MethMax Trial: MAXimising the METHotrexate Therapy Potential in Patients with Active Rheumatoid Arthritis

Exclusion Criteria23

• Inflammatory rheumatic diseases other than RA
• 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
• 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
• 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