Filling Bone Erosions: a Longitudinal Multicentric HR-pQCT Study of Subcutaneous Tocilizumab in Rheumatoid Arthritis

Study Overview
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Brief Summary
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Rheumatoid arthritis (RA) is a chronic inflammatory disease mediated by the production of several cytokines, which leads to the destruction of bone and cartilage tissue in multiple joints and to bone loss. Conventional radiographs (CR) are considered as the gold standard for diagnosis and follow up of joint changes in RA. But this method has low sensitivity to detect early erosive changes and is unable to evaluate periarticular bone loss. High Resolution peripheral QCT (HRpQCT) enables the detection of erosions less than 0.5 mm in width or depth at metacarpo-phalangeal (MCP) joints. Using 3-D high resolution analysis of cortical bone erosions, this one is also able to evaluate the volumes of erosion and the evolution under treatments IL6 (6- interleukin) plays a major role in inflammatory process and bone damages related to RA. Tocilizumab (TCZ) is a humanized anti-IL-6R monoclonal antibody, developed and investigated in several clinical trials in RA. This biotherapy, in association with methotrexate (MTX) or given in monotherapy, is efficient in RA with inadequate response to MTX or anti-TNF b (tumor necrosis factor). TCZ reduces dramatically systemic inflammation, structural progression and improves clinical symptoms and quality of life. Tocilizumab may help reducing bone erosions, periarticular osteopenia and systemic bone loss.

Official Title
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Filling Bone Erosions: a Longitudinal Multicentric HR-pQCT Study of 12 Months Subcutaneous Tocilizumab in Rheumatoid Arthritis Phase IV Prospective Multicentrique Study

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: subcutaneous tocilizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Active RA, < 10 years disease duration, diagnosed according to the ACR-EULAR 2010 classification criteria DAS 28 superior or equal to 3.2 despite DMARD or biological treatment (other than tocilizumab) Superior or equal to one joint erosion at the right or left MCP 2, 3 on X-rays Oral corticosteroid ≤ 10 mg/day prednisone or equivalent stable for at least one month RA patients eligible to subcutaneous Tocilizumab monotherapy Exclusion Criteria: Treatment with zoledronic acid or denosumab (less than one year) Intra-articular injection of corticosteroids at the MCP in the previous three months Tocilizumab contra-indications in accordance with SPC (Summary of Product Characteristics) :Hypersensitivity to the active substance or to any of the excipients Active, severe infections including active tuberculosis Diverticulitis Active hepatic disease and hepatic Impairment including viral hepatitis Elevated Alanine Aminotransferase or Aspartate Aminotransferase >5×ULN Absolute neutrophil count < 0.5 × 10 exp 9 /L Platelet count < 50×10 exp 3 /μL, General: Absence of informed consent Prior or planned joint surgery of the hands which might impact the interpretation of imaging assessments.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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: Roactemra<br>subcutaneous tocilizumab | Drug: subcutaneous tocilizumab<br>* 162 mg subcutaneous, once a week during 12 months<br>* Other names: Roactemra;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bone erosion change after 12 months of subcutaneous tocilizumab | changes of width measured by HRpQCT. | baseline and 12 months | 
| Bone erosion change after 12 months of subcutaneous tocilizumab | changes of depth measured by HRpQCT. | baseline and 12 months | 
| Bone erosion change after 12 months of subcutaneous tocilizumab | changes of volume measured by HRpQCT. | baseline and 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Associated factors with erosion changes assessed by HRqQCT | Number of participants with associated factors with erosion changes by HRpQCT (Associated therapeutic, clinical and biological response )ultrasound ...) | baseline, 3 months, 12 months | 
| Effect of 12 months of tocilizumab on bone density in the PR | Changes of Bone mineral density by DXA at the lumbar spine and proximal femur | baseline, 12 months | 
| Effect of Tocilizumab on synovitis/tenosynovitis assessed by US and agreement with disease activity scores | Correlation Between clinical activity measured by various indices (Disease Activity Score 28, Clinical Disease Activity Iindex , Simplify Disease Activity Index , American College of Rheumatology - European League against Rheumatism: ACR EULAR) and ultrasound data. | Predictors baseline, 1 and 3 months of clinical remission and / or ultrasound at 6 and 12 months | 
| Effect of 12 months of tocilizumab on bone microarchitecture in the PR | changes of bone microarchitecture by tibia HRpQCT | baseline, 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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subcutaneous tocilizumab, High Resolution peripheral QCT (HR-pQCT), bone erosion, bone microarchitecture, rheumatoid arthritis