Tocilizumab Effect iN pOlymyalgia Rheumatica

Study Overview
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Brief Summary
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Phase 1: Patients are treated with infusions of Tocilizumab (TCZ) for 3 months. Clinical evaluation is performed using PMR-AS. The PMR-AS is computed by summing the 5 variables after multiplying by 0.1 for weighting purposes: PMR-AS (activity scale = AS) = C reactive protein (CRP) (mg/dl) + patient scale (VASp) (0-10 scale) + physician scale (VASph) (0-10 scale) + morning stiffness(MST) [min]×0.1) + elevation of upper limbs (EUL) (0-3 scale). At the end of the phase 1,the patients stop TCZ and entered in phase 2 at week 12. Phase 2: All the patients are included in the phase 2 and treated with glucocorticoid (GC)for 3 months. Two arms are possible according to the PMR-AS. Either the classical GC treatment (0.3mg/kg), either a low dose group of GC(0.15mg/kg) .

Official Title
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Phase II Open 24 Weeks Study to Evaluate Effect and Safety of Tocilizumab as the First Line Therapy in Subjects With Polymyalgia Rheumatica (PMR)

Conditions
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Polymyalgia Rheumatica

Intervention / Treatment
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* Drug: TCZ


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 50 years and 75 years included PMR-AS > 10 PMR according to the Chuang criteria Evolving since less than 12 months Without Horton disease Able to understand and accept the study Agree to sign the inform consent form Without GC, or at least during 1 month and stop since 7 days before the inclusion. Stable dose of Nonsteroidal anti-inflammatory since 4 weeks before the inclusion. Birth controlled during all the study and 6 months after Exclusion Criteria: Disagree to participated Unable to understand the study Participation to an other study in the 3 months before the inclusion Treated by GC at 0.3mg/kg/d in the past 7 days Less than 50 years old or more than 75 years old Uncontrolled dyslipidemia, high blood pressure or cardiovascular disease Histories of important allergy Historically positive test or test positive at screening for HIV-1 antibody, hepatitis B surface antigen, or hepatitis C antibody. Abnormal screening blood test : leukocyte count less than 3.5 × 109 cells/L, neutrophil count less than 2 × 109 cells/L, hemoglobin level less than 85 g/L, platelet count less than 100 × 109 cells/L, or hepatic aminotransferase or alkaline phosphatase levels greater than 3 times the upper limit of normal Other inflammatory rheumatic disease or connective disease Clinical evidence of significant unstable or uncontrolled acute or chronic diseases not due to PMR (eg. Cardiovascular, pulmonary, hematologic, gastrointestinal, hepatic, renal, neurological, malignancy or infectious diseases) Current drug or alcohol abuse Patients treated with an immunosuppressive agents in the past 4 weeks Live/attenuated vaccine in the past 4 weeks Clinical symptoms of giant cell arteritis History of infection or infestation in the past 3 months Active tuberculosis Planned surgical procedure History of malignant neoplasm within the last 5 years, except for adequately treated cancer of the skin (basal or squamous cell) History or current tumoral hematological disease Severe allergic or anaphylactic reactions about one of the TCZ component Pregnant women during the study and six month after the end of the study Breast feeding mother Dysthyroidia Unstable treatment by statin in the past 3 months Parkinson disease Fibromyalgia Peripheric arthritis Articular chondrocalcinosis or hydorxyapatites rhumatisms

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TCZ<br>Tocilizumab at week 0, week 4 and week 8 8mg/kg at each perfusion | Drug: TCZ<br>* Tocilizumab at week 0, 4 and 8.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy at W12 | PMR-AS at week 12 | 12 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and efficacy during the study | To maintain low disease activity (PMR-AS) in the low corticosteroid dose group from W12 to W24 On the inflammatory changes (synovitis, myositis, tenosynovitis aund bursitis) between baseline, W2 and 12 visualize by ultrasonography, MRI and Tep-Scan. On sparing corticosteroid, with the comparison of the cumulative corticosteroid dosage beetwen the two groups of patients in the phase 2, W12 to 24. On the circulating serum cytokines and immunoregulators (IL-6, IL-1, BLyS/BAFF, IL-6 receptor, gp130) and B cells receptors and on the phenotype of circulating T- and B-cells between baseline and W4 and 12 On inflammatory parameters (CRP and ESR) between baseline and W 2,4,8,12,16,20 and 24 On the quality of life of patients between baseline and W 4,12,16, 20 and 24 To evaluate the side-effects in relation to the use of Tocilizumab treatment. [ Time Frame: After first, second and third treatment and during follow up ] | Week 2,4,8,12,16,20 and 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Polymyalgia Rheumatica, Glucocorticotherapy, PMR-AS, Tocilizumab