TO ASSESS THE EFFICACY AND SAFETY OF PF-06650833, PF-06651600, AND TOFACITINIB ALONE AND IN COMBINATION IN PARTICIPANTS WITH ACTIVE RHEUMATOID ARTHRITIS WITH AN INADEQUATE RESPONSE TO METHOTREXATE

Inclusion Criteria

• Male or female participants between the ages of 18 and 70 years.
• Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
• Diagnosis of RA and meeting the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for RA with a Total Score ≥6/10.
• The participant has active disease at both Screening and Randomization, as defined by both: ≥6 joints tender or painful on motion, AND ≥6 joints swollen; and fulfills 1 of the following 2 criteria: High sensitivity C reactive protein (hsCRP) >7 mg/L at Screening (Visit 1) as performed by the central laboratory OR Erythrocyte sedimentation rate (ESR) (Westergren method) >28 mm h.

Exclusion Criteria

• Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or IP administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study.
• Participants with a known immunodeficiency disorder or a first degree relative with a hereditary immunodeficiency.
• Participants with any active or latent infections.
• Participants with positive hepatitis B surface antigen (HBsAg).
• Participants with positive HCV Ab tests will be reflex tested for HCV ribonucleic acid (HCV RNA).
• Any history of either untreated or inadequately treated latent or active tuberculosis (TB) infection, current treatment for active or latent TB infection or evidence of currently active TB,
• History of a major organ transplant (eg, heart, lung, kidney and liver) or hematopoietic stem cell/marrow transplant.
• History of severe allergic or anaphylactoid reaction to kinase inhibitors, or corticosteroid preparations.
• Known history of diverticulitis or symptomatic diverticulosis, perineal abscess or fistulae.
• Participants with malignancy or history of malignancy (including lymphoma, leukemia, or lymphoproliferative disease).
• Pre-existing chronic autoimmune disease (eg, inflammatory bowel disease, systemic lupus erythematosus, moderate-severe atopic dermatitis, dermatomyositis) other than RA. Secondary Sjogren's Syndrome (due to RA) may be included.
• Participants with fibromyalgia will be excluded.
• Previous treatment with total lymphoid irradiation.
• Participants with an oral, tympanic, or temporal temperature of 38°C (100.4°F) or higher at baseline.
• Participants may not receive any live/attenuated vaccine from 30 days prior to randomization during the course of the study, or for 30 days after the last dose of study medication. Participants who have current routine household contact with children who have received varicella or oral polio vaccine within 2 months of first study dose are also excluded.
• History of any lymphoproliferative disorder.
• Have hearing loss with progression over the previous 5 years, sudden hearing loss, or middle or inner ear disease.
• History of any prior deep vein thrombosis (DVT) or pulmonary embolism [PE].
• Recent (within 6 months of screening) myocardial infarction, coronary revascularization, or percutaneous angioplasty with or without placement of a coronary artery stent; acute coronary syndrome; chronic uncompensated heart failure or New York Heart Association Functional Class III or IV; left ventricular assist devices; implanted defibrillators.
• Current severe chronic renal insufficiency or renal failure as defined by persistent (on repeated measurements) eGFR <60 mL/min per 1.73 m2 based on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) calculation.
• Any known coagulopathy or hypercoagulant syndrome.
• Presence of any of the following laboratory abnormalities at screening or within the 3 months prior to