A Study of Tocilizumab (RoActemra/Actemra) in Monotherapy or in Combination With Methotrexate or Other Non-Biologic DMARDs in Participants With Active Rheumatoid Arthritis and an Inadequate Response to Current Non-Biologic DMARD Therapy or the First Anti-TNF Biologic Agent
Condition: Rheumatoid Arthritis
MeSH terms: Arthritis; Arthritis, Rheumatoid
Intervention: Tocilizumab; DMARDs; Oral Corticosteroids; Methotrexate
Intervention description: Tocilizumab 162 mg will be administered once a week by SC injection and as a single fixed dose, irrespective of body weight, for the treatment duration of 52 weeks.; Treatment with non-biologic DMARDs, at a stable dose that was initiated at least 4 weeks prior to baseline, is permitted during the study. The study protocol does not specify any particular therapy.; Stable oral corticosteroids doses (≤10 mg/day prednisone or equivalent) are allowed. The study protocol does not specify any additional detail on types of oral corticosteroids.; Methotrexate per investigator's discretion.
Intervention MeSH terms: Methotrexate
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 162.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This open-label study will evaluate the efficacy and safety of tocilizumab as monotherapy or
      in combination with methotrexate or other non-biologic disease modifying anti-rheumatic drugs
      (DMARDs) in participants with active rheumatoid arthritis (RA) and an inadequate response to
      current non-biologic DMARD therapy or the first anti-tumour necrosis factor (anti-TNF) agent.
      Participants will receive tocilizumab 162 milligrams (mg) subcutaneously once a week for 52
      weeks.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Active RA according to the revised (1987) ACR criteria or EULAR/ACR (2010) criteria

          -  Participants who have an inadequate response to current non-biologic DMARD therapy or
             the first anti-TNF agent (in monotherapy or in combination with MTX or other
             non-biologic DMARDs). Inadequate response to anti-TNF treatment is defined as DAS28
             score improvement of less than 1.2 or participants achieving a DAS28 score improvement
             of 1.2 but not achieving low disease activity (current DAS28-ESR above 3.2) according
             to a treat-to-target strategy and have not been previously exposed to treatment with
             tocilizumab. Inadequate response to non-biologic DMARD therapy will be assessed
             according to local guidelines and the participants will need to be eligible for
             biologic therapy according to local guidelines

          -  Oral corticosteroids (≤10 mg/day prednisone or equivalent) and non-steroidal
             anti-inflammatory drugs (NSAIDs; up to recommended dose) are permitted if on stable
             dose regimen for greater than or equal to [≥] 4 weeks prior to baseline

          -  Permitted non-biologic DMARDs are allowed if on stable dose for at least 4 weeks prior
             to baseline

          -  Receiving treatment on an outpatient basis, not including tocilizumab

          -  Females of childbearing potential and males with female partners of childbearing
             potential must agree to use reliable means of contraception as defined by protocol
             during the study and for at least 3 months following the last dose of tocilizumab

        Exclusion Criteria:

          -  Major surgery (including joint surgery) within 8 weeks prior to screening or planned
             major surgery within 6 months following baseline

          -  Rheumatic autoimmune disease other than RA

          -  Functional Class IV as defined by the ACR Classification of Functional Status in
             Rheumatoid Arthritis

          -  Diagnosis of juvenile idiopathic arthritis or juvenile RA and/or RA before the age of
             16

          -  Prior history of or current inflammatory joint disease other than RA

          -  Exposure to tocilizumab either intravenous or SC at any time prior to baseline

          -  Treatment with any investigational agent within 4 weeks (or 5 half-lives of the
             investigational drug, whichever is longer) of screening

          -  Intra-articular or parenteral corticosteroids within 4 weeks prior to baseline

          -  History of severe allergic or anaphylactic reactions to human, humanized or murine
             monoclonal antibodies

          -  Known active current or history of recurrent infections

          -  Major episode of infection requiring hospitalization or treatment with IV antibiotics
             within 4 weeks of screening or oral antibiotics within 2 weeks of screening

          -  Active tuberculosis (TB) requiring treatment within the previous 3 years

          -  Positive for hepatitis B or hepatitis C virus infection

          -  Primary or secondary immunodeficiency (history of or currently active)

          -  Pregnant or lactating women

          -  Inadequate hematologic, renal or liver function