Rheumatoid Arthritis
Conditions
Keywords
subcutaneous tocilizumab, High Resolution peripheral QCT (HR-pQCT), bone erosion, bone microarchitecture, rheumatoid arthritis
Brief summary
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.
Interventions
DRUGsubcutaneous tocilizumab
162 mg subcutaneous, once a week during 12 months
Sponsors
Rennes University Hospital
Centre Hospitalier Régional d'Orléans
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Bone erosion change after 12 months of subcutaneous tocilizumab | baseline and 12 months | changes of width measured by HRpQCT. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Associated factors with erosion changes assessed by HRqQCT | baseline, 3 months, 12 months | Number of participants with associated factors with erosion changes by HRpQCT (Associated therapeutic, clinical and biological response )ultrasound ...) |
| Effect of 12 months of tocilizumab on bone density in the PR | baseline, 12 months | Changes of Bone mineral density by DXA at the lumbar spine and proximal femur |
| Effect of Tocilizumab on synovitis/tenosynovitis assessed by US and agreement with disease activity scores | Predictors baseline, 1 and 3 months of clinical remission and / or ultrasound at 6 and 12 months | 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. |
| Effect of 12 months of tocilizumab on bone microarchitecture in the PR | baseline, 12 months | changes of bone microarchitecture by tibia HRpQCT |
Countries
France
Outcome results
None listed