Study to Compare the Efficacy of Tocilizumab With or Without Glucocorticoid Discontinuation in Rheumatoid Arthritis Participants
Condition: Rheumatoid Arthritis
MeSH terms: Arthritis; Arthritis, Rheumatoid
Intervention: Placebo matched to prednisone; Prednisone; Tocilizumab
Intervention description: Participants will receive placebo matched to prednisone orally for 24 weeks.; Participants will receive prednisone either at a constant dose of 5 mg/day, or 5 mg/day with 1 mg decrements every 4 weeks orally for 24 weeks.; Participants will receive tocilizumab at a dose of 162 mg once a week subcutaneously for 24 weeks.
Intervention MeSH terms: Prednisone
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 314.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This Phase IIIb/IV, two-arm, randomized, double-blind, placebo-controlled, parallel-group,
      international, multicenter trial compares the change in disease activity (as assessed by
      Disease Activity Score in 28 joints [DAS28] erythrocyte sedimentation rate [ESR]) from
      randomization to Week 24 post-randomization, in participants with stable low disease activity
      [LDA] (DAS28 ESR score less than or equal to [<=] 3.2) who receive tocilizumab, and have been
      randomized to either continue or taper prednisone in a double-blinded fashion.
    

Eligibility criteria:

        Inclusion Criteria:

        Tocilizumab-experienced participants:

          -  Comply with the requirements of the study protocol (including treatment on an
             outpatient basis)

          -  Rheumatoid arthritis (RA) of greater than or equal to (>=) 6 months duration diagnosed
             according to the revised 1987 American College of Rheumatology (ACR) criteria or 2010
             ACR / European League Against Rheumatism (EULAR) criteria

          -  Have received tocilizumab either subcutaneous (162 milligram [mg] once in a week) or
             intravenously (8 milligram per kilogram [mg/kg] once every 4 weeks) for the treatment
             of RA for at least 24 weeks prior to randomization

          -  Have received 5 - 15 milligrams per day [mg/day] of glucocorticoids (prednisone or
             equivalent) for the treatment of RA for at least 20 weeks prior to screening

          -  Currently receiving 5 mg/day of prednisone

          -  Have attained and maintained LDA (DAS28 ESR score <=3.2) or remission (DAS28 ESR score
             less than [<] 2.6) for at least 4 weeks prior to randomization

        Tocilizumab-naïve participants:

          -  Comply with the requirements of the study protocol (including treatment on an
             outpatient basis)

          -  RA of >=6 months duration diagnosed according to the revised 1987 ACR criteria or 2010
             ACR / EULAR criteria

          -  Have active RA (defined as DAS28 ESR score greater than [>] 3.2)

          -  Are considered by the investigator as inadequate responders to conventional synthetic
             disease-modifying anti-rheumatic drugs (csDMARDs) or biologic disease-modifying
             anti-rheumatic drugs (bDMARDs)

          -  Are receiving 5 - 15 mg/day prednisone (or equivalent) for the treatment of RA

        Exclusion Criteria:

        General

          -  Major surgery (including joint surgery) within 8 weeks prior to screening, or planned
             major surgery during the study and up to 6 months after randomization

          -  Pregnant women or nursing (breastfeeding) mothers

          -  In females of childbearing potential, a positive serum pregnancy test at screening

          -  Females of childbearing potential unwilling or unable to use a reliable means of
             contraception (for example, physical barrier [participant or partner], contraceptive
             pill or patch, spermicide and barrier, or intrauterine device) during study treatment
             and for a minimum of 3 months after the last dose of tocilizumab

          -  Body weight of >=150 kilogram (kg)

          -  Lack of peripheral venous access

        Disease-related

          -  RA of functional Class 4, as defined by the ACR Classification of Functional Status in
             Rheumatoid Arthritis

          -  Rheumatic autoimmune disease other than RA, including systemic lupus erythematosus,
             mixed connective tissue disease, scleroderma, polymyositis, or significant systemic
             involvement secondary to RA (for example, vasculitis, pulmonary fibrosis, or Felty
             syndrome). Secondary Sjögren syndrome with RA may be allowed per the discretion of the
             investigator

          -  Diagnosed with juvenile idiopathic arthritis or juvenile RA and/or RA before the age
             of 16 years

          -  Prior or current inflammatory joint disease other than RA (for example, gout, Lyme
             disease, sero-negative spondyloarthropathy, including reactive arthritis, psoriatic
             arthritis, arthropathy of inflammatory bowel disease), or prior or current joint
             infections

          -  Previous history of primary or secondary adrenal insufficiency

        Previous or Concomitant Prohibited Therapy

          -  Treatment with any investigational agent within 4 weeks (or 5 half-lives of the
             investigational drug, whichever is longer) of screening

          -  Previous treatment with any cell-depleting therapies, including investigational agents
             or approved therapies (for example, CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti-CD19,
             anti-CD20)

          -  Treatment with intravenous gamma globulin, plasmapheresis or Prosorba column within 6
             months of screening

          -  Intraarticular (IA) or parenteral glucocorticoids for the treatment of RA within 4
             weeks prior to screening

          -  Previous treatment with glucocorticoids for conditions other than RA, at any dose and
             in any formulation used continuously for >1 week, during the last 1 year prior to
             screening. Topical glucocorticoid creams or ointments for the treatment of skin
             conditions (for example eczema) are allowed

          -  Immunization with a live/attenuated vaccine within 30 days prior to screening.
             Participants must agree not to take live attenuated vaccines (including seasonal nasal
             flu vaccine, varicella vaccine for shingles or chickenpox, vaccines for measles, mumps
             or rubella without or with varicella [MMR or MMRV], oral polio vaccine and vaccines
             for yellow fever), within 30 days before the Screening Visit, throughout the duration
             of the trial and for 60 days following the last dose of study drug

          -  Any previous treatment with alkylating agents such as chlorambucil or with total
             lymphoid irradiation

        Laboratory Exclusion Criteria

          -  Inadequate haematological, renal and liver function

          -  Positive hepatitis B surface antigen or hepatitis C antibody Previous or Concomitant
             Conditions

          -  History of severe allergic or anaphylactic reactions to human, humanized, or murine
             monoclonal antibodies

          -  Evidence of current serious uncontrolled cardiovascular (including uncontrolled
             hyperlipidemia), nervous system, pulmonary (including obstructive pulmonary disease),
             renal, hepatic, endocrine (including uncontrolled diabetes mellitus) or
             gastrointestinal (GI) disease

          -  Current liver disease as determined by the investigator

          -  History of diverticulitis, peptic ulcer disease, diverticulosis requiring antibiotic
             treatment, or chronic ulcerative lower GI disease such as Crohn's disease, ulcerative
             colitis, or other symptomatic lower gastrointestinal conditions that might predispose
             to perforations

          -  Known active current or history of recurrent bacterial, viral, fungal, mycobacterial,
             or other opportunistic infections (including, but not limited to, tuberculosis [TB]
             and atypical mycobacterial disease, hepatitis B and C, Epstein-Barr virus,
             cytomegalovirus and herpes zoster, but excluding fungal infections of nail beds)

          -  Neuropathies or other conditions that might interfere with pain evaluation unless
             related to primary disease under investigation

          -  Any major episode of infection requiring hospitalization or treatment with intravenous
             antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks prior to
             screening

          -  Active TB requiring treatment within the previous 3 years (participants previously
             treated for TB with no recurrence within 3 years are permitted). All Track
             tocilizumab-naïve participants must be screened for latent TB and if positive, should
             be treated following local practice guidelines prior to initiating tocilizumab

          -  History of or currently active, primary or secondary immunodeficiency

          -  Evidence of active malignant disease, malignancies diagnosed within the previous 10
             years (including haematological malignancies and solid tumours, except basal and
             squamous cell carcinoma of the skin or carcinoma in situ of the cervix uteri that was
             excised and cured), or breast cancer diagnosed within the previous 20 years

          -  History of alcohol, drug or chemical abuse within 1 year prior to screening

          -  Pre-existing central nervous system (CNS) demyelination or seizure disorders

          -  Any medical or psychological condition that in the opinion of the principal
             investigator would interfere with safe completion of the trial