Trial Outcomes & Findings for Study Comparing Etanercept and Methotrexate vs. Methotrexate Alone in Rheumatoid Arthritis (NCT NCT00195494)
NCT ID: NCT00195494
Last Updated: 2012-09-05
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
542 participants
Primary outcome timeframe
12 months
Results posted on
2012-09-05
Participant Flow
Participants were recruited worldwide from November 2004 to February 2006.
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.
Participant milestones
| Measure |
Year 1 E+M / Year 2 E+M
Following a blinded transition from year one- Etanercept injection- two injections 25 mg weekly (given at the same time at different sites)+ oral Methotrexate capsules weekly (same day as injection).
Dose consistent with the ending dose at year one (usually 20 mgs). No reduction of MTX dose is permitted in year two.
|
Year 1 M / Year 2 E+M
Following a blinded transition from year one- Etanercept two injections 25 mg weekly (given at the same time at different sites) + oral Methotrexate capsules weekly (same day as injection).
Dose consistent with the ending dose at year one (usually 20 mgs). No reduction of MTX dose is permitted in year two.
|
Year 1 E+M / Year 2 E
Following a blinded transition from year one-Etanercept two injections 25 mg weekly (given at the same time at different sites).
|
Year 1 M / Year 2 M
Following a blinded transition from year one- Methotrexate dose consistent with the ending dose of year one (usually 20 mgs).
No reduction of MTX dose is permitted in year two.
|
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.
|
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.
|
|---|---|---|---|---|---|---|
|
Year 1
STARTED
|
0
|
0
|
0
|
0
|
268
|
274
|
|
Year 1
COMPLETED
|
0
|
0
|
0
|
0
|
189
|
221
|
|
Year 1
NOT COMPLETED
|
0
|
0
|
0
|
0
|
79
|
53
|
|
Year 2
STARTED
|
111
|
90
|
111
|
99
|
0
|
0
|
|
Year 2
COMPLETED
|
104
|
74
|
93
|
76
|
0
|
0
|
|
Year 2
NOT COMPLETED
|
7
|
16
|
18
|
23
|
0
|
0
|
Reasons for withdrawal
| Measure |
Year 1 E+M / Year 2 E+M
Following a blinded transition from year one- Etanercept injection- two injections 25 mg weekly (given at the same time at different sites)+ oral Methotrexate capsules weekly (same day as injection).
Dose consistent with the ending dose at year one (usually 20 mgs). No reduction of MTX dose is permitted in year two.
|
Year 1 M / Year 2 E+M
Following a blinded transition from year one- Etanercept two injections 25 mg weekly (given at the same time at different sites) + oral Methotrexate capsules weekly (same day as injection).
Dose consistent with the ending dose at year one (usually 20 mgs). No reduction of MTX dose is permitted in year two.
|
Year 1 E+M / Year 2 E
Following a blinded transition from year one-Etanercept two injections 25 mg weekly (given at the same time at different sites).
|
Year 1 M / Year 2 M
Following a blinded transition from year one- Methotrexate dose consistent with the ending dose of year one (usually 20 mgs).
No reduction of MTX dose is permitted in year two.
|
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.
|
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.
|
|---|---|---|---|---|---|---|
|
Year 1
Adverse Event
|
0
|
0
|
0
|
0
|
34
|
27
|
|
Year 1
System Toxicity
|
0
|
0
|
0
|
0
|
0
|
1
|
|
Year 1
Lack of Efficacy
|
0
|
0
|
0
|
0
|
24
|
9
|
|
Year 1
Compliance
|
0
|
0
|
0
|
0
|
5
|
1
|
|
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
Protocol deviation
|
0
|
0
|
0
|
0
|
2
|
3
|
|
Year 1
Physician Decision
|
0
|
0
|
0
|
0
|
1
|
0
|
|
Year 1
Withdrawal by Subject
|
0
|
0
|
0
|
0
|
8
|
9
|
|
Year 1
Protocol Violation
|
0
|
0
|
0
|
0
|
1
|
1
|
|
Year 2
Adverse Event
|
3
|
7
|
5
|
9
|
0
|
0
|
|
Year 2
Lack of Efficacy
|
0
|
1
|
7
|
7
|
0
|
0
|
|
Year 2
Compliance
|
1
|
0
|
0
|
2
|
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
Protocol deviation
|
0
|
1
|
0
|
0
|
0
|
0
|
|
Year 2
Physician Decision
|
1
|
1
|
0
|
0
|
0
|
0
|
|
Year 2
Withdrawal by Subject
|
1
|
5
|
4
|
3
|
0
|
0
|
|
Year 2
System toxicity
|
0
|
0
|
0
|
1
|
0
|
0
|
Baseline Characteristics
Study Comparing Etanercept and Methotrexate vs. Methotrexate Alone in Rheumatoid Arthritis
Baseline characteristics by cohort
| Measure |
Year 1 M+Placebo
n=268 Participants
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.
|
Year 1 E+M
n=274 Participants
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.
|
Total
n=542 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
51.50 years
n=5 Participants
|
52.50 years
n=7 Participants
|
52.00 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
194 Participants
n=5 Participants
|
204 Participants
n=7 Participants
|
398 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
74 Participants
n=5 Participants
|
70 Participants
n=7 Participants
|
144 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 12 monthsPopulation: The analysis population is the modified intent to treat participants from year 1, treatment arms M and E+M.
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.
Outcome measures
| Measure |
Year 1 M
n=263 Participants
Oral methotrexate capsules 7.5mg weekly and etanercept placebo at the same day and time.
|
Year 1 E+M
n=265 Participants
etanercept injection 50mg once weekly and oral methotrexate capsules 7.5 mg once weekly at the same time
|
Year 2 E+M / E
Following a blinded transition from year one-Etanercept two injections 25 mg weekly (given at the same time at different sites).
|
Year 2 M / M
Following a blinded transition from year one- MTX dose consistent with the ending dose of year one (usually 20 mgs).
No reduction of MTX dose is permitted in year two.
|
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.
|
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.
|
|---|---|---|---|---|---|---|
|
The Number of Participants Achieving Remission As Measured by a Disease Activity Score for 28 Joints (DAS 28) < 2.6.
|
73 participants
|
132 participants
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: 12 monthsPopulation: The analysis population is the modified intent to treat participants from year 1, treatment arms M and E+M.
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.
Outcome measures
| Measure |
Year 1 M
n=230 Participants
Oral methotrexate capsules 7.5mg weekly and etanercept placebo at the same day and time.
|
Year 1 E+M
n=246 Participants
etanercept injection 50mg once weekly and oral methotrexate capsules 7.5 mg once weekly at the same time
|
Year 2 E+M / E
Following a blinded transition from year one-Etanercept two injections 25 mg weekly (given at the same time at different sites).
|
Year 2 M / M
Following a blinded transition from year one- MTX dose consistent with the ending dose of year one (usually 20 mgs).
No reduction of MTX dose is permitted in year two.
|
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.
|
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.
|
|---|---|---|---|---|---|---|
|
Year 1 Participants Having an Annualized Modified Total Sharp Score (mTSS) < 0.5.
|
135 participants
|
196 participants
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 12 and 24 monthsPopulation: The analysis population is the modified intent to treat for year 1 (542 overall baseline participants) and year 2 (411 overall baseline participants).
Safety report for entire trial where participants reported a serious adverse event that led to death.
Outcome measures
| Measure |
Year 1 M
n=111 Participants
Oral methotrexate capsules 7.5mg weekly and etanercept placebo at the same day and time.
|
Year 1 E+M
n=90 Participants
etanercept injection 50mg once weekly and oral methotrexate capsules 7.5 mg once weekly at the same time
|
Year 2 E+M / E
n=111 Participants
Following a blinded transition from year one-Etanercept two injections 25 mg weekly (given at the same time at different sites).
|
Year 2 M / M
n=99 Participants
Following a blinded transition from year one- MTX dose consistent with the ending dose of year one (usually 20 mgs).
No reduction of MTX dose is permitted in year two.
|
Year 1 M+Placebo
n=268 Participants
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.
|
Year 1 E+M
n=274 Participants
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.
|
|---|---|---|---|---|---|---|
|
Safety Measured by Number of Participants Reporting a Serious Adverse Event That Led to Death
|
0 participants
|
0 participants
|
0 participants
|
1 participants
|
0 participants
|
1 participants
|
Adverse Events
Year 1 E+M / Year 2 E+M
Serious events: 8 serious events
Other events: 91 other events
Deaths: 0 deaths
Year 1 M / Year 2 E+M
Serious events: 11 serious events
Other events: 71 other events
Deaths: 0 deaths
Year 1 E+M / Year 2 E
Serious events: 10 serious events
Other events: 89 other events
Deaths: 0 deaths
Year 1 M / Year 2 M
Serious events: 12 serious events
Other events: 79 other events
Deaths: 0 deaths
Year 1 M+Placebo
Serious events: 34 serious events
Other events: 241 other events
Deaths: 0 deaths
Year 1 E+M
Serious events: 33 serious events
Other events: 246 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Year 1 E+M / Year 2 E+M
Following a blinded transition from year one- Etanercept injection- two injections 25 mg weekly (given at the same time at different sites)+ oral Methotrexate capsules weekly (same day as injection).
Dose consistent with the ending dose at year one (usually 20 mgs). No reduction of MTX dose is permitted in year two.
|
Year 1 M / Year 2 E+M
Following a blinded transition from year one- Etanercept two injections 25 mg weekly (given at the same time at different sites) + oral Methotrexate capsules weekly (same day as injection).
Dose consistent with the ending dose at year one (usually 20 mgs). No reduction of MTX dose is permitted in year two.
|
Year 1 E+M / Year 2 E
Following a blinded transition from year one-Etanercept two injections 25 mg weekly (given at the same time at different sites).
|
Year 1 M / Year 2 M
Following a blinded transition from year one- Methotrexate dose consistent with the ending dose of year one (usually 20 mgs).
No reduction of MTX dose is permitted in year two.
|
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.
|
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.
|
|---|---|---|---|---|---|---|
|
Cardiac disorders
Angina unstable
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
0.00%
0/268
|
0.36%
1/274
|
|
Cardiac disorders
Arrhythmia
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
0.00%
0/268
|
0.36%
1/274
|
|
Cardiac disorders
Aterial fibrillation
|
0.00%
0/111
|
1.1%
1/90
|
0.00%
0/111
|
0.00%
0/99
|
0.37%
1/268
|
0.00%
0/274
|
|
Cardiac disorders
Myocardial infarction
|
0.00%
0/111
|
1.1%
1/90
|
0.00%
0/111
|
0.00%
0/99
|
0.37%
1/268
|
0.00%
0/274
|
|
Cardiac disorders
Pericarditis
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
0.00%
0/268
|
0.36%
1/274
|
|
Cardiac disorders
Ventricular tachycardia
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
0.37%
1/268
|
0.00%
0/274
|
|
Ear and labyrinth disorders
Vertigo
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
0.00%
0/268
|
0.36%
1/274
|
|
Eye disorders
Photophobia
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
0.37%
1/268
|
0.00%
0/274
|
|
Gastrointestinal disorders
Appendicitis perforated
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
0.37%
1/268
|
0.00%
0/274
|
|
Gastrointestinal disorders
Gastritis
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
1.0%
1/99
|
0.00%
0/268
|
0.36%
1/274
|
|
Gastrointestinal disorders
General gastrointestinal disorder
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
0.37%
1/268
|
0.00%
0/274
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.00%
0/111
|
1.1%
1/90
|
0.00%
0/111
|
0.00%
0/99
|
0.37%
1/268
|
0.00%
0/274
|
|
Gastrointestinal disorders
Mechanical ileus
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
0.37%
1/268
|
0.00%
0/274
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
0.37%
1/268
|
0.00%
0/274
|
|
General disorders
Chest pain
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
0.37%
1/268
|
0.36%
1/274
|
|
General disorders
General physical health deterioration
|
0.00%
0/111
|
0.00%
0/90
|
0.90%
1/111
|
0.00%
0/99
|
0.00%
0/268
|
0.36%
1/274
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
0.00%
0/268
|
0.73%
2/274
|
|
Hepatobiliary disorders
Gallbladder disorder
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
0.00%
0/268
|
0.36%
1/274
|
|
Infections and infestations
Acute sinusitis
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
1.0%
1/99
|
0.37%
1/268
|
0.00%
0/274
|
|
Infections and infestations
Bronchitis
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
0.37%
1/268
|
0.00%
0/274
|
|
Infections and infestations
Chronic sinusitis
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
0.37%
1/268
|
0.00%
0/274
|
|
Infections and infestations
Diverticulitis
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
0.37%
1/268
|
0.00%
0/274
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
0.37%
1/268
|
0.00%
0/274
|
|
Infections and infestations
Herpes zoster
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
0.37%
1/268
|
0.00%
0/274
|
|
Infections and infestations
Lung infection
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
0.00%
0/268
|
0.36%
1/274
|
|
Infections and infestations
Lyme disease
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
0.00%
0/268
|
0.36%
1/274
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
0.00%
0/268
|
0.36%
1/274
|
|
Infections and infestations
Pneumonia
|
0.00%
0/111
|
1.1%
1/90
|
0.00%
0/111
|
1.0%
1/99
|
0.37%
1/268
|
0.36%
1/274
|
|
Infections and infestations
Septic athritis staphylococcal
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
0.00%
0/268
|
0.36%
1/274
|
|
Infections and infestations
Skin infection
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
0.37%
1/268
|
0.00%
0/274
|
|
Infections and infestations
Streptococcal infection
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
0.00%
0/268
|
0.36%
1/274
|
|
Injury, poisoning and procedural complications
Accidental overdose
|
1.8%
2/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
0.37%
1/268
|
0.00%
0/274
|
|
Injury, poisoning and procedural complications
Joint injury
|
0.90%
1/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
0.00%
0/268
|
0.36%
1/274
|
|
Injury, poisoning and procedural complications
Overdose
|
0.90%
1/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
0.00%
0/268
|
0.36%
1/274
|
|
Injury, poisoning and procedural complications
Pelvic fracture
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
0.37%
1/268
|
0.00%
0/274
|
|
Injury, poisoning and procedural complications
Procedural pain
|
0.00%
0/111
|
1.1%
1/90
|
0.00%
0/111
|
0.00%
0/99
|
0.37%
1/268
|
0.00%
0/274
|
|
Injury, poisoning and procedural complications
Radius fracture
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
0.00%
0/268
|
0.36%
1/274
|
|
Injury, poisoning and procedural complications
Spinal fracture
|
0.00%
0/111
|
0.00%
0/90
|
0.90%
1/111
|
0.00%
0/99
|
0.37%
1/268
|
0.00%
0/274
|
|
Investigations
Blood alkaline phosphatase increased
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
0.37%
1/268
|
0.00%
0/274
|
|
Investigations
Hepatic enzyme increased
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
0.00%
0/268
|
0.36%
1/274
|
|
Investigations
Transaminases increased
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
0.37%
1/268
|
0.00%
0/274
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
0.00%
0/268
|
0.36%
1/274
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
0.00%
0/268
|
0.36%
1/274
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
0.37%
1/268
|
0.00%
0/274
|
|
Musculoskeletal and connective tissue disorders
Haemarthrosis
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
0.37%
1/268
|
0.00%
0/274
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc disorder
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
0.00%
0/268
|
0.36%
1/274
|
|
Musculoskeletal and connective tissue disorders
Intervetebral disc protrusion
|
0.90%
1/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
0.00%
0/268
|
0.73%
2/274
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
0.75%
2/268
|
0.00%
0/274
|
|
Musculoskeletal and connective tissue disorders
Rheumatoid arthritis
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
1.0%
1/99
|
1.9%
5/268
|
0.73%
2/274
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
|
0.00%
0/111
|
1.1%
1/90
|
0.90%
1/111
|
1.0%
1/99
|
0.37%
1/268
|
0.00%
0/274
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bowen's disease
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
0.00%
0/268
|
0.36%
1/274
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
1.1%
3/268
|
0.00%
0/274
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Chronic lymphocytic leukamia
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
0.00%
0/268
|
0.36%
1/274
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer
|
0.00%
0/111
|
1.1%
1/90
|
0.00%
0/111
|
0.00%
0/99
|
0.00%
0/268
|
0.36%
1/274
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tongue neoplasm
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
0.00%
0/268
|
0.36%
1/274
|
|
Nervous system disorders
Cerebral haemorrhage
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
0.00%
0/268
|
0.36%
1/274
|
|
Nervous system disorders
Headache
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
0.37%
1/268
|
0.00%
0/274
|
|
Nervous system disorders
Paraesthesia
|
0.00%
0/111
|
0.00%
0/90
|
0.90%
1/111
|
0.00%
0/99
|
0.00%
0/268
|
0.36%
1/274
|
|
Nervous system disorders
Syncope
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
0.00%
0/268
|
0.36%
1/274
|
|
Nervous system disorders
Syncope vasovagal
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
0.00%
0/268
|
0.36%
1/274
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
0.37%
1/268
|
0.00%
0/274
|
|
Psychiatric disorders
Sleep disorder
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
0.00%
0/268
|
0.36%
1/274
|
|
Renal and urinary disorders
Renal failure
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
0.00%
0/268
|
0.36%
1/274
|
|
Renal and urinary disorders
Urinary retention
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
0.37%
1/268
|
0.00%
0/274
|
|
Respiratory, thoracic and mediastinal disorders
Idiopathic pulmonary fibrosis
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
0.37%
1/268
|
0.00%
0/274
|
|
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
0.00%
0/268
|
0.73%
2/274
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
0.00%
0/268
|
0.36%
1/274
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
0.37%
1/268
|
0.00%
0/274
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
0.00%
0/268
|
0.36%
1/274
|
|
Surgical and medical procedures
Hip arthroplasty
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
0.75%
2/268
|
0.00%
0/274
|
|
Surgical and medical procedures
Hospitalisation
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
0.00%
0/268
|
0.36%
1/274
|
|
Vascular disorders
Deep vein thrombosis
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
0.37%
1/268
|
0.00%
0/274
|
|
Vascular disorders
Infarction
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
0.00%
0/268
|
0.36%
1/274
|
|
Vascular disorders
Ischaemia
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
0.37%
1/268
|
0.00%
0/274
|
|
Cardiac disorders
Aortic valve stenosis
|
0.00%
0/111
|
1.1%
1/90
|
0.00%
0/111
|
0.00%
0/99
|
0.00%
0/268
|
0.00%
0/274
|
|
Cardiac disorders
Atrio ventricular block
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
1.0%
1/99
|
0.00%
0/268
|
0.00%
0/274
|
|
Cardiac disorders
Mitral valve incompetence
|
0.00%
0/111
|
1.1%
1/90
|
0.00%
0/111
|
0.00%
0/99
|
0.00%
0/268
|
0.00%
0/274
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
1.0%
1/99
|
0.00%
0/268
|
0.00%
0/274
|
|
Gastrointestinal disorders
Inguinal hernia
|
0.00%
0/111
|
0.00%
0/90
|
0.90%
1/111
|
0.00%
0/99
|
0.00%
0/268
|
0.00%
0/274
|
|
General disorders
Systemic inflammatory response system
|
0.00%
0/111
|
1.1%
1/90
|
0.00%
0/111
|
0.00%
0/99
|
0.00%
0/268
|
0.00%
0/274
|
|
Infections and infestations
Bursitis infected staphylococcal
|
0.90%
1/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
0.00%
0/268
|
0.00%
0/274
|
|
Infections and infestations
Pneumonia streptococcal
|
0.00%
0/111
|
0.00%
0/90
|
0.90%
1/111
|
0.00%
0/99
|
0.00%
0/268
|
0.00%
0/274
|
|
Infections and infestations
Tonsillitis
|
0.00%
0/111
|
0.00%
0/90
|
0.90%
1/111
|
0.00%
0/99
|
0.00%
0/268
|
0.00%
0/274
|
|
Injury, poisoning and procedural complications
Concussion
|
0.00%
0/111
|
0.00%
0/90
|
0.90%
1/111
|
0.00%
0/99
|
0.00%
0/268
|
0.00%
0/274
|
|
Injury, poisoning and procedural complications
Device failure
|
0.00%
0/111
|
0.00%
0/90
|
0.90%
1/111
|
0.00%
0/99
|
0.00%
0/268
|
0.00%
0/274
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/111
|
0.00%
0/90
|
0.90%
1/111
|
0.00%
0/99
|
0.00%
0/268
|
0.00%
0/274
|
|
Injury, poisoning and procedural complications
Ligament injury
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
1.0%
1/99
|
0.00%
0/268
|
0.00%
0/274
|
|
Injury, poisoning and procedural complications
Skull fractured base
|
0.00%
0/111
|
0.00%
0/90
|
0.90%
1/111
|
0.00%
0/99
|
0.00%
0/268
|
0.00%
0/274
|
|
Musculoskeletal and connective tissue disorders
Arthropathy
|
0.90%
1/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
0.00%
0/268
|
0.00%
0/274
|
|
Musculoskeletal and connective tissue disorders
Spondylolisthesis acquired
|
0.90%
1/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
0.00%
0/268
|
0.00%
0/274
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastrointestinal carcinoma
|
0.00%
0/111
|
1.1%
1/90
|
0.00%
0/111
|
0.00%
0/99
|
0.00%
0/268
|
0.00%
0/274
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung cancer metastatic
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
1.0%
1/99
|
0.00%
0/268
|
0.00%
0/274
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant melanoma of sights other than skin
|
0.00%
0/111
|
1.1%
1/90
|
0.00%
0/111
|
0.00%
0/99
|
0.00%
0/268
|
0.00%
0/274
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to lung
|
0.00%
0/111
|
1.1%
1/90
|
0.00%
0/111
|
0.00%
0/99
|
0.00%
0/268
|
0.00%
0/274
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pancreatic carcinoma
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
1.0%
1/99
|
0.00%
0/268
|
0.00%
0/274
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Transitional cell carcinoma
|
0.00%
0/111
|
1.1%
1/90
|
0.00%
0/111
|
0.00%
0/99
|
0.00%
0/268
|
0.00%
0/274
|
|
Nervous system disorders
Cerebellar infarction
|
0.00%
0/111
|
1.1%
1/90
|
0.00%
0/111
|
0.00%
0/99
|
0.00%
0/268
|
0.00%
0/274
|
|
Nervous system disorders
Cerebral infarction
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
1.0%
1/99
|
0.00%
0/268
|
0.00%
0/274
|
|
Nervous system disorders
Cerebrovascular accident
|
0.00%
0/111
|
1.1%
1/90
|
0.00%
0/111
|
0.00%
0/99
|
0.00%
0/268
|
0.00%
0/274
|
|
Nervous system disorders
Hydrocephalus
|
0.00%
0/111
|
1.1%
1/90
|
0.00%
0/111
|
0.00%
0/99
|
0.00%
0/268
|
0.00%
0/274
|
|
Nervous system disorders
Sciatica
|
0.00%
0/111
|
1.1%
1/90
|
0.90%
1/111
|
0.00%
0/99
|
0.00%
0/268
|
0.00%
0/274
|
|
Psychiatric disorders
Confusional state
|
0.00%
0/111
|
1.1%
1/90
|
0.00%
0/111
|
0.00%
0/99
|
0.00%
0/268
|
0.00%
0/274
|
|
Psychiatric disorders
Renal and urinary disorders
|
0.90%
1/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
0.00%
0/268
|
0.00%
0/274
|
|
Psychiatric disorders
Renal colic
|
0.90%
1/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
0.00%
0/268
|
0.00%
0/274
|
|
Reproductive system and breast disorders
Testicular torsion
|
0.00%
0/111
|
0.00%
0/90
|
0.90%
1/111
|
0.00%
0/99
|
0.00%
0/268
|
0.00%
0/274
|
|
Reproductive system and breast disorders
Vaginal prolapse
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
1.0%
1/99
|
0.00%
0/268
|
0.00%
0/274
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/111
|
1.1%
1/90
|
0.00%
0/111
|
1.0%
1/99
|
0.00%
0/268
|
0.00%
0/274
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
1.0%
1/99
|
0.00%
0/268
|
0.00%
0/274
|
|
Surgical and medical procedures
Cholecystectomy
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
1.0%
1/99
|
0.00%
0/268
|
0.00%
0/274
|
|
Surgical and medical procedures
Haemorrhoid operation
|
0.00%
0/111
|
0.00%
0/90
|
0.90%
1/111
|
0.00%
0/99
|
0.00%
0/268
|
0.00%
0/274
|
|
Vascular disorders
Aneurysm
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
1.0%
1/99
|
0.00%
0/268
|
0.00%
0/274
|
Other adverse events
| Measure |
Year 1 E+M / Year 2 E+M
Following a blinded transition from year one- Etanercept injection- two injections 25 mg weekly (given at the same time at different sites)+ oral Methotrexate capsules weekly (same day as injection).
Dose consistent with the ending dose at year one (usually 20 mgs). No reduction of MTX dose is permitted in year two.
|
Year 1 M / Year 2 E+M
Following a blinded transition from year one- Etanercept two injections 25 mg weekly (given at the same time at different sites) + oral Methotrexate capsules weekly (same day as injection).
Dose consistent with the ending dose at year one (usually 20 mgs). No reduction of MTX dose is permitted in year two.
|
Year 1 E+M / Year 2 E
Following a blinded transition from year one-Etanercept two injections 25 mg weekly (given at the same time at different sites).
|
Year 1 M / Year 2 M
Following a blinded transition from year one- Methotrexate dose consistent with the ending dose of year one (usually 20 mgs).
No reduction of MTX dose is permitted in year two.
|
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.
|
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.
|
|---|---|---|---|---|---|---|
|
Blood and lymphatic system disorders
Blood and lymphatic
|
5.4%
6/111
|
2.2%
2/90
|
1.8%
2/111
|
4.0%
4/99
|
1.5%
4/268
|
7.3%
20/274
|
|
Cardiac disorders
Cardiac disorders
|
0.00%
0/111
|
5.6%
5/90
|
2.7%
3/111
|
1.0%
1/99
|
5.2%
14/268
|
5.1%
14/274
|
|
Ear and labyrinth disorders
Ear and labyrinth
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
6.0%
16/268
|
4.0%
11/274
|
|
Eye disorders
Eye
|
4.5%
5/111
|
4.4%
4/90
|
4.5%
5/111
|
7.1%
7/99
|
7.5%
20/268
|
10.2%
28/274
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
10.1%
27/268
|
8.4%
23/274
|
|
Gastrointestinal disorders
Diarhhea
|
3.6%
4/111
|
2.2%
2/90
|
5.4%
6/111
|
7.1%
7/99
|
7.5%
20/268
|
8.8%
24/274
|
|
Gastrointestinal disorders
Nausea
|
7.2%
8/111
|
8.9%
8/90
|
3.6%
4/111
|
8.1%
8/99
|
17.9%
48/268
|
19.3%
53/274
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
6.7%
18/268
|
4.0%
11/274
|
|
General disorders
Administration site conditions
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
18.7%
50/268
|
24.5%
67/274
|
|
Infections and infestations
Nasopharyngitis
|
9.0%
10/111
|
11.1%
10/90
|
9.0%
10/111
|
13.1%
13/99
|
15.7%
42/268
|
16.1%
44/274
|
|
Infections and infestations
Upper respiratory tract infections
|
5.4%
6/111
|
8.9%
8/90
|
4.5%
5/111
|
9.1%
9/99
|
7.1%
19/268
|
6.6%
18/274
|
|
Infections and infestations
Urinary tract infections
|
0.00%
0/111
|
2.2%
2/90
|
5.4%
6/111
|
4.0%
4/99
|
3.7%
10/268
|
6.2%
17/274
|
|
Injury, poisoning and procedural complications
Post procedural nausea
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
8.6%
23/268
|
6.6%
18/274
|
|
Investigations
Investigations
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
18.7%
50/268
|
17.9%
49/274
|
|
Musculoskeletal and connective tissue disorders
Rheumatoid arthritis
|
5.4%
6/111
|
6.7%
6/90
|
3.6%
4/111
|
15.2%
15/99
|
13.4%
36/268
|
4.7%
13/274
|
|
Nervous system disorders
Headache
|
7.2%
8/111
|
4.4%
4/90
|
5.4%
6/111
|
4.0%
4/99
|
7.5%
20/268
|
10.6%
29/274
|
|
Psychiatric disorders
Psychiatric
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
8.6%
23/268
|
10.2%
28/274
|
|
Renal and urinary disorders
Renal and urinary
|
7.2%
8/111
|
5.6%
5/90
|
1.8%
2/111
|
5.1%
5/99
|
7.1%
19/268
|
7.7%
21/274
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
6.3%
7/111
|
2.2%
2/90
|
7.2%
8/111
|
6.1%
6/99
|
9.7%
26/268
|
8.4%
23/274
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
0.00%
0/111
|
0.00%
0/90
|
0.00%
0/111
|
0.00%
0/99
|
3.0%
8/268
|
5.5%
15/274
|
|
Skin and subcutaneous tissue disorders
Rash
|
3.6%
4/111
|
5.6%
5/90
|
2.7%
3/111
|
4.0%
4/99
|
5.2%
14/268
|
5.8%
16/274
|
|
Vascular disorders
Hypertension
|
4.5%
5/111
|
0.00%
0/90
|
2.7%
3/111
|
6.1%
6/99
|
8.2%
22/268
|
6.2%
17/274
|
|
Gastrointestinal disorders
Dyspepsia
|
0.90%
1/111
|
0.00%
0/90
|
2.7%
3/111
|
5.1%
5/99
|
0.00%
0/268
|
0.00%
0/274
|
|
General disorders
Infections and Infestations
|
42.3%
47/111
|
36.7%
33/90
|
44.1%
49/111
|
42.4%
42/99
|
0.00%
0/268
|
0.00%
0/274
|
|
General disorders
Gastroenteritis
|
6.3%
7/111
|
1.1%
1/90
|
0.90%
1/111
|
1.0%
1/99
|
0.00%
0/268
|
0.00%
0/274
|
|
General disorders
Lower respiratory tract infection
|
1.8%
2/111
|
1.1%
1/90
|
3.6%
4/111
|
5.1%
5/99
|
0.00%
0/268
|
0.00%
0/274
|
|
General disorders
Rhinitis
|
1.8%
2/111
|
2.2%
2/90
|
5.4%
6/111
|
1.0%
1/99
|
0.00%
0/268
|
0.00%
0/274
|
|
Injury, poisoning and procedural complications
Injury, poisoning and procedural complications
|
11.7%
13/111
|
12.2%
11/90
|
13.5%
15/111
|
9.1%
9/99
|
0.00%
0/268
|
0.00%
0/274
|
|
Investigations
Alanine aminotransferase increased
|
4.5%
5/111
|
7.8%
7/90
|
1.8%
2/111
|
1.0%
1/99
|
0.00%
0/268
|
0.00%
0/274
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
1.8%
2/111
|
3.3%
3/90
|
3.6%
4/111
|
6.1%
6/99
|
0.00%
0/268
|
0.00%
0/274
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign
|
0.00%
0/111
|
7.8%
7/90
|
1.8%
2/111
|
3.0%
3/99
|
0.00%
0/268
|
0.00%
0/274
|
|
Psychiatric disorders
Depression
|
0.90%
1/111
|
5.6%
5/90
|
0.00%
0/111
|
0.00%
0/99
|
0.00%
0/268
|
0.00%
0/274
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The PIs agreed to allow the sponsor 60 days to review and require changes to presentations or publications but only to protect confidential information and intellectual property, and for the sponsor to file a patent application, as applicable. The PIs also agreed for data to be presented first as a joint, multi-center publication.
- Publication restrictions are in place
Restriction type: OTHER