Comparing the Efficacy of Periarticular Bone Structure in Patients Treated With Either Tocilizumab or Tumor Necrosis Factor Blockers

Study Overview
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Brief Summary
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Comparing the structural effects of TNFi and tocilizumab on the periarticular bone by performing a comprehensive analysis of the periarticular bone changes in RA patients treated with either TNFi or tocilizumab in a longitudinal Setting, using high-resolution peripheral quantitative computed tomography (HR-pQCT), a very sensitive method for visualizing and quantifying bone microstructure in RA patients. Quantitatively assessing the changes of erosions volume, osteophytes size and the area of cortical fenestration in a group of TNFi-treated and a group of tocilizumab- treated RA patients.

Detailed Description
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Inhibition of tumor necrosis factor alpha (TNF-α) and of interleukin- 6 receptor (IL-6R) emerged as highly effective cytokine blocking strategies in the treatment of rheumatoid arthritis (RA) in the last years. Both, inhibition of TNF-α (TNFi) and of the interleukin-6 receptor by tocilizumab ameliorate the signs and symptoms, reverse the elevated acute phase response and inhibit the progression of bone erosion in RA patients (1). Despite striking similarities with respect to their efficacy and safety in the treatment of RA, TNFi and tocilizumab are two entirely distinct approaches for targeting chronic inflammatory diseases in humans. This concept is highlighted by the differential response to TNFi and tocilizumab in other chronic inflammatory diseases such as psoriasis, psoriatic arthritis and spondyloarthritis, with clinical efficacy of the former but not the latter treatment modality (2). On the other hand, tocilizumab has a direct effect on the acute phase response and iron metabolism, which is not found with TNFi. Therefore, subtle differences may exist between TNFi and tocilizumab, which are relevant for the long-term treatment of RA patients.

Official Title
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Non Randomized Parallel-group Clinical Study to Compare the Efficacy of Periarticular Bone Structure in Patients Treated With Either Tocilizumab or Tumor Necrosis Factor Blockers.

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: Tocilizumab
* Drug: TNF-alpha Inhibitor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Females and males with RA erosions in the wrist and/or MCP joints Must be aged ≥ 18 years at time of consent Stable treatment with conventional DMARDs of at least 3 months Exclusion Criteria: Patients exposed to abatacept or rituximab in the last 12 months Patients receiving glucocorticoids over 5 mg prednisolone per day Patients who are younger than 18 years Pregnant or lactating females Patients having received an HR-pQCT examination during the last 6 months before screening

Ages Eligible for Study
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Minimum Age: 18 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Tocilizumab<br>Drug administration of Tocilizumab s.c. or i.v. depending on the preference of the patient and/or physician according to the label | Drug: Tocilizumab<br>* Patients will be treated with either i.v. Tocilizumab every 4 weeks or s.c. Tocilizumab weekly according to the label<br>* Other names: RoActemra;Drug: TNF-alpha Inhibitor<br>* Patients will be treated with TNF-Inhibitors either i.v. or s.c. according to the label<br>* Other names: Adalimumab, Etanercept, Golimumab, Certolizumab-Pegol, Infliximab;|
| TNF-alpha Inhibitor<br>Drug administration s.c. or i.v. of the TNF-Alpha Inhibitor depending on the preference of the patient and/or physician according to the label | Drug: Tocilizumab<br>* Patients will be treated with either i.v. Tocilizumab every 4 weeks or s.c. Tocilizumab weekly according to the label<br>* Other names: RoActemra;Drug: TNF-alpha Inhibitor<br>* Patients will be treated with TNF-Inhibitors either i.v. or s.c. according to the label<br>* Other names: Adalimumab, Etanercept, Golimumab, Certolizumab-Pegol, Infliximab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in erosion volume in the HR-pQCT |  | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the Disease activity score 28 (DAS28) |  | 12months | 
| Change in the Clinical Disease Activity Index (CDAI) |  | 12 months | 
| Changes in the Simple Disease Activity Index (SDAI) |  | 12 months | 
| Change in the Health Assessment Questionnaire (HAQ) |  | 12 months | 
| Number of patients in Remission (DAS28 < 2.6) |  | 12 months | 
| Number of patients in Low Disease Activity (DAS28 ≥ 2.6 und ≤ 3.2) |  | 12 months |