Rheumatoid Arthritis
Conditions
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)
Interventions
DRUGETN Alone
etanercept (25 mg, twice/week, s.c.)
DRUGETN+MTX
etanercept (25 mg, twice/week, s.c.) combined with methotrexate (6-8 mg/week)
Sponsors
Japan Biological Agent Study Integrated Consortium
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| EULAR Good Response | 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. |
| ACR50 Response Rate | 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). |
| Radiographic Progression Defined by Change in Van Der Heijde-modified Total Sharp Score | 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. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ETN Alone Etanercept alone treatment group (25mg, twice/week, s.c.) | 74 |
| ETN+MTX Etanercept combined with MTX group (25mg, twice/week, s.c.+MTX 6-8mg/week) | 77 |
| Total | 151 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 1 |
| Overall Study | complex reasons | 11 | 9 |
| Overall Study | Lack of Efficacy | 11 | 1 |
| Overall Study | Withdrawal by Subject | 4 | 2 |
Baseline characteristics
| Characteristic | ETN+MTX | ETN Alone | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 19 Participants | 20 Participants | 39 Participants |
| Age, Categorical Between 18 and 65 years | 58 Participants | 54 Participants | 112 Participants |
| Age, Continuous | 56.6 years STANDARD_DEVIATION 11.1 | 58.1 years STANDARD_DEVIATION 12.6 | 57.3 years STANDARD_DEVIATION 10.2 |
| Region of Enrollment Japan | 77 participants | 74 participants | 151 participants |
| Sex: Female, Male Female | 62 Participants | 65 Participants | 127 Participants |
| Sex: Female, Male Male | 15 Participants | 9 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 34 / 71 | 39 / 76 |
| serious Total, serious adverse events | 2 / 71 | 9 / 76 |
Outcome results
Primary
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).
Time frame: at 24 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ETN Alone | ACR50 Response Rate | 47.8 percentage of responders |
| ETN+MTX | ACR50 Response Rate | 64.4 percentage of responders |
Primary
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.
Time frame: at 24 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ETN Alone | EULAR Good Response | 33.3 percentage of responders |
| ETN+MTX | EULAR Good Response | 52.1 percentage of responders |
Primary
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.
Time frame: at 52 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ETN Alone | Radiographic Progression Defined by Change in Van Der Heijde-modified Total Sharp Score | 3.6 units on a scale | Standard Deviation 10.4 |
| ETN+MTX | Radiographic Progression Defined by Change in Van Der Heijde-modified Total Sharp Score | 0.8 units on a scale | Standard Deviation 6.4 |