MethMax trial

Prior treatment

• 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)
• Women of childbearing potential without 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 willingness to continue this precaution for the duration of the study until 6 months after receiving the last medication
• Presence of a transplanted solid organ (with the exception of a corneal transplant > 3 months prior to screening)
• 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.
• Immunization 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
• 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
• Patients with significant and clinically relevant MTX-drug toxicity as judged by the investigator

Other illness

• Inflammatory rheumatic diseases other than RA
• 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 other than TB) as judged by the investigator
• Current signs or symptoms of severe, progressive or uncontrolled renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, or cerebral disease, as judged by the investigator
• 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

Lab values

• 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)<60mL/min/1.73m2)

Other

• 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
• Women who are pregnant, nursing; or planning pregnancy during the study and 6 months after the individual study completion
• Active participation in any other interventional study
• Intraarticular GC treatment in the last 8 weeks
• Hematologic abnormalities (Grade 2 or 3: Anaemia, Leukopenia, Thrombocytopenia)

• 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 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