A Study of Rituximab (MabThera®/Rituxan®) in Patients With Rheumatoid Arthritis and Inadequate Response to Methotrexate
Condition: Rheumatoid Arthritis
MeSH terms: Arthritis; Arthritis, Rheumatoid
Study type: Interventional
Phase: Phase 3

Summary: 
      This 3 arm study assessed the efficacy of rituximab (MabThera®/Rituxan®) in the prevention of
      progression of structural joint damage in participants with active rheumatoid arthritis who
      had an inadequate clinical response to methotrexate. Participants were randomized to receive
      rituximab 500 mg intravenously (iv), rituximab 1000 mg iv, or placebo iv on days 1 and 15
      every 24 weeks in the main study; all participants received concomitant methotrexate at a
      stable dose of 12.5-25 mg/week throughout the study. Further courses of rituximab were
      provided to eligible participants. Structural joint damage was assessed by magnetic resonance
      imaging (MRI) at baseline and at intervals during the study.
    

Detailed description: 
      There were 3 phases in the study: A 52 week long main study, a study extension phase, and a
      48 week long safety follow-up phase.

      The first course of treatment with placebo or rituximab was initiated on Day 1 of the 52 week
      long main study. A second course of treatment was initiated after Week 24, if the participant
      met eligibility criteria. After Week 52, eligible participants received further treatment
      courses at intervals ≥ 6 months in the study extension phase. No treatments were administered
      in the safety follow-up phase.

      Participants had to meet the following eligibility criteria to receive rituximab in the study
      extension phase.

        -  Minimum of 24 weeks had passed since the first infusion of the last course of study
           medication.

        -  C-reactive protein-based Disease Activity Score 28 (DAS28-CRP) ≥ 2.6.

        -  Absolute neutrophil count not below 1.5 x 103/μL.

        -  Patient had not developed contraindications for receiving rituximab, such as:

             1. Any new or uncontrolled concomitant disease such as, but not limited to,
                cardiovascular disease, nervous system, pulmonary, renal, hepatic, endocrine or
                gastrointestinal disorders.

             2. Primary or secondary immunodeficiency (history of, or currently active), including
                known history of HIV infection.

             3. Known active infection of any kind (excluding fungal infections of nail beds), or
                any major episode of infection requiring hospitalization, or treatment with iv
                anti-infectives within 4 weeks prior to infusion or completion of oral
                anti-infectives within 2 weeks prior to infusion.

        -  Patient was not pregnant or breast feeding.

        -  Patients who entered the study and were found to be hepatitis B surface antigen (HBsAg)
           negative, hepatitis B core antibody (HBcAb) positive, were to be negative for hepatitis
           B viral DNA (< 29 IU/mL) and were to have aspartate aminotransferase (AST)/alanine
           aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN) results within the last 12
           weeks.
    

Intervention name(s): Rituximab; Placebo; Methylprednisolone; Methotrexate; Folic acid or folate
Intervention type(s): Biological; Drug; Drug; Drug; Drug
Intervention description(s): Rituximab was supplied as a sterile liquid for iv administration.; Placebo was supplied as a sterile liquid in single-use vials for iv administration.
Other intervention name(s): MabThera®; Rituxan®
Intervention MeSH terms: Folic Acid; Methylprednisolone; Rituximab; Methotrexate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment