The MethMax trial is a prospective, international, multicentre, randomised, assessor-blinded, parallel-group, low intervention study. Patients with active rheumatoid arthritis treated with oral methotrexate up to 25 mg weekly will be randomised in 50:50 fashion to receive 25 mg oral vs subcutaneous methotrexate for the period of 24 weeks. In regular visits, patient reported outcomes, clinical disease activity, therapy adherence and diverse established and exploratory biomarkers will be assessed.
Men and women, ≥ 18 years of age, capable of understanding and signing an informed consent (including sufficient literacy and proficiency in the local language) and following the study procedures
Patients with rheumatoid arthritis (RA) according to the 2010 American College of Rheumatology/European Alliance of Associations for Rheumatology (ACR/EULAR) classification criteria
Ongoing conventional therapy with oral methotrexate (between ≥10mg and 25mg weekly) for ≥3 months with stable dosing, and clinical and laboratory tolerance of this treatment for at least 12 weeks
CDAI > 2.8 + at least 1 clinically swollen joint (on 28-Joint count)
Inflammatory rheumatic diseases other than RA
Ongoing or previous therapy with any targeted synthetic DMARDs (tsDMARD) or biological Disease-Modifying Anti-Rheumatic Drug (bDMARD) with the exception of any TNFα inhibitor in a stable dose and interval for at least 4 months; We allow ongoing or previous therapy with a conventional synthetic DMARD (csDMARD) with a stable dose in the past 4 months.
Use of GC unless on stable oral dose ≤10mg for at least 4 weeks prior to study inclusion
Patients using NSAIDs, unless taken at a stable dose for ≥2 weeks prior to study inclusion
Parallel
Methotrexate
Drugcomparison between oral and subcutaneous methotrexate dosis of 25mg
CDAI remission (≤2.8) at week 24
The primary endpoint is the achievement of remission defined as the CDAI ≤2.8 assessed 24 weeks after randomisation comparing patients with dose/route optimization (≥10mg MTX oral weekly switched to 25mg MTX subcutaneously weekly) and oral dose optimization (≥10mg MTX oral weekly switched to 25mg MTX oral weekly).
CDAI low disease activity (≤10) at week 24
To assess the proportion of patients in CDAI low disease activity (≤10) at week 24
CDAI remission (≤2.8) at week 12
To assess the proportion of patients in CDAI remission (≤2.8) at week 12
CDAI low disease activity (≤10) at week 12
To assess the proportion of patients in CDAI low disease activity (≤10) at week 12
ACR20% response at week 24
To assess the proportion of patients achieving an ACR20% response at week 24
MTX-PGs levels and CDAI response
Association of MTX-PGs levels and CDAI response at week 12 and week 24
Therapeutic drug monitoring (MTX metabolites, TTV)
Association of MTX dosage, MTX-PGs levels and torque teno virus titer as a potential marker to guide levels of immunosuppressive therapy at week 12 and week 24
Finger sweat analysis
Association of MTX-metabolites and inflammatory markers in finger sweat analysis and CDAI at week 12 and week 24
Cumulative glucocorticoid dose
Difference in cumulative glucocorticoid (GC) dose between treatment arms
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Medical University of Vienna
Lead sponsor
Leiden University Medical Center
Collaborator
Queen Mary University of London
Collaborator
Carol Davila University of Medicine and Pharmacy, Clinical Centre for Rheumatic Diseases, Bucharest
Collaborator
Humanitas Mirasole S.p.A. - Instituto Clinico Humanitas (ICH), Rozzano (Milan)
Collaborator
Region Stockholm, Solna
Collaborator
Diakonhjemmet Hospital AS (DH), Oslo
Collaborator
