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

• ClinicalTrials.gov Identifier: NCT00688103
• Recruitment Status: Completed
• First Posted: June 2, 2008
• Results First Posted: October 1, 2015
• Last Update Posted: October 1, 2015
• Sponsor: Japan Biological Agent Study Integrated Consortium
• Information provided by (Responsible Party): Hideto Kameda, Japan Biological Agent Study Integrated Consortium

Study Description

Brief Summary:

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)

Condition or disease	Intervention/treatment	Phase
Rheumatoid Arthritis	Drug: ETN Alone; Drug: ETN+MTX	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 151 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Efficacy and Safety of Etanercept in Active Rheumatoid Arthritis Despite Methotrexate Therapy in Japan
• Study Start Date: June 2005
• Actual Primary Completion Date: October 2008
• Actual Study Completion Date: October 2010

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: ETN Alone; etanercept (25mg, twice/week, s.c.)	Drug: ETN Alone; etanercept (25 mg, twice/week, s.c.); Other Name: 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 Name: etanercept and methotrexate

Outcome Measures

Primary Outcome Measures :

1. EULAR Good Response [ Time Frame: at 24 weeks ]
   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.
2. ACR50 Response Rate [ Time Frame: at 24 weeks ]
   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).
3. Radiographic Progression Defined by Change in Van Der Heijde-modified Total Sharp Score [ Time Frame: at 52 weeks ]

   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.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

Japan

Keio University

Tokyo, Japan, 160-8582

Sponsors and Collaborators

Japan Biological Agent Study Integrated Consortium

Investigators

• Study Chair: Tsutomu Takeuchi, MD, PhD; JBASIC

More Information

Publications of Results:

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.

• Responsible Party: Hideto Kameda, Professor, Toho University, Japan Biological Agent Study Integrated Consortium
• ClinicalTrials.gov Identifier: NCT00688103
• Other Study ID Numbers: Etanercept-01
• First Posted: June 2, 2008
• Results First Posted: October 1, 2015
• Last Update Posted: October 1, 2015
• Last Verified: September 2015

Additional relevant MeSH terms:

Arthritis; Arthritis, Rheumatoid; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Etanercept; Methotrexate; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Reproductive Control Agents; Physiological Effects of Drugs; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Dermatologic Agents; Enzyme Inhibitors; Folic Acid Antagonists; Immunosuppressive Agents; Immunologic Factors; Antirheumatic Agents; Nucleic Acid Synthesis Inhibitors; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents