August 2024. DISCUSSION: The anticipated results will provide insights whether the subcutaneous administration of 25 mg MTX is advantageous in achieving CDAI remission when compared to the oral intake after 24 weeks and inform the community regarding the utility of established and newly developed biomarkers, as well as the potential impact of inadequate drug adherence. The MethMax study is aimed to optimise individual therapy in RA and provide more precise pharmacological MTX management recommendations.
Authors 19
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Affiliation as printed
Division of Rheumatology, Department of Internal Medicine III, Medical University of Vienna, Guertel 18-20, Vienna, A-1090, Austria
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Affiliation as printed
Division of Rheumatology, Department of Internal Medicine III, Medical University of Vienna, Guertel 18-20, Vienna, A-1090, Austria
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Affiliation as printed
Division of Rheumatology, Department of Internal Medicine III, Medical University of Vienna, Guertel 18-20, Vienna, A-1090, Austria
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Affiliation as printed
Division of Rheumatology, Department of Internal Medicine III, Medical University of Vienna, Guertel 18-20, Vienna, A-1090, Austria
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Affiliation as printed
Division of Rheumatology, Department of Internal Medicine III, Medical University of Vienna, Guertel 18-20, Vienna, A-1090, Austria
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Karolinska University Hospital · Karolinska Institutet
Affiliation as printed
Department of Medicine, Solna, Division of Rheumatology, Karolinska University Hospital at Karolinska Institutet, Stockholm, Sweden
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Leiden University Medical Center
Affiliation as printed
Department of Rheumatology, Leiden University Medical Center, Leiden, Netherlands
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Queen Mary University of London · Barts Health NHS Trust · William Harvey Research Institute
Affiliation as printed
Centre for Experimental Medicine and Rheumatology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London & NIHR BRC Barts Health NHS Trust, London, UK
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Affiliation as printed
Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway
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University of Oslo · Diakonhjemmet Hospital
Affiliation as printed
Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway
Faculty of Medicine, University of Oslo, Oslo, Norway
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Affiliation as printed
Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway
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Carol Davila University of Medicine and Pharmacy
Affiliation as printed
Center for Rheumatic Diseases, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
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Carol Davila University of Medicine and Pharmacy
Affiliation as printed
Center for Rheumatic Diseases, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
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Humanitas University · IRCCS Humanitas Research Hospital
Affiliation as printed
Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
Rheumatology and Clinical Immunology, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
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Affiliation as printed
Nursing Science, Department Public Health, Faculty of Medicine, University of Basel, Basel, BS, Switzerland
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Affiliation as printed
Nursing Science, Department Public Health, Faculty of Medicine, University of Basel, Basel, BS, Switzerland
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European League Against Rheumatism
Affiliation as printed
Patient Research Partner, EULAR, Nicosia, Cyprus
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Affiliation as printed
Division of Rheumatology, Department of Internal Medicine III, Medical University of Vienna, Guertel 18-20, Vienna, A-1090, Austria
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Helga Radner corresponding
Affiliation as printed
Division of Rheumatology, Department of Internal Medicine III, Medical University of Vienna, Guertel 18-20, Vienna, A-1090, Austria. helga.lechner-radner@meduniwien.ac.at
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