Efficacy and Safety of Etanercept in Active RA Despite Methotrexate Therapy in Japan (JESMR)

Efficacy and Safety of Etanercept in Active Rheumatoid Arthritis Despite Methotrexate Therapy in Japan

Multi-center, parallel-group, randomized, open control study. All patients will be selected to two treatment groups.

1. Etanercept alone treatment group (25mg, twice/week, s.c.)
2. Etanercept combined with MTX group (25mg, twice/week, s.c.+MTX 6-8mg/week)

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: ETN Alone; Drug: ETN+MTX

• Study Type: Interventional
• Enrollment (Actual): 151
• Phase: Phase 4

Contacts and Locations

Study Locations

• Japan
  • Tokyo, Japan, 160-8582
    • Keio University

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients had to be at least 18 years of age
• fulfilled the 1987 revised classification criteria for RA by in American College of Rheumatology (ACR)
• met the guidelines for the proper use of ETN in Japan (having at least 6 tender joints and 6 swollen joints
• either serum C-reactive protein more than 2 mg/dl or ESR no less than 28 mm at 1 hour, with adequate safety profiles)
• be ACR functional class I-III
• have been receiving MTX 6 mg/week for a minimum of 3 months at a stable dose for at least 4 weeks at the time of study enrollment

Exclusion Criteria:

• Patients who required concurrent use of prednisone (PSL) >10 mg/day, or its equivalent, were excluded from study entry
• the start of dose increment of PSL equivalents within 3 months of the study enrollment
• experience of antirheumatic therapy except for MTX and PSL equivalents
• previous treatment with ETN or any other biological treatment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: ETN Alone; etanercept (25mg, twice/week, s.c.)	Drug: ETN Alone; etanercept (25 mg, twice/week, s.c.); Other Names: etanercept
Active Comparator: ETN+MTX; etanercept (25mg, twice/week, s.c.) combined with methotrexate (6-8mg/week)	Drug: ETN+MTX; etanercept (25 mg, twice/week, s.c.) combined with methotrexate (6-8 mg/week); Other Names: etanercept and methotrexate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
EULAR Good Response	EULAR good response was defined as reaching, at least, low decease activity by the disease activity score of 28 joints (DAS28) and its improvement by > 1.2. DAS28 is a quantitative composite measure of disease activity for rheumatoid arthritis, and DAS28 < 3.2 is regarded as low disease activity.	at 24 weeks
ACR50 Response Rate	ACR (American College of Rheumatology) 50 response is defined by the following definition of improvement: at least 50% improvement in tender and swollen joint counts and at least 50% improvement in 3 of the 5 remaining ACR-core set measures; patient and physician global assessments, pain, disability, and an acute phase reactant (erythrocyte sedimentation rate or C-reactive protein).	at 24 weeks
Radiographic Progression Defined by Change in Van Der Heijde-modified Total Sharp Score	The van der Heijde-modifiedtotal Sharp score is the sum of scores for erosions and joint space narrowing. The minimum and maximum total scores are 0 and 448, respectively. The maximum number of erosions is 160 in the hands and 120 in the feet; and the maximum scores for joint space narrowing are 120 and 48, respectively. Erosions are scored 1 for a discrete interruption of the cortical surface, and scored 2-5 for a larger defect according to the surface area of the joint involved. Notably, the maximum erosion score in each joint in hands is 5, while it is 10 in the feet. For joint space narrowing, 0=normal; 1=focal or doubtful; 2=general, <50% of the original joint space; 3=general, >50% of the original joint space or subluxation; 4=ankylosis.	at 52 weeks

Collaborators and Investigators

• Sponsor: Japan Biological Agent Study Integrated Consortium
• Investigators: Study Chair: Tsutomu Takeuchi, MD, PhD, JBASIC

Publications and helpful links

General Publications

• Kameda H, Ueki Y, Saito K, Nagaoka S, Hidaka T, Atsumi T, Tsukano M, Kasama T, Shiozawa S, Tanaka Y, Takeuchi T; Japan Biological Agent Study Integrated Consortium. Etanercept (ETN) with methotrexate (MTX) is better than ETN monotherapy in patients with active rheumatoid arthritis despite MTX therapy: a randomized trial. Mod Rheumatol. 2010 Dec;20(6):531-8. doi: 10.1007/s10165-010-0324-4. Epub 2010 Jun 24.
• Kameda H, Kanbe K, Sato E, Ueki Y, Saito K, Nagaoka S, Hidaka T, Atsumi T, Tsukano M, Kasama T, Shiozawa S, Tanaka Y, Yamanaka H, Takeuchi T. Continuation of methotrexate resulted in better clinical and radiographic outcomes than discontinuation upon starting etanercept in patients with rheumatoid arthritis: 52-week results from the JESMR study. J Rheumatol. 2011 Aug;38(8):1585-92. doi: 10.3899/jrheum.110014. Epub 2011 May 15.
• Kameda H, Kanbe K, Sato E, Ueki Y, Saito K, Nagaoka S, Hidaka T, Atsumi T, Tsukano M, Kasama T, Shiozawa S, Tanaka Y, Yamanaka H, Takeuchi T; Japan Biological Agent Integrated Consortium (JBASIC). A merged presentation of clinical and radiographic data using probability plots in a clinical trial, the JESMR study. Ann Rheum Dis. 2013 Feb;72(2):310-2. doi: 10.1136/annrheumdis-2012-201804. Epub 2012 Sep 12. No abstract available.

Study record dates

Study Major Dates

• Study Start: June 1, 2005
• Primary Completion (Actual): October 1, 2008
• Study Completion (Actual): October 1, 2010

Study Registration Dates

• First Submitted: May 25, 2008
• First Submitted That Met QC Criteria: May 30, 2008
• First Posted (Estimate): June 2, 2008

Study Record Updates

• Last Update Posted (Estimate): October 1, 2015
• Last Update Submitted That Met QC Criteria: September 1, 2015
• Last Verified: September 1, 2015

More Information

Terms related to this study

• 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; Peripheral Nervous System Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Gastrointestinal Agents; Dermatologic Agents; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Etanercept; Methotrexate
• Other Study ID Numbers: Etanercept-01