Optimizing methotrexate therapy for rheumatoid arthritis patients

An International, Multicentre, Interventional, Randomised, Assessor-blinded Trial to MAXimise the METHotrexate Therapy Potential in Patients with Active Rheumatoid Arthritis

This study is testing whether giving methotrexate as a pill or an injection helps people with active rheumatoid arthritis feel better and respond to treatment more effectively.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 182 (estimated)
• Ages: 18 Years to 99 Years
• Sex: All
• Sponsor: Medical University of Vienna (Academic / other)
• Drugs / interventions: methotrexate
• Locations: 1 site (Vienna, State of Vienna)
• Trial ID: NCT06649136 on ClinicalTrials.gov

What this trial studies

The MethMax trial is an international, multicentre, randomised trial aimed at enhancing the effectiveness of methotrexate therapy in patients with active rheumatoid arthritis. Participants will be randomly assigned to receive either oral or subcutaneous methotrexate for 24 weeks, while their clinical outcomes, therapy adherence, and biomarkers will be closely monitored. The study seeks to identify factors that influence treatment response and optimize dosing and administration routes before considering more advanced therapies. This trial includes 182 patients across seven European countries and involves regular assessments at multiple time points.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with active rheumatoid arthritis who have been on stable oral methotrexate therapy for at least three months.

Not a fit: Patients with inflammatory rheumatic diseases other than rheumatoid arthritis or those who have previously received biologic or targeted synthetic DMARDs may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could improve treatment outcomes for patients with rheumatoid arthritis who are not achieving remission with current methotrexate therapy.

How similar studies have performed: Other studies have explored methotrexate optimization, but this specific approach of comparing oral versus subcutaneous administration is novel.

Eligibility criteria

Inclusion Criteria:

1. 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
2. Patients with rheumatoid arthritis (RA) according to the 2010 American College of Rheumatology/European Alliance of Associations for Rheumatology (ACR/EULAR) classification criteria
3. 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
4. CDAI \> 2.8 + at least 1 clinically swollen joint (on 28-Joint count)
5. Willingness to increase methotrexate dosing and change the route of administration according to study procedures

Exclusion Criteria:

1. Inflammatory rheumatic diseases other than RA
2. Ongoing or previous therapy with any biological DiseaseModifying Anti-Rheumatic Drug (bDMARDs) or targeted synthetic DMARDs (tsDMARDs) or conventional synthetic DMARDs (csDMARDs) other than methotrexate and hydroxychloroquine
3. Use of GC unless on stable oral dose ≤10mg for at least 4 weeks prior to study inclusion
4. Patients using NSAIDs, unless taken at a stable dose for ≥2 weeks prior to study inclusion
5. Intraarticular GC treatment in the last 8 weeks
6. Patients with significant and clinically relevant MTX-drug toxicity as judged by the investigator
7. Elevated liver enzymes (aspartate transaminase (ASAT) and/or alanine transaminase (ALAT)), and/or alkaline phosphatase (AP), and/or gamma-glutamyl transferase (GGT) above 2x the upper limit normal (ULN)
8. Reduced kidney function (glomerular filtration rate (GFR)\<60)
9. Haematologic abnormalities (grade 2 or 3: anaemia, leukopenia, thrombocytopenia)
10. Stomatitis under the treatment with MTX
11. Known history of recurrent/serious infections in the previous two months (such as, but not limited to, hepatitis, pneumonia, or pyelonephritis)
12. A positive HBsAg and/or HCV test at screening visit
13. Ongoing or recurring opportunistic infections (e.g., herpes zoster, cytomegalovirus, pneumocystis, aspergillosis, histoplasmosis, or mycobacteria) as judged by the investigator
14. Women of childbearing potential without the use of adequate birth control measures (e.g., abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, implantable or injectable contraceptives or surgical sterilization) and willing to continue this precaution for the duration of the study until 6 months after receiving the last medication
15. Current signs or symptoms of severe, progressive or uncontrolled renal, hepatic, haematologic, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, or cerebral disease, as judged by the investigator
16. Being unable or unwilling to undergo multiple venepunctures because of poor tolerability or lack of sufficient venous access
17. Being unwilling or unable to perform s.c injections
18. Presence of a transplanted solid organ (with the exception of a corneal transplant \> 3 months prior to screening)
19. Women who are pregnant, nursing; or planning pregnancy during the study and 6 months after the individual study completion
20. History of alcohol or substance abuse within the preceding 6 months
21. Any medical or psychological condition that, judged by the investigator, would interfere with safe completion of the trial
22. Immunisation with a live/attenuated vaccine within 12 weeks prior to baseline or potential need to receive a live vaccine during the course of the study
23. Active participation in any other interventional study

Where this trial is running

Vienna, State of Vienna

• Medical University of Vienna — Vienna, State of Vienna, Austria (Recruiting)

Conditions Rheumatoid Arthritis; rheumatoid arthritis; methotrexate; therapy adherence; biomarker