Rheumatoid Arthritis
Conditions
Keywords
Rheumatoid Arthritis
Brief summary
To compare the effects of the combination of ETN and MTX to MTX alone on radiographic change and clinical disease activity in subjects with early RA over 12 months.
Interventions
DRUGEtanercept
Group 1a: Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 1 & 2 Group 1b: Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 1 then Etanercept 50 mg SC injections weekly + Placebo weekly for Period 2 Group 2a: Oral Methotrexate weekly + Placebo for Period 1, then Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 2
DRUGMethotrexate
Group 1a: Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 1 & 2 Group 1b: Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 1 then Etanercept 50 mg SC injections weekly + Placebo weekly for Period 2 Group 2a: Oral Methotrexate weekly + Placebo for Period 1, then Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 2 Group 2b: Oral Methotrexate weekly for both Periods 1 and 2
DRUGPlacebo
Group 1b: Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 1 then Etanercept 50 mg SC injections weekly + Placebo weekly for Period 2 Group 2a: Oral Methotrexate weekly + Placebo for Period 1, then Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 2
Sponsors
Wyeth is now a wholly owned subsidiary of Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Satisfies the 1987 ACR Revised Criteria for Rheumatoid Arthritis * Has RA greater than or equal to 3 months and less than or equal to 2 years
Exclusion criteria
* Received any previous treatment with MTX * Received any previous treatment with ETN or other tumour necrosis factor antagonist
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Participants Achieving Remission As Measured by a Disease Activity Score for 28 Joints (DAS 28) < 2.6. | 12 months | Effects of the combination of etanercept and methotrexate to methotrexate alone on clinical disease activity. DAS28 scale 0 - 10, 3.2 or lower showing controlled disease while 5.1 implies active disease. |
| Year 1 Participants Having an Annualized Modified Total Sharp Score (mTSS) < 0.5. | 12 months | The (van der Heijde) modified total Sharp score (mTSS) is the sum of scores for erosions (range 0-280) and joint space narrowings (range 0-168) and thus has a total range of (0 - 448 ), where zero is the best score , indicating no damage. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety Measured by Number of Participants Reporting a Serious Adverse Event That Led to Death | 12 and 24 months | Safety report for entire trial where participants reported a serious adverse event that led to death. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited worldwide from November 2004 to February 2006.
Pre-assignment details
Participants were randomly assigned equally to 1 of 4 blinded treatment groups: Group (G) 1a received the combination of etanercept (E) and methotrexate (M) in year Y1 and Y2. G1b received the combination of E and M in Y1 and E alone in Y2. G2a received M alone in Y1 and the combination of E and M in Y2. G2b received M alone in Y1 and Y2.
Participants by arm
| Arm | Count |
|---|---|
| Year 1 M+Placebo Oral Methotrexate capsules once weekly + two injections of placebo given at the same time at different sites.
MTX dose is a forced titration from 7.5mg (3 capsules) to 20 mg weekly (8 capsules) by week 8. | 268 |
| Year 1 E+M Etanercept injection- two injections 25 mg weekly (given at the same time at different sites) + oral Methotrexate capsules weekly (same day as injection).
MTX dose is a forced titration from 7.5mg (3 capsules) to 20 mg weekly (8 capsules) by week 8. | 274 |
| Total | 542 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Year 1 | Adverse Event | 0 | 0 | 0 | 0 | 34 | 27 |
| Year 1 | Compliance | 0 | 0 | 0 | 0 | 5 | 1 |
| Year 1 | Lack of Efficacy | 0 | 0 | 0 | 0 | 24 | 9 |
| Year 1 | Lost to Follow-up | 0 | 0 | 0 | 0 | 1 | 0 |
| Year 1 | Missed >4 consecutive doses | 0 | 0 | 0 | 0 | 3 | 2 |
| Year 1 | Physician Decision | 0 | 0 | 0 | 0 | 1 | 0 |
| Year 1 | Protocol deviation | 0 | 0 | 0 | 0 | 2 | 3 |
| Year 1 | Protocol Violation | 0 | 0 | 0 | 0 | 1 | 1 |
| Year 1 | System Toxicity | 0 | 0 | 0 | 0 | 0 | 1 |
| Year 1 | Withdrawal by Subject | 0 | 0 | 0 | 0 | 8 | 9 |
| Year 2 | Adverse Event | 3 | 7 | 5 | 9 | 0 | 0 |
| Year 2 | Compliance | 1 | 0 | 0 | 2 | 0 | 0 |
| Year 2 | Lack of Efficacy | 0 | 1 | 7 | 7 | 0 | 0 |
| Year 2 | Lost to Follow-up | 0 | 0 | 1 | 1 | 0 | 0 |
| Year 2 | Missed >4 consecutive doses | 1 | 1 | 1 | 0 | 0 | 0 |
| Year 2 | Physician Decision | 1 | 1 | 0 | 0 | 0 | 0 |
| Year 2 | Protocol deviation | 0 | 1 | 0 | 0 | 0 | 0 |
| Year 2 | System toxicity | 0 | 0 | 0 | 1 | 0 | 0 |
| Year 2 | Withdrawal by Subject | 1 | 5 | 4 | 3 | 0 | 0 |
Baseline characteristics
| Characteristic | Year 1 M+Placebo | Year 1 E+M | Total |
|---|---|---|---|
| Age Continuous | 51.50 years | 52.50 years | 52.00 years |
| Sex: Female, Male Female | 194 Participants | 204 Participants | 398 Participants |
| Sex: Female, Male Male | 74 Participants | 70 Participants | 144 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 91 / — | 71 / — | 89 / — | 79 / — | 241 / — | 246 / — |
| serious Total, serious adverse events | 8 / — | 11 / — | 10 / — | 12 / — | 34 / — | 33 / — |
Outcome results
Primary
The Number of Participants Achieving Remission As Measured by a Disease Activity Score for 28 Joints (DAS 28) < 2.6.
Effects of the combination of etanercept and methotrexate to methotrexate alone on clinical disease activity. DAS28 scale 0 - 10, 3.2 or lower showing controlled disease while 5.1 implies active disease.
Time frame: 12 months
Population: The analysis population is the modified intent to treat participants from year 1, treatment arms M and E+M.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Year 1 M | The Number of Participants Achieving Remission As Measured by a Disease Activity Score for 28 Joints (DAS 28) < 2.6. | 73 participants |
| Year 1 E+M | The Number of Participants Achieving Remission As Measured by a Disease Activity Score for 28 Joints (DAS 28) < 2.6. | 132 participants |
p-value: <0.001Fisher Exact
Primary
Year 1 Participants Having an Annualized Modified Total Sharp Score (mTSS) < 0.5.
The (van der Heijde) modified total Sharp score (mTSS) is the sum of scores for erosions (range 0-280) and joint space narrowings (range 0-168) and thus has a total range of (0 - 448 ), where zero is the best score , indicating no damage.
Time frame: 12 months
Population: The analysis population is the modified intent to treat participants from year 1, treatment arms M and E+M.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Year 1 M | Year 1 Participants Having an Annualized Modified Total Sharp Score (mTSS) < 0.5. | 135 participants |
| Year 1 E+M | Year 1 Participants Having an Annualized Modified Total Sharp Score (mTSS) < 0.5. | 196 participants |
p-value: <0.001Fisher Exact
Secondary
Safety Measured by Number of Participants Reporting a Serious Adverse Event That Led to Death
Safety report for entire trial where participants reported a serious adverse event that led to death.
Time frame: 12 and 24 months
Population: The analysis population is the modified intent to treat for year 1 (542 overall baseline participants) and year 2 (411 overall baseline participants).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Year 1 M | Safety Measured by Number of Participants Reporting a Serious Adverse Event That Led to Death | 0 participants |
| Year 1 E+M | Safety Measured by Number of Participants Reporting a Serious Adverse Event That Led to Death | 0 participants |
| Year 2 E+M / E | Safety Measured by Number of Participants Reporting a Serious Adverse Event That Led to Death | 0 participants |
| Year 2 M / M | Safety Measured by Number of Participants Reporting a Serious Adverse Event That Led to Death | 1 participants |
| Year 1 M+Placebo | Safety Measured by Number of Participants Reporting a Serious Adverse Event That Led to Death | 0 participants |
| Year 1 E+M | Safety Measured by Number of Participants Reporting a Serious Adverse Event That Led to Death | 1 participants |