A Study of the Safety and Efficacy of Rituximab in Patients With Moderate to Severe Rheumatoid Arthritis Receiving Methotrexate
Condition: Rheumatoid Arthritis
MeSH terms: Arthritis; Arthritis, Rheumatoid
Intervention: folate; methotrexate; methylprednisolone; Placebo; Rituximab
Intervention description: Minimum of 1 mg/day oral (or folinic acid 5 mg/week); 15-25 mg/week oral or parenteral (10-14 mg/week if intolerant); 100 mg intravenous (IV) prior to each rituximab infusion (For Arm B, for the Months 6 and 18 cycles, IV saline was administered prior to each placebo infusion); To maintain the blind, patients in Arm B (Rituximab 1000 mg) received placebo infusions at Months 6 and 18.; 500 mg or 1000 mg IV*2.
Intervention MeSH terms: Methylprednisolone; Rituximab; Methotrexate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 42.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Rituxan; RA

Summary:

      This was a Phase II, randomized, double-blind, multicenter study designed to evaluate the
      safety and efficacy of rituximab, administered at two different regimens for 2 years, in
      patients with moderate to severe active rheumatoid arthritis (RA) receiving stable doses of
      methotrexate (MTX).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of RA for at least 6 months.

          -  Inadequate response to MTX

          -  Use of folate

          -  If female and of childbearing potential, have a negative serum pregnancy test within 8
             weeks prior to first rituximab infusion

        Exclusion Criteria:

          -  Diagnosis of juvenile idiopathic arthritis (also known as juvenile rheumatoid
             arthritis) and/or RA before age 16

          -  Any surgical procedure, including bone/joint surgery or planned surgery within 8 weeks
             prior to screening or within 16 weeks of Week 1 (Day 1) visit

          -  Inflammatory arthritis other than RA (e.g., inflammatory bowel disease, systemic lupus
             erythematosus (SLE), or psoriatic arthritis)

          -  Functional Class IV as defined by the American College of Rheumatology (ACR)
             classification of functional status in RA

          -  Use of disease-modifying anti-rheumatic drugs (DMARDs) other than MTX within 4 weeks
             prior to randomization (8 weeks prior for infliximab, adalimumab, or leflunomide)

          -  Treatment with any investigational agent within 4 weeks of screening or 5 half-lives
             of the investigational drug (whichever is longer)

          -  Previous treatment with Tysabri<TM> (natalizumab)

          -  Previous treatment with rituximab

          -  Previous treatment with any cell-depleting therapies, including investigational agents

          -  Treatment with IV &-globulin or Prosorba(R) Column within the previous 6 months

          -  Use of intra-articular or parenteral corticosteroids within 4 weeks prior to screening
             visit

          -  Receipt of a vaccine within 4 weeks prior to Day 1 infusion

          -  History of severe allergic or anaphylactic reactions to humanized or murine monoclonal
             antibodies

          -  Primary or secondary immunodeficiency (history of or active)

          -  Evidence of significant uncontrolled concomitant diseases such as cardiovascular
             disease, nervous system, renal, hepatic, endocrine, gastrointestinal, or pulmonary
             disease, including any pulmonary or other condition that would preclude subject
             participation over the ensuing 2 years

          -  Known active bacterial, viral, fungal, mycobacterial, or other infection (including
             tuberculosis or atypical mycobacterial disease, but excluding fungal infections of
             nail beds)

          -  History of recurrent significant infection or any significant episode of infection
             requiring hospitalization or treatment with IV antibiotics within 4 weeks of screening
             or oral antibiotics within 2 weeks prior to screening

          -  History of significant cytopenias or other bone marrow disorders

          -  History of cancer, including solid tumors and hematologic malignancies (except basal
             cell and squamous cell carcinoma of the skin that have been excised and cured)

          -  Pregnant or nursing (breast feeding) women

          -  Lack of peripheral venous access

          -  Chronic daily use of narcotic analgesics

          -  History of alcohol, drug, or chemical abuse within 6 months prior to screening