A Study of RoActemra/Actemra (Tocilizumab) in Combination With Methotrexate in Patients With Severe Active Rheumatoid Arthritis, Comparing Tapering Versus Maintaining the Methotrexate Dosage
Condition: Rheumatoid Arthritis
MeSH terms: Arthritis; Arthritis, Rheumatoid
Intervention: Methotrexate (stable dose); Tocilizumab; Methotrexate (tapering dose)
Intervention description: Methotrexate (MTX) was administered weekly according to the subject's pre-study MTX dose; 8 mg/kg intravenously every 4 weeks for 72 weeks; Tapering doses of methotrexate (MTX) were administered weekly from Week 24 to Week 56. Tapering doses depended on dose administered to the subject during the open label period. First tapering occurred at randomization (Week 24), second tapering at Week 32, third tapering at Week 40 and final tapering at Week 48.
Intervention MeSH terms: Methotrexate
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 427.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized, placebo-controlled, double-blind study will compare the safety and efficacy
      of tapering methotrexate (MTX) versus maintaining MTX dosage in patients with severe active
      rheumatoid arthritis and an inadequate response to disease-modifying antirheumatic drugs
      (DMARDs) initiated on treatment with tocilizumab. Participants will receive tocilizumab 8
      mg/kg intravenously every 4 weeks and MTX orally weekly throughout the study. At Week 24,
      participants achieving a good/moderate EULAR response will be randomized receiving the MTX
      Tapering arm or MTX Maintenance arm. Up to Week 56 participants will receive either tapering
      or stable dose MTX in combination with tocilizumab. From Week 56 to Week 72 participants will
      receive tocilizumab monotherapy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Adult patients, >/= 18 years of age

          -  Active severe rheumatoid arthritis (DAS28 > 5.1) according to European League of
             Rheumatism (EULAR)/American College of Rheumatology (ACR) criteria

          -  Inadequate response to a trial of 2 DMARDs, including methotrexate, a trial being
             defined as 6 months with 2 months at standard dose; no previous treatment with a
             biologic agent such as a tumor necrosis factor (TNF) inhibitor

          -  Oral corticosteroids must have been at a stable dose of </= 10 mg/day prednisolone or
             equivalent for at least 25 out of 28 days prior to start of treatment (Day 1)

        Exclusion Criteria:

          -  Major surgery (including joint surgery) within 8 weeks prior to screening or planned
             major surgery within 6 months following randomization

          -  Rheumatic autoimmune disease other than rheumatoid arthritis

          -  Functional class IV as defined by the ACR Classification of Functional Status in RA

          -  Prior history of or current inflammatory joint disease other than RA

          -  Previous treatment with tocilizumab

          -  Previous treatment with any biologic drug (e.g. TNF inhibitor) that is used in the
             treatment of RA

          -  Intraarticular or parenteral corticosteroids within 6 weeks prior to enrollment

          -  Inadequate liver, bone marrow or hepatic function

          -  Positive for hepatitis B, hepatitis C or HIV infection

          -  Pregnant or breastfeeding women

          -  Females of child-bearing potential who are not using reliable means of contraception

          -  History of severe allergic or anaphylactic reactions to human, humanized or murine
             monoclonal antibodies

          -  Active current or history of recurrent bacterial, viral, fungal, mycobacterial or
             other infections

          -  History of, or currently active, primary or secondary immunodeficiency