The 3TR Molecular PAthobiology and PRecision Therapy iN EaRly Rheumatoid Arthritis Study (3TR-PARTNER-RA)
Rheumatoid arthritis
Intervention Arm (Abatacept and Methotrexate): Abatacept: 125 mg solution for injection, subcutaneous, weekly. Methotrexate: Dose according to local guidelines. Control Arm (Placebo and Methotrexate): Placebo: Matching placebo injection, subcutaneous, weekly. Methotrexate: Dose according to local guidelines.
1. Adults (female and male) aged 18 years or over. 2. Willing and capable of giving informed consent. 3. 2010 ACR / EULAR classification criteria for a diagnosis of Rheumatoid Arthritis. * 4. Symptom duration of <12 months 5. At least one swollen joint, which is amenable to synovial biopsy (minimum grade 2 synovial thickening, as assessed at the biopsy visit). 6. Moderate and severe Disease Activity (DAS28>3.2) 7. No prior DMARD therapies (conventional, targeted or biologic DMARDs) 8. Patient is judged by the supervising clinician to be a suitable candidate based upon medical history, physical examination, vital signs, and routine laboratory tests. 9. Willing and able to comply with scheduled visits, laboratory tests, and other study procedures. * The ACR/EULAR classification for a diagnosis of RA could have been at any time in the patient’s disease history; the score does not need to be 6 or more at screening.
1. 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. 2. Patients in whom there is no suitable joint for biopsy. 3. Hypersensitivity to the active substance or to any of the excipients of abatacept or methotrexate, or any other contraindications to the study medications, as per the current SmPC. 4. 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). 5. Prior exposure to any biologic/targeted DMARDs for RA 6. Treatment with any investigational agent ≤ 8 weeks prior to baseline or < 5 half-lives of the investigational drug (whichever is the longer) 7. Intra-articular or parenteral corticosteroids, or oral prednisolone more than 10mg/d or equivalent ≤ 4 weeks prior to screening visit. 8. Patients with a serious underlying medical disorder (e.g., end stage renal disease). 9. Active infection 10. Subject has a history or known presence of recurrent or chronic infection (eg, hepatitis B virus [HBV], hepatitis C virus [HCV], human immunodeficiency virus HIV]; recurrent urinary tract infections are allowed. 11. Subjects testing positive for acute or chronic hepatitis A, B, or C, unless they are indicative of prior hepatitis B vaccination or cured hepatitis A or B and accompanied by normal liver transaminase values. 12. Septic arthritis of a native joint within the last 12 months 13. Septic arthritis of a prosthetic joint within 12 months or indefinitely if the joint remains in situ 14. Latent TB infection unless they have completed adequate antibiotic prophylaxis 15. Re