The 3TR Molecular Pathobiology-Driven Precision Therapy in RA (3TR Precis-The-RA) study

Prior treatment

• Any other contra-indication to the study medications as detailed in the applicable SmPC
• Receipt of live vaccine <4 weeks prior to first dose of study medication
• Major surgery in 3 months prior to first dose of study medication
• Presence of a transplanted organ (with the exception of a corneal transplant >3 months prior to screening)
• Known recent substance abuse (drug or alcohol)
• Prior exposure to any biologic/targeted DMARDs for RA
• Treatment with any investigational agent ≤ 4 weeks prior to baseline or < 5 half-lives of the investigational drug (whichever is the longer)
• Intra-articular or parenteral corticosteroids ≤ 4 weeks prior to screening visit
• Oral prednisolone more than 10mg/d or equivalent ≤ 4 weeks prior to baseline synovial biopsy

Other illness

• Latent TB infection unless they have completed adequate antibiotic prophylaxis
• Malignancy (other than basal cell carcinoma) within the last 10 years
• New York Heart Association (NYHA) grade III or IV congestive heart failure
• Demyelinating disease
• Known allergy to latex, or known hypersensitivity to the study medication active substance or to any of the excipients of the IMP
• Patients with severe hepatic impairment (Child Pugh C classification)
• History of or current primary inflammatory joint disease or primary rheumatological autoimmune disease other than RA (if secondary to RA, then the patient is still eligible)
• Active infection
• Known HIV, active Hepatitis B/C infection. Hepatitis B screening test must be performed at or in the preceding 3 months of screening visit or in line with clinical practice

Lab values

• Patients unable to tolerate synovial biopsy or in whom this is contraindicated including patients on anti-coagulants (e.g. warfarin). Patients on short-acting direct oral anticoagulant agents can be considered when anti-coagulant can be temporarily stopped, in line with local guidelines for procedures with a low risk of bleeding, taking into account the individual thromboembolic risk. Oral anti-platelet agents are permitted
• Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that would impart, in the judgment of the investigator, excess risk associated with study participation or study drug administration, or which, in the judgment of the investigator, would make the patient inappropriate for entry into this study. This should include assessment of risk factors for known clinically important risks associated with a study drug

Other

• Women who are pregnant or breast-feeding
• Septic arthritis of a native joint within the last 12 months
• Septic arthritis of a prosthetic joint within 12 months or indefinitely if the joint remains in situ
• Women of child-bearing potential or males whose partners are women of child-bearing potential, unwilling to use an effective method of contraception (recommend double contraception) throughout the trial and beyond the end of trial treatment for the duration as defined in the relevant SmPC
• Poor tolerability of venepuncture or lack of adequate venous access for required blood sampling during the study period
• Patients currently recruited to other clinical trials
• Patients that are immunocompromised

• 2010 ACR / EULAR classification criteria for a diagnosis of Rheumatoid Arthritis
• Patients with csDMARD failure and eligible for anti-TNF therapy according to EULAR recommendations: treatment for ≥3months with ≥ 1 csDMARDs
• Patients must have a DAS>5.1 and a minimum of 3 swollen joints – where the patient is undergoing a biopsy at visit 2, these should include the joint selected for biopsy and 2 other joints, as assessed at biopsy visit
• Selected joint for biopsy must be minimum grade 2 synovial thickening, as assessed at the biopsy visit
• 18 years of age or over
• Patients must be capable of giving informed consent and the consent must be obtained prior to any screening procedures
• Willingness and ability to comply with scheduled visits, treatment plans and laboratory tests and other study procedures