Methotrexate Alone Versus Combination of Methotrexate and Subcutaneous Fludarabine for Severe Rheumatoid Arthritis: Safety, Tolerance and Efficacy

Inclusion Criteria

• •Ability to provide informed consent to all aspects of the study after full information is provided.
• •Age equal to or older than 18.
• •A diagnosis of Rheumatoid Arthritis (RA) of more than 6 months as defined by the revised American College of Rheumatology criteria.
• •Active RA defined as: 6 or more swollen joints;
• •6 or more tender joints;
• •ESR greater than 28 mm/hr (or CRP greater than 0.8) or morning stiffness greater than 45 minutes.
• •Incomplete response (defined as persistently active disease as described above) to treatment with at least one of the following regimens for over 3 months:
• •MTX alone (greater than or equal to 17.5 mg/week);
• •MTX (greater than or equal to 17.5 mg/week) plus HCQ (greater than or equal to 200 mg/day);
• •MTX (greater than or equal to 17.5 mg/week) plus SSZ (greater than or equal to 1 gm/d);
• •MTX (greater than or equal to 17.5 mg/week) plus CsA (1-3 mg/kg/day);
• •MTX (greater than or equal to 17.5 mg/week) plus SSZ (greater than 1 gm/day) plus HCQ (greater than or equal to 200 mg/day);
• •No requirement of corticosteroids in doses equivalent to over 10 mg/d prednisone nor other immunosuppressive agents required for the control of extraarticular manifestations at the time of study entry.
• •No active acute or chronic infections requiring antibiotic therapy, serious viral infections (such as hepatitis, herpes zoster, or HIV), or serious fungal infections. Patients with a positive PPD who have not received INH or other antituberculous therapy will be excluded.
• •No pregnant women, nursing mothers, or patients of childbearing age not practicing birth control.
• •No preexisting malignancy other than basal cell carcinoma.
• •No history of stroke, seizure disorder, or chronic neurologic disease.
• •No unstable coronary artery disease, cardiomyopathy, conduction heart block greater than first degree, or a dysrhythmia requiring therapy.
• •No confounding medical illness that in the judgment of the investigators would pose added risk for study participants (e.g., chronic hepatic, renal, or pulmonary disease or bone marrow hypoplasia).
• •No presence of seronegative spondyloarthropathy, systemic lupus erythematosus, systemic sclerosis, inflammatory myopathy, systemic vasculitis, psoriasis, or inflammatory bowel disease.
• •No serum creatinine greater than 2.0 mg/dL on at least 2 different occasions which is sustained for at least 1 month.
• •No hematocrit less than 28% (or hemoglobin less than 9.0 mg/dL), or platelet count less than 100,000, or white blood count less than 3,500/dL.
• •No patients with active lung disease, patients with a chronic and progressive lung disease, or patients with a chronic but stable lung disease with pulmonary function tests of less than 70% of predicted (DLCO less than 60%).
• •No patients with hypogammaglobulinemia (IgG count less than 300).
• •No patients treated with alkylating agents for over 1 year at any time or treated with a purine nucleoside analog at any time.