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

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.

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.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: Tocilizumab; Drug: TNF-alpha Inhibitor

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 66

Contacts and Locations

Study Locations

• Germany
  • Erlangen, Germany, 91054
    • University Erlangen-Nuremberg, Medical Department 3, Rheumatology & Immunology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients (ages over 18 years) with the diagnosis of RA will be screened for the presence of erosions by Routine procedure with HR-pQCT. In case of a positive scan showing the presence of erosion in the wrist or the MCP Joints and after the decision of the treatment (if either Tocilizumab or TNF-Inhibitor), patients will be enrolled into the study.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Tocilizumab; 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; Patients will be treated with either i.v. Tocilizumab every 4 weeks or s.c. Tocilizumab weekly according to the label; Other Names: RoActemra; Drug: TNF-alpha Inhibitor; Patients will be treated with TNF-Inhibitors either i.v. or s.c. according to the label; Other Names: Adalimumab, Etanercept, Golimumab, Certolizumab-Pegol, Infliximab
TNF-alpha Inhibitor; 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; Patients will be treated with either i.v. Tocilizumab every 4 weeks or s.c. Tocilizumab weekly according to the label; Other Names: RoActemra; Drug: TNF-alpha Inhibitor; Patients will be treated with TNF-Inhibitors either i.v. or s.c. according to the label; Other Names: Adalimumab, Etanercept, Golimumab, Certolizumab-Pegol, Infliximab

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: University of Erlangen-Nürnberg Medical School
• Investigators: Principal Investigator: Georg Schett, Prof. Dr. univ., University of Erlangen-Nuremberg, Medical Department 3

Study record dates

Study Major Dates

• Study Start: October 1, 2015
• Primary Completion (Actual): September 30, 2017
• Study Completion (Actual): March 31, 2018

Study Registration Dates

• First Submitted: May 16, 2016
• First Submitted That Met QC Criteria: May 17, 2016
• First Posted (Estimate): May 20, 2016

Study Record Updates

• Last Update Posted (Actual): September 26, 2019
• Last Update Submitted That Met QC Criteria: September 25, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Necrosis; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Gastrointestinal Agents; Dermatologic Agents; Tumor Necrosis Factor Inhibitors; Etanercept; Adalimumab; Infliximab; Golimumab; Certolizumab Pegol
• Other Study ID Numbers: 1/4