Mechanistic Studies of B- and T-Cell Function in RA Patients Treated With TNF Antagonists, Tocilizumab, or Abatacept (MAZERATI)

This is an interventional basic science trial for Rheumatoid Arthritis (RA) focused on measuring Rheumatoid arthritis, TNF inhibitors Read More

Inclusion Criteria:

• Diagnosis of RA by a physician as defined by the 1987 and/or 2010 ACR criteria.
• 18 years of age or less than or equal to 64 at the time of diagnosis of RA.
• RA Disease Activity CDAI > 10
• If using oral corticosteroids, must have been on stable dose (≤ 10 mg/day) for at least 2 weeks prior to study drug initiation.
• PPD negative or if PPD positive documentation of therapy with INH for at least 1 month prior to study initiation and negative chest x-ray.
• Must have been treated within the past year with either methotrexate (MTX), leflunomide (LEF), hydrochloroquine (HCQ) and/or sulfasalazine (SSZ) for ≥ 3 months.
• Prior or concurrent use of other oral DMARD therapy, including MTX, leflunomide, SSZ, and HCQ, is permitted. Patients taking oral DMARDs must be on stable doses of DMARDs for at least 4 weeks prior to study drug initiation. Subjects are not required to be taking an oral DMARD.

Exclusion Criteria:

• Use of cyclophosphamide, penicillamine, cyclosporine A, tacrolimus or gold therapy is not permitted in the 6 months prior to enrollment.
• Patients who are using or have used other biologic agents or tofacitinib concomitantly or prior to this study
• History of active and/or chronic infection such as hepatitis, pneumonia, pyelonephritis,herpetic infections or chronic skin infections and any active opportunistic infection, including but not limited to evidence of active cytomegalovirus, active Pneumocystis carinii, aspergillosis, histoplasmosis or atypical mycobacterium infection.
• Active TB or evidence of latent TB (positive PPD skin test or a history of old or latent TB on chest x-ray) without adequate therapy for TB.
• Pregnant or lactating women.
• Patients with current signs or symptoms of uncontrolled renal, gastrointestinal, endocrine, pulmonary, cardiac, neurologic or cerebral disease.
• Diagnosis of liver disease or elevated hepatic enzymes, as defined by ALT, AST or both >1.5 x the upper limit of normal (ULN) or total bilirubin > ULN.

• Any of the following hematologic abnormalities, confirmed by repeat tests:

  1. White blood count < 3,000/µL or > 14,000/µL
  2. Lymphocyte count <500/µL
  3. Platelet count < 100,000/µL
  4. Hemoglobin < 8.0 g/dL
  5. Neutrophil count < 2,000 cells/µL
• Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following randomization.
• Immunization with a live/attenuated vaccine within 2 months prior to baseline or 3 months of last study visit.
• History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies
• History of other malignancy within 5 years prior to screening, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or Stage I uterine cancer
• Patients with reproductive potential not willing to use an effective method of contraception
• History of alcohol, drug or chemical abuse with 1 year prior to screening