Efficacy and Safety of Etanercept in Active RA Despite Methotrexate Therapy in Japan (JESMR)
Primary Purpose
Rheumatoid Arthritis
Status
Completed
Phase
Phase 4
Locations
Japan
Study Type
Interventional
Intervention
ETN Alone
ETN+MTX
Sponsored by
About this trial
This is an interventional treatment trial for Rheumatoid Arthritis
Eligibility 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
Sites / Locations
- Keio University
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
ETN Alone
ETN+MTX
Arm Description
etanercept (25mg, twice/week, s.c.)
etanercept (25mg, twice/week, s.c.) combined with methotrexate (6-8mg/week)
Outcomes
Primary Outcome Measures
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.
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).
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.
Secondary Outcome Measures
Full Information
NCT ID
NCT00688103
First Posted
May 25, 2008
Last Updated
September 1, 2015
Sponsor
Japan Biological Agent Study Integrated Consortium
1. Study Identification
Unique Protocol Identification Number
NCT00688103
Brief Title
Efficacy and Safety of Etanercept in Active RA Despite Methotrexate Therapy in Japan
Acronym
JESMR
Official Title
Efficacy and Safety of Etanercept in Active Rheumatoid Arthritis Despite Methotrexate Therapy in Japan
Study Type
Interventional
2. Study Status
Record Verification Date
September 2015
Overall Recruitment Status
Completed
Study Start Date
June 2005 (undefined)
Primary Completion Date
October 2008 (Actual)
Study Completion Date
October 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Japan Biological Agent Study Integrated Consortium
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Multi-center, parallel-group, randomized, open control study. All patients will be selected to two treatment groups.
Etanercept alone treatment group (25mg, twice/week, s.c.)
Etanercept combined with MTX group (25mg, twice/week, s.c.+MTX 6-8mg/week)
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
151 (Actual)
8. Arms, Groups, and Interventions
Arm Title
ETN Alone
Arm Type
Active Comparator
Arm Description
etanercept (25mg, twice/week, s.c.)
Arm Title
ETN+MTX
Arm Type
Active Comparator
Arm Description
etanercept (25mg, twice/week, s.c.) combined with methotrexate (6-8mg/week)
Intervention Type
Drug
Intervention Name(s)
ETN Alone
Other Intervention Name(s)
etanercept
Intervention Description
etanercept (25 mg, twice/week, s.c.)
Intervention Type
Drug
Intervention Name(s)
ETN+MTX
Other Intervention Name(s)
etanercept and methotrexate
Intervention Description
etanercept (25 mg, twice/week, s.c.) combined with methotrexate (6-8 mg/week)
Primary Outcome Measure Information:
Title
EULAR Good Response
Description
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.
Time Frame
at 24 weeks
Title
ACR50 Response Rate
Description
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).
Time Frame
at 24 weeks
Title
Radiographic Progression Defined by Change in Van Der Heijde-modified Total Sharp Score
Description
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.
Time Frame
at 52 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tsutomu Takeuchi, MD, PhD
Organizational Affiliation
JBASIC
Official's Role
Study Chair
Facility Information:
Facility Name
Keio University
City
Tokyo
ZIP/Postal Code
160-8582
Country
Japan
12. IPD Sharing Statement
Citations:
PubMed Identifier
20574649
Citation
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.
Results Reference
result
PubMed Identifier
21572151
Citation
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.
Results Reference
result
PubMed Identifier
22975754
Citation
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.
Results Reference
result
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Efficacy and Safety of Etanercept in Active RA Despite Methotrexate Therapy in Japan
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