Rheumatoid Arthritis: Comparison of Active Therapies in Patients With Active Disease Despite Methotrexate Therapy (RACAT)

This is an interventional treatment trial for Rheumatoid Arthritis focused on measuring antineoplastic, antiparasitics, antirheumatics, chronic diseases, clinical trial, connective tissue, double-blind, drug treatment, gastric medications, joint, multi-site trial, musculoskeletal, randomized, rheumatoid arthritis Read More

Inclusion Criteria:

• All patients must fulfill ACR classification criteria for rheumatoid arthritis.
• All patients must have been 16 years of age or older at time of diagnosis of rheumatoid arthritis.
• All patients must be 18 years of age or older at the time of entry into the study.
• All patients will have been receiving oral or subcutaneous methotrexate 15 to 25 mg/week (unless intolerant and on a minimum 10 mg/week) at a constant dose for at least 4 weeks, and on any methotrexate for no less than 12 weeks.
• All patients will have active disease as defined by a DAS28 of greater than or equal to 4.4.
• If patients are receiving corticosteroids, they must have been on stable dose (less than or equal to 10 mg prednisone or equivalent) for at least two weeks prior to screening.
• If patients are using non-steroidal anti-inflammatory drugs (NSAIDs), they must be on stable doses for at least one week prior to screening.
• If patients have taken leflunomide, cyclosporine, gold, Anakinra, azathioprine, or penicillamine in combination with methotrexate, they must have stopped this therapy at least 8 weeks prior to randomization.

• Laboratory tests must meet the following criteria within 2 weeks of randomization:

  • Serum creatinine 1.8 mg/dL
  • Hemoglobin 9 g/dL
  • WBC 3000 mc/L
  • Neutrophils 1000 mc/L
  • Platelets 100,000 mc/L
  • Serum transaminase level (AST or ALT, whichever is followed at the site) not exceeding 1.2 times upper limit of normal.
  • Albumin no less than 1.0 g/dL (10 g/L) below lower limit of normal. Anything below lower limit of normal must have been stable (or improving) for no less than 90 days. Stable is defined as changes of no more than 0.2 g/dL (2 g/L).
• All patients must be capable of giving informed consent and able to adhere to study visit schedule.
• Subject or designee must have the ability to self-inject investigational product or have a caregiver who can inject subcutaneous injections

• Subjects must meet one of the following criteria with regard to tuberculosis. PPD must be within 180 days of randomization if the patient has no recent exposure/travel history, or within 90 days if the patient has a recent exposure/travel history.

  • Negative PPD; or
  • Positive PPD <5 mm, with a negative chest x-ray; or
  • Positive PPD >5mm, treated for at least 28 days with INH.
• Subjects with an Erythrocyte sedimentation rate (ESR) of less than or equal to 10 and a tender and swollen joint count of at least 10 and does not qualify for the study using the DAS28, will be allowed to use the DAS28-CRP rather than the traditional DAS28 to determine eligibility.

Exclusion Criteria:

• Previous intolerance to methotrexate (unless able to tolerate at least 10 mg/week)
• Sensitivity to study medications
• Previous treatment with methotrexate, sulfasalazine or hydroxychloroquine in combination with each other for longer than 4 weeks duration. No combination use is allowed within 4 weeks of screening.
• No bed or wheelchair-bound patients

• Previous treatment with a TNF- inhibitor (etanercept, infliximab or adalimumab) for more than 5 weeks of therapy. Previous treatment with TNF- inhibitor must have been stopped for reasons other than toxicity or efficacy. No TNF- inhibitor therapy is allowed within the following time frames:

  • Last dose of etanercept must have been at least 4 weeks before screening.
  • Last dose of adalimumab or infliximab must have been at least 8 weeks prior to screening.

Example of an eligible patient: A patient found he could not afford the co-pays for a TNF inhibitor after two doses and stopped taking the medication two months before being evaluated for this trial.

• Evidence of important acute or chronic infections (no IV antibiotics within 1 month, and no PO antibiotics within 2 weeks)
• Pregnant or nursing women
• Women of childbearing potential or their partners who are not practicing an acceptable form of birth control as defined by investigator
• Active substance abuse or psychiatric illness likely to interfere with protocol completion
• History of multiple sclerosis, transverse myelitis, or optic neuritis
• History of macular degeneration unless patient has letter from their ophthalmologist that will allow for participation in trial
• New York Heart Association Class III or IV congestive heart failure
• Active malignancy (other than in situ cervical cancer or non-melanoma skin cancer), or history of lymphoma
• History of HIV
• History of any opportunistic infection - to include but not limited to Pneumocystis carinii, aspergillosis, histoplasmosis, or atypical mycobacterium
• History of porphyria
• Diagnosis of SLE or seronegative spondyloarthropathy or any other form of concomitant arthritis (osteoarthritis is permitted)
• Diagnosis of psoriasis unless rheumatoid factor positive
• Any significant unstable medical condition considered a contraindication by investigator
• Any participation in another investigational drug study during the 90 days preceding randomization.
• Receipt of a live vaccine within 90 days of study entry.
• History of oral or IV cyclophosphamide use
• Life expectancy less than 2 years
• Receipt of steroid injection, intravenous, intramuscular, or intraarticular, within 30 days of randomization.