Study of the Response and Cardiorespiratory Endurance in Early RA Patients Treated With Tocilizumab or Methotrexate (TOMERA)

Comparative Study of the Clinical Response and Cardiorespiratory Endurance in Early Rheumatoid Arthritis Patients Treated With Tocilizumab or Methotrexate Addendum Protocol : Global Gene Expression Profiles in Synovial Biopsies

To measure the CRE by a work capacity index obtained in a submaximal testing (W65%/kg) in early RA patients treated with tocilizumab compared to Methotrexate alone.

The secondary endpoints : analyze the clinical efficacy of Tocilizumab in this population and correlate the CRE response with other marker (CRP, Hb, DAS, HAQ) and evaluate the safety profile of Tocilizumab.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: Tocilizumab; Drug: Methotrexate

Detailed Description

Rheumatoid arthritis (RA) is the most prevalent (about 1%) inflammatory rheumatic disorder.

Interleukin-6 (IL-6) has emerged as a potential therapeutic target in RA. This is based on the greater understanding of the role this cytokine can play in various aspects of the pathogenesis of RA. It has been shown that IL-6 is responsible for various clinical symptoms, including,fatigue, anemia, anorexia, fever, as well as the production of autoantibodies and increase in the erythrocyte sedimentation rate, all of which develop in patients with RA. Tocilizumab, as monotherapy and in combination with methotrexate, has been shown to be effective for RA patients with insufficient response to methotrexate or other disease-modifying antirheumatic drugs. These observations about the effects of tocilizumab were extended to patients refractory to tumor necrosis factor inhibitors. Tocilizumab also slows down the progression of structural joint damage. Furthermore, a 5-year long-term safety and efficacy has been shown. The place of Tocilizumab therapy in early RA is still unknown.

Cardiorespiratory endurance (CRE), the most fundamental component of physical fitness can be severely impaired in patients with rheumatoid arthritis (RA). It has been shown that intensive and early treatment of RA can induce sustained clinical remission, improve general health and physical fitness and might therefore have an impact on the quality of life of RA patient. This study was planned to measure the CRE by a work capacity index obtained in a submaximal testing (W65%/kg) in early RA patients treated with tocilizumab compared to Methotrexate alone.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles, Belgium, 1200
    • Université Catholique de Louvain

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of RA (according to American College of Rheumatology ACR criteria)
• Disease duration < 2 years.
• Age between 18 and 70 years old.
• Active RA defined by a disease activity score 28 DAS28-CRP score > 3.2 with a swollen joint count ≥ 4
• MTX naive
• Stable therapy with corticosteroids or nonsteroidal anti-inflammatory drug NSAIDs
• Presence of knee arthralgia or synovitis (addendum protocol with synovial biopsy).

Exclusion Criteria:

Previous MTX treatment. Exclusion for severe physical handicap to perform CRE. Exclusion for general safety (history of severe allergic reaction, sepsis, malignancy within 5 years, pregnancy, severe heart failure) Concurrent treatment with other DMARDs than MTX or any anti-TNF and biological therapies.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tocilizumab; Tocilizumab (8 mg/kg monthly from week 0 to 20)	Drug: Tocilizumab; Tocilizumab (8 mg/kg monthly from week 0 to 20); Other Names: Roche EU/1/08/492/001; ATC code L04AC07
Active Comparator: Methotrexate; MTX at a dose ranging from 10 mg/week at baseline to 20 mg/week at week 8	Drug: Methotrexate; MTX at a dose ranging from 10 mg/week at baseline to 20 mg/week at week 8

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To measure the CRE by a work capacity index obtained in a submaximal testing (W65%/kg) in early RA patients treated with tocilizumab compared to Methotrexate alone.	not necessary	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To analyze the clinical efficacy of Tocilizumab in this population.	no necessary	2 years
To correlate the CRE response with other marker (CRP, Hb, Disease activity score DAS, HAQ).	no necessary	2 years
To evaluate the safety profile of Tocilizumab.	no necessary	2 years
To assess the effect of Tocilizumab on synovial histopathology of early RA	not necessary	2 years

Collaborators and Investigators

• Sponsor: Patrick Durez
• Investigators: Principal Investigator: Patrick Durez, MD, Université Catholique de Louvain

Study record dates

Study Major Dates

• Study Start: May 1, 2010
• Primary Completion (Actual): June 1, 2013
• Study Completion (Actual): June 1, 2013

Study Registration Dates

• First Submitted: November 19, 2010
• First Submitted That Met QC Criteria: November 19, 2010
• First Posted (Estimate): November 22, 2010

Study Record Updates

• Last Update Posted (Estimate): October 31, 2013
• Last Update Submitted That Met QC Criteria: October 30, 2013
• Last Verified: October 1, 2013

More Information

Terms related to this study

• Keywords: Tocilizumab; Rheumatoid arthritis; Cardiorespiratory endurance
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Methotrexate
• Other Study ID Numbers: P1200/002