Rheumatoid ArthritisPhase 4MethMaxNCT06649136
MethMax Trial: MAXimising the METHotrexate Therapy Potential in Patients With Active Rheumatoid Arthritis
A Phase 4 study testing Methotrexate in people with Rheumatoid Arthritis, run by Medical University of Vienna at 1 site in Austria.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- Methotrexate
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 182 participants
- Where
- 1 siteAustria
- Study dates
- 12 Aug 2024to 7 Jun 2027
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
- Willingness to increase methotrexate dosing and change the route of administration according to study procedures
Who cannot join
- 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
- Intraarticular GC treatment in the last 8 weeks
- Patients with significant and clinically relevant MTX-drug toxicity as judged by the investigator
Show all 23Show fewer
- 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)
- Reduced kidney function (glomerular filtration rate (GFR)<60)
- Haematologic abnormalities (grade 2 or 3: anaemia, leukopenia, thrombocytopenia)
- Stomatitis under the treatment with MTX
- Known history of recurrent/serious infections in the previous two months (such as, but not limited to, hepatitis, pneumonia, or pyelonephritis)
- A positive HBsAg and/or HCV test at screening visit
- Ongoing or recurring opportunistic infections (e.g., herpes zoster, cytomegalovirus, pneumocystis, aspergillosis, histoplasmosis, or mycobacteria) as judged by the investigator
- 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
- 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
- Being unable or unwilling to undergo multiple venepunctures because of poor tolerability or lack of sufficient venous access
- Being unwilling or unable to perform s.c injections
- Presence of a transplanted solid organ (with the exception of a corneal transplant > 3 months prior to screening)
- Women who are pregnant, nursing; or planning pregnancy during the study and 6 months after the individual study completion
- History of alcohol or substance abuse within the preceding 6 months
- Any medical or psychological condition that, judged by the investigator, would interfere with safe completion of the trial
- 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
- Active participation in any other interventional study
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Helga Lechner-Radner, Assoc.- Prof., PD, MD contact
Karolina Anderle, MD contact
Austria1 site, 1 recruiting
- Recruiting
Medical University of Vienna
Vienna, State of Vienna, 1090
Helga Lechner-Radner, MD, +43 (0)1 40400-43071, helga.lechner-radner@meduniwien.ac.at
Karolina Anderle, MD, Assoc.-Prof., +43 (0)1 40400-43071, karolina.anderle@meduniwien.ac.at
About this study
Official title: An International, Multicentre, Interventional, Randomised, Assessor-blinded Trial to MAXimise the METHotrexate Therapy Potential in Patients With Active Rheumatoid Arthritis
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.
Read the detailed description
Methotrexate is recommended as the first-line therapy in patients with rheumatoid arthritis. However, a significant proportion of patients does not achieve disease remission with methotrexate monotherapy, which can be attributed to multiple reasons. We hypothesize, that the efficacy limitations of this well-known medication can be, to some extent, overcome by sufficient dose and route optimisation. Furthermore, individual factors effecting the treatment response are unknown. Thus, we aim to evaluate the "maximised methotrexate therapy" before switching to biologic or targeted synthetic drugs.
The MethMax trial is a prospective, randomised, assessor-blinded, parallel-group, low-intervention trial, including 182 patients across 7 European countries. Patients with active rheumatoid arthritis, naïve to biologic or targeted synthetic antirheumatic drugs, who have been on a stable oral methotrexate therapy for the past 3 months will be randomised in 1:1 ratio to either 25 mg oral or 25 mg subcutaneous methotrexate weekly. In both arms, a short glucocorticoid therapy will be prescribed at baseline visit. The active study duration for each patient is 24 weeks. After inclusion, study visits take place at baseline, weeks 4, 12, 16 and 24. The clinical efficacy and safety parameters will be obtained at each visit. At predefined timepoints, further patient reported outcomes, exploratory biomarkers like sweat and blood metabolites, as well as medication adherence will be assessed. Written consent will be obtained for all participants. The study has received regulatory approval via the Clinical Trials Information System and hasstarted recruitment in August 2024.
The anticipated results will suggest whether the subcutaneous administration of 25 mg methotrexate weekly is superior to oral methotrexate 25 mg and lower doses in each route respectively. The outcomes include clinical disease activity, methotrexate metabolism analyses and medication adherence. The gained knowledge could lead to individual therapy optimisation and new therapy recommendations.
- Conditions
- Rheumatoid Arthritis
- Being tested
- Methotrexate
- Keywords
- rheumatoid arthritis, methotrexate, therapy adherence, biomarker
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MethotrexateDrug
comparison between oral and subcutaneous methotrexate dosis of 25mg
| Study group | Role | What they receive |
|---|---|---|
| methotrexate 25mg s.c. | Active comparator | methotrexate 25mg s.c. weekly dose Receives: Drug: Methotrexate |
| methotrexate 25mg p.o. | Active comparator | methotrexate 25mg p.o. weekly dose Receives: Drug: Methotrexate |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 24 weeks
Secondary outcomes (15)
CDAI low disease activity (≤10) at week 24
To assess the proportion of patients in CDAI low disease activity (≤10) at week 24
Measured: 24 weeks
CDAI remission (≤2.8) at week 12
To assess the proportion of patients in CDAI remission (≤2.8) at week 12
Measured: 12 weeks
CDAI low disease activity (≤10) at week 12
To assess the proportion of patients in CDAI low disease activity (≤10) at week 12
Measured: 12 weeks
ACR20% response at week 24
To assess the proportion of patients achieving an ACR20% response at week 24
Measured: 24 weeks
ACR20% response at week 12
To assess the proportion of patients achieving an ACR20% response at week 12
Measured: 12 weeks
ACR50% response at week 24
To assess the proportion of patients achieving an ACR50% response at week 24
Measured: 24 weeks
ACR50% response at week 12
To assess the proportion of patients achieving an ACR50% response at week 12
Measured: 12 weeks
ACR70% response at week 24
To assess the proportion of patients achieving an ACR70% response at week 24
Measured: 24 weeks
ACR70% response at week 12
To assess the proportion of patients achieving an ACR70% response at week 12
Measured: 12 weeks
Patient reported outcomes on NRS
Difference in change (absolute and relative) of patient reported outcomes on numeric response scale (NRS), including pain, patient global assessment, and joint stiffness between the treatment groups between baseline and week 24
Measured: 24 weeks
Patient reported outcomes on NRS
Difference in change (absolute and relative) of patient reported outcomes on numeric response scale (NRS), including pain, patient global assessment, and joint stiffness between the treatment groups between baseline and week 24
Measured: 12 weeks
Quality of Life questionnaires
Difference in change (absolute and relative) of patient reported outcomes measured by questionnaires:
- Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F)
- the 36-Item Short Form Survey version 1 (SF36v1)
- The Health Assessment Questionnaire Disability Index (HAQ-DI) between the treatment groups between baseline and week 12
Measured: 24 weeks
Quality of Life questionnaires
Difference in change (absolute and relative) of patient reported outcomes measured by questionnaires:
- Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F)
- the 36-Item Short Form Survey version 1 (SF36v1)
- The Health Assessment Questionnaire Disability Index (HAQ-DI) between the treatment groups between baseline and week 12
Measured: 12 weeks
Joint count and inflammatory markers
Difference in change (absolute and relative) of swollen joint count, tender joint count and CRP/ESR between baseline and week 24
Measured: 24 weeks
Joint count and inflammatory markers
Difference in change (absolute and relative) of swollen joint count, tender joint count and CRP/ESR between baseline and week 12
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2024
- Study start12 Aug 2024
- Primary completion7 Jun 2027 (estimated)
- Study completion7 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- More trials run by Medical University of ViennaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 182 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Medical University of Vienna
- Sponsor type
- University, hospital or other
- Collaborators
- Leiden University Medical Center, Queen Mary University of London, Carol Davila University of Medicine and Pharmacy, Clinical Centre for Rheumatic Diseases, Bucharest, Humanitas Mirasole S.p.A. - Instituto Clinico Humanitas (ICH), Rozzano (Milan), Region Stockholm, Solna, Diakonhjemmet Hospital AS (DH), Oslo
- Responsible party
- Principal investigator, Helga Lechner-Radner, Medical University of Vienna
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06649136
- Sponsor's protocol ID
- MethMax Trial
- Acronym
- MethMax
- Status last verified
- Oct 2026
- First submitted
- 15 Oct 2024
- Last updated
- 6 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: upon reasonable request
Study at a glance
From the registry record, last updated by the sponsor on 6 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An International, Multicentre, Interventional, Randomised, Assessor-blinded Trial to MAXimise the METHotrexate Therapy Potential in Patients With Active Rheumatoid Arthritis
- ClinicalTrials.gov ID
- NCT06649136
- Acronym / sponsor ID
- MethMax / MethMax Trial
- Conditions
- Rheumatoid Arthritis
- Keywords
- rheumatoid arthritis, methotrexate, therapy adherence, biomarker
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 182 participants (estimated)
- Lead sponsor
- Medical University of ViennaUniversity, hospital or other
- Collaborators
- Leiden University Medical Center, Queen Mary University of London, Carol Davila University of Medicine and Pharmacy, Clinical Centre for Rheumatic Diseases, Bucharest, Humanitas Mirasole S.p.A. - Instituto Clinico Humanitas (ICH), Rozzano (Milan), Region Stockholm, Solna, Diakonhjemmet Hospital AS (DH), Oslo
- Study start
- 12 Aug 2024 (actual)
- Primary completion
- 7 Jun 2027 (estimated)
- Study completion
- 7 Jun 2027 (estimated)
- First posted
- 18 Oct 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Methotrexate is recommended as the first-line therapy in patients with rheumatoid arthritis. However, a significant proportion of patients does not achieve disease remission with methotrexate monotherapy, which can be attributed to multiple reasons. We hypothesize, that the efficacy limitations of this well-known medication can be, to some extent, overcome by sufficient dose and route optimisation. Furthermore, individual factors effecting the treatment response are unknown. Thus, we aim to evaluate the "maximised methotrexate therapy" before switching to biologic or targeted synthetic drugs.
The MethMax trial is a prospective, randomised, assessor-blinded, parallel-group, low-intervention trial, including 182 patients across 7 European countries. Patients with active rheumatoid arthritis, naïve to biologic or targeted synthetic antirheumatic drugs, who have been on a stable oral methotrexate therapy for the past 3 months will be randomised in 1:1 ratio to either 25 mg oral or 25 mg subcutaneous methotrexate weekly. In both arms, a short glucocorticoid therapy will be prescribed at baseline visit. The active study duration for each patient is 24 weeks. After inclusion, study visits take place at baseline, weeks 4, 12, 16 and 24. The clinical efficacy and safety parameters will be obtained at each visit. At predefined timepoints, further patient reported outcomes, exploratory biomarkers like sweat and blood metabolites, as well as medication adherence will be assessed. Written consent will be obtained for all participants. The study has received regulatory approval via the Clinical Trials Information System and hasstarted recruitment in August 2024.
The anticipated results will suggest whether the subcutaneous administration of 25 mg methotrexate weekly is superior to oral methotrexate 25 mg and lower doses in each route respectively. The outcomes include clinical disease activity, methotrexate metabolism analyses and medication adherence. The gained knowledge could lead to individual therapy optimisation and new therapy recommendations.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| methotrexate 25mg s.c. | Active comparator | Drug: Methotrexatemethotrexate 25mg s.c. weekly dose |
| methotrexate 25mg p.o. | Active comparator | Drug: Methotrexatemethotrexate 25mg p.o. weekly dose |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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)
- Willingness to increase methotrexate dosing and change the route of administration according to study procedures
Key exclusion criteria (23 listed)
- 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
- Intraarticular GC treatment in the last 8 weeks
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Methotrexatecomparison between oral and subcutaneous methotrexate dosis of 25mg | Drug | methotrexate 25mg p.o., methotrexate 25mg s.c. |
Primary outcome
CDAI remission (≤2.8) at week 24
Time frame: 24 weeks
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).
15 secondary outcomes
CDAI low disease activity (≤10) at week 24
Time frame: 24 weeks
CDAI remission (≤2.8) at week 12
Time frame: 12 weeks
CDAI low disease activity (≤10) at week 12
Time frame: 12 weeks
ACR20% response at week 24
Time frame: 24 weeks
ACR20% response at week 12
Time frame: 12 weeks
ACR50% response at week 24
Time frame: 24 weeks
ACR50% response at week 12
Time frame: 12 weeks
ACR70% response at week 24
Time frame: 24 weeks
ACR70% response at week 12
Time frame: 12 weeks
Patient reported outcomes on NRS
Time frame: 24 weeks
Patient reported outcomes on NRS
Time frame: 12 weeks
Quality of Life questionnaires
Time frame: 24 weeks
Quality of Life questionnaires
Time frame: 12 weeks
Joint count and inflammatory markers
Time frame: 24 weeks
Joint count and inflammatory markers
Time frame: 12 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Oct 2026.
- Individual participant dataSharing planned: No. upon reasonable request
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Helga Lechner-Radner, Assoc.- Prof., PD, MD contact
Karolina Anderle, MD contact
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Methotrexate in people with Rheumatoid Arthritis, run by Medical University of Vienna at 1 site in Austria.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 6 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Austria. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Helga Lechner-Radner, Assoc.- Prof., PD, MD (+43 1 40400 47313, helga.lechner-radner@meduniwien.ac.at), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
CDAI remission (≤2.8) at week 24 (time frame: 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Oct 2026.