IN MODERATE TO SEVERE RA
ENBREL Structural Efficacy

Continued therapy with ENBREL showed significant radiographic inhibition

Patients on ENBREL + MTX achieved significant inhibition of radiographic progression vs MTX^1,2

ENBREL has been studied in a number of clinical trials including the COMET and TEMPO studies.

The COMET study included patients with early (<2 years) moderate to severe RA
The TEMPO study included patients who had moderate to severe RA and had an inadequate response to at least one prior DMARD

TEMPO
COMET

Modified Total Sharp Scores (mTSS) at 3 years in the TEMPO^* Trial¹

With ENBREL + MTX, Total Sharp Score stayed below baseline for 3 years²

Change in modified Total Sharp Scores (mTSS) in the Year 2 Population^*

The COMET Trial was a 24-month, randomized, double-blind study of 542 moderate to severe early RA patients divided into two 1-year periods^1,2
Patients treated continuously with ENBREL + MTX demonstrated significantly greater radiographic inhibition compared with subjects who received MTX monotherapy over 2 years¹^¶
The addition of ENBREL to MTX monotherapy at the end of Year 1 considerably slowed radiographic progression; however, it was not as effective as continuous treatment with ENBREL + MTX¹^¶
Maintaining ENBREL monotherapy after discontinuing MTX treatment at the end of Year 1 was also effective in continuing to inhibit the rate of radiographic progression¹^¶

^¶primary endpoint

See Footnotes section for P-values.

Understanding mTSS Data and Methods Expand/Collapse

mTSS is calculated using the modified Sharp/van der Heijde method and is based on combined scores of joint erosions in the hands on a scale of 0 to 5, feet on a scale of 0 to 10 (0 = no damage), and joint space narrowing in hands and feet on a scale of 0 to 4 (0 = no narrowing). All radiographic data are based on the radiographic ITT analysis defined as all randomly assigned patients with acceptable baseline and postbaseline radiographs. Linear extrapolation methodology was used.

Per protocol, in order to read the Year 3 data, the Years 1 and 2 data were reread. Because of the known variability in reading of the radiographic images in RA, all radiographs were reread, blinded to patient and time point, by the two physicians who read the images for the Year 2 report. Thus, the Year 3 scoring of the radiographic images is considered a new reading of the years 1 and 2 time points.²

Footnotes Expand/Collapse

mTSS is calculated using the modified Sharp/van der Heijde method and is based on combined scores of joint erosions in the hands on a scale of 0 to 5, feet on a scale of 0-10 (0 = no damage), and joint space narrowing in hands and feet on a scale of 0 to 4 (0 = no narrowing). All radiographic data are based on the radiographic ITT analysis defined as all randomly assigned patients with acceptable baseline and postbaseline radiographs. Linear extrapolation methodology was used.

^*TEMPO = Trial of Etanercept and Methotrexate with Radiographic Patient Outcomes.

TEMPO Study Description Expand/Collapse

THE TEMPO Trial^1-3:

Multicenter, double-blind, European, Australian, and Israeli trial of 682 patients with moderately to severely active RA (mean duration of disease: 7 years) who had an inadequate response to at least one prior DMARD but were not refractory to MTX
Patients were randomized to receive MTX monotherapy (n = 228), twice-weekly ENBREL 25 mg as monotherapy (n = 223), or twice-weekly ENBREL 25 mg in combination with MTX (n = 231)
- All patients receiving MTX started at a dose of 7.5 mg/week whereby inadequate responders could be rapidly escalated up to 20 mg/week by Week 8
Use of concomitant corticosteroids and/or nonsteroidal anti-inflammatory drugs (NSAIDs) was permitted. All data based on ITT, LOCF analysis except where otherwise noted
The primary clinical endpoint was the area under the curve (AUC) of the ACR numeric score at 24 weeks
The primary radiographic endpoint was the change from baseline in TSS at 12 months

References

Enbrel^® (etanercept) Prescribing Information. Thousand Oaks, CA: Immunex Corporation; February 2011.
Klareskog L, van der Heijde D, de Jager JP, et al, for the TEMPO (Trial of Etanercept and Methotrexate with Radiographic Patient Outcomes) study investigators. Therapeutic effect of the combination of etanercept and methotrexate compared with each treatment alone in patients with rheumatoid arthritis: double-blind randomised controlled trial. Lancet. 2004;363:675-681.
Data on file, Amgen.

Understanding mTSS Data and Methods Expand/Collapse

At 52 weeks, the mean change in mTSS was 0.27 for ENBREL + MTX patients, vs 2.44 for MTX monotherapy patients (P < 0.001, Year-1 radiographic ITT population, N = 476.)³

Patients treated continuously with ENBREL + MTX achieved statistically significant radiographic inhibition compared with MTX alone at 1 and 2 years¹
The addition of ENBREL to MTX monotherapy at 1 year favorably altered the rate of radiographic progression through 2 years¹
Patients who moved from combination therapy to ENBREL monotherapy at 1 year significantly inhibited radiographic progression through 2 years compared with MTX alone¹

Footnotes Expand/Collapse

^*Continuous ENBREL + MTX for Year 1 and Year 2 in the COMET trial based on the population who completed Year 1. Entering into period 2 was permitted only for patients who completed Year 1 visits through 52 weeks. In LOCF analyses of Year 2 data, patients who had visits through 52 weeks and 1 additional Year 2 visit were included in the LOCF analysis.²

^†At Year 1, P < 0.001 for the ENBREL + MTX vs MTX→ENBREL + MTX arms.

^‡At Year 1, P < 0.002 for the ENBREL + MTX vs MTX arms.

^§At Year 2, P < 0.001 for the ENBREL + MTX vs the MTX→ENBREL + MTX arm and the MTX arm.

^||One subject did not have a valid radiograph at Week 52, but did at baseline and Week 104; change from Week 52 to Week 104 cannot be assessed.

COMET Study Description Expand/Collapse

The COMET Trial^1-3:

Year 1

24-month, randomized, double-blind, two-period trial of 542 patients with moderately to severely active RA (from ≥3 months' to ≤2 years' duration). Mean duration of disease for these patients was 9 months
At baseline: patients were ≥18 years of age, were MTX-naive, had a DAS 28 ≥3.2, had either an erythrocyte sedimentation rate (ESR) ≥28 mm/hr or C-reactive protein (CRP) level ≥20 mg/L, and were within ACR Functional Class I, II, or III
Corticosteroids (≤10 mg prednisone or equivalent) and NSAIDs were allowed if the dose was stable for at least 4 weeks prior to baseline. The doses were required to be kept constant through 24 weeks unless the patient experienced an adverse event. DMARDs other than MTX and ENBREL were not allowed

Study Design^1,2:

The 2-year COMET trial was divided into two periods, each lasting 1 year
The primary objective was to compare the effects of ENBREL + MTX to MTX on clinical disease activity and radiographic change over 1 year (Period 1) in subjects with active early RA
Results for both 1- and 2-year analyses should be viewed in context with the populations evaluated for each time point
During Period 1 of the trial, patients were randomized to receive once-weekly ENBREL 50 mg in combination with weekly MTX (n = 274) or MTX alone (n = 268). In both the combination and monotherapy groups, initial MTX therapy dose was 7.5 mg, which was titrated to 15 mg at Week 4 if response was inadequate, and further titrated at Week 8 if patients still responded inadequately (maximum dose was 20 mg/week)
From Weeks 8 to 52, the mean (median) MTX therapy doses were: ENBREL + MTX = 16 mg/week (17 mg/week); MTX monotherapy = 17 mg/week (20 mg/week)

Treatment Groups^1,2:

Subjects were randomized at the baseline visit equally to 1 of 4 groups
- Group 1A: ENBREL + MTX in Periods 1 and 2
- Group 1B: ENBREL + MTX in Period 1 and ENBREL alone in Period 2
- Group 2A: MTX alone in Period 1 and ENBREL + MTX in Period 2
- Group 2B: MTX in Periods 1 and 2
131 (24.2%) subjects discontinued during Year 1 of the study: 79 (29.5%) in the MTX group and 52 (19%) in the ENBREL + MTX treatment group

1-Year Endpoints²:

Clinical endpoints included: DAS 28 clinical remission at Month 12, DAS 44 clinical remission, and ACR 20/50/70
Radiographic endpoint: change in mTSS at Month 12 (components of TSS are joint space narrowing and joint erosion scores)

Safety Analyses^1,2:

Safety was analyzed using the intent-to-treat (ITT) population (N = 542), which was defined as all enrolled subjects in the trial who received at least 1 dose of the study drug

Efficacy Analyses²:

The primary clinical efficacy endpoint was DAS 28 clinical remission (<2.6) at Month 12
For Period 1 analyses, the modified ITT (mITT) population included all subjects who received at least 1 dose of drug and had baseline and ≥1 postbaseline DAS 28 results (N = 265 for ENBREL + MTX, N = 263 for MTX alone)
The primary radiographic endpoint was the change in mTSS over 12 months
Radiographic analyses for Period 1 included only subjects with baseline and follow-up x-rays (N = 246 for ENBREL + MTX, N = 230 for MTX alone)

Year 2

^*One subject (Group 1B) discontinued at final Year 1 visit but received 1 dose of the study drug in Year 2 and was included in the Year 2 population.

Study Design^1,2:

The MTX or MTX-matching placebo dose level at the end of Period 1 was the starting dose level for MTX or MTX-matching placebo in Period 2. Subjects in Group 1B (ENBREL + MTX/ENBREL) discontinued MTX by the end of the fourth week of Period 2 (ie, by the start of Month 13 of the study). In Year 2, the mean doses of MTX (mg/week) were similar between groups: 16.19 in Group 1A, 16.26 in Group 1B (mean MTX dose reported was specific to the withdrawal period [~4 weeks]), 17.83 in Group 2A, and 18.03 in Group 2B

Treatment Groups¹:

Subjects who met inclusion criteria for Period 1 and completed Period 1 were eligible to participate in Period 2
No re-randomization of subjects in Year 2
64 patients discontinued during Year 2: 7 in Group 1A, 16 in Group 2A, 18 in Group 1B, and 23 in Group 2B

2-Year Endpoints¹:

Evaluate the safety of each treatment group during Year 2
Compare the effects of ENBREL + MTX to MTX alone on radiographic change and clinical disease activity in Period 2 in subjects who first received MTX alone for 1 year
Compare the effects of ENBREL + MTX to ENBREL alone on radiographic change and clinical disease activity in Period 2 in subjects who first received ENBREL + MTX for 1 year
Compare the effects of ENBREL + MTX for 2 years to MTX alone for 1 year, followed by ENBREL + MTX on radiographic change and clinical disease activity over 2 years
Compare the effects of ENBREL + MTX on radiographic change and clinical disease activity to MTX alone over 2 years

Safety Analyses^1,2:

The ITT population (N = 411) was defined as all subjects who received at least 1 dose of study drug during Period 2

Efficacy Analyses¹:

The mITT population was defined as all subjects who received at least 1 dose of study drug and had Year 2 baseline and ≥1 post-Year 2 baseline DAS 28 results
- For other analyses, fewer subjects may have been included if they were missing data for that particular endpoint
Data analyses performed upon completion of Year 2 included data generated by subjects during Year 1 of the COMET trial
There were 2 baselines for Year 2 analyses: the original baseline at the beginning of Year 1 and the Year 2 baseline (Week 52)
The radiographic ITT population received at least 1 dose of study drug and provided data at baseline, Year 1, and during Year 2
Nonresponder imputation (NRI) population analyses included patients who received at least 1 dose of study drug and had at least 1 post-Year 1 baseline on-therapy ACR result (N = 488)

References

Data on file, Pfizer Inc.
Emery P, Breedveld FC, Hall S, et al. Comparison of methotrexate monotherapy with a combination of methotrexate and etanercept in active, early, moderate to severe rheumatoid arthritis (COMET): a randomised, double-blind, parallel treatment trial. Lancet. 2008;372:375-382.
Hochberg MC, Chang RW, Dwosh I, Lindsey S, Pincus T, Wolfe F. The American College of Rheumatology 1991 revised criteria for the classification of global functional status in rheumatoid arthritis. Arthritis Rheum. 1992;35:498-502.

View Study Designs and Descriptions

TEMPO
COMET Year 1
COMET Year 2

No Radiographic Progression--Change in TSS ≤ 0.0 Units^2,4

All radiographic data based on ITT analysis of patients with an acceptable baseline and postbaseline radiograph. Linear extrapolation methodology was used.

Percentage of patients with no radiographic progression at 1 year (Δ in mTSS ≤ 0.0)¹

Percentage of patients with no further radiographic progression from the end of Year 1 to the end of Year 2 (Δ in mTSS ≤ 0.0) based on the Year 2 population^||||##

While early therapy led to the best radiographic outcomes, ENBREL + MTX continued to inhibit radiographic progression over 2 years⁵

During Year 2, radiographic nonprogression was demonstrated in a significantly higher proportion of patients in the ENBREL + MTX group vs. patients in the ENBREL + MTX→ENBREL group (71%), the MTX→MTX + ENBREL group, and the MTX→MTX group (58%)⁵

Patients treated continuously with ENBREL + MTX for 2 years achieved significantly better results than patients who added ENBREL to their MTX treatment at the end of Year 1.⁵

^||||For this analysis, all radiographs were reread.

^##The population evaluated for radiographic progression decreased from the 411 who received at least 1 dose of study drug during Year 2 to 361. The difference was due to 50 patients discontinuing the trial or radiographs that were either unreadable or not obtained.

TEMPO Study Description Expand/Collapse

THE TEMPO Trial^1-3:

Multicenter, double-blind, European, Australian, and Israeli trial of 682 patients with moderately to severely active RA (mean duration of disease: 7 years) who had an inadequate response to at least one prior DMARD but were not refractory to MTX
Patients were randomized to receive MTX monotherapy (n = 228), twice-weekly ENBREL 25 mg as monotherapy (n = 223), or twice-weekly ENBREL 25 mg in combination with MTX (n = 231)
- All patients receiving MTX started at a dose of 7.5 mg/week whereby inadequate responders could be rapidly escalated up to 20 mg/week by Week 8
Use of concomitant corticosteroids and/or nonsteroidal anti-inflammatory drugs (NSAIDs) was permitted. All data based on ITT, LOCF analysis except where otherwise noted
The primary clinical endpoint was the area under the curve (AUC) of the ACR numeric score at 24 weeks
The primary radiographic endpoint was the change from baseline in TSS at 12 months

References

Enbrel^® (etanercept) Prescribing Information. Thousand Oaks, CA: Immunex Corporation; February 2011.
Klareskog L, van der Heijde D, de Jager JP, et al, for the TEMPO (Trial of Etanercept and Methotrexate with Radiographic Patient Outcomes) study investigators. Therapeutic effect of the combination of etanercept and methotrexate compared with each treatment alone in patients with rheumatoid arthritis: double-blind randomised controlled trial. Lancet. 2004;363:675-681.
Data on file, Amgen.

COMET Study Description Expand/Collapse

The COMET Trial^1-3:

Year 1

24-month, randomized, double-blind, two-period trial of 542 patients with moderately to severely active RA (from ≥3 months' to ≤2 years' duration). Mean duration of disease for these patients was 9 months
At baseline: patients were ≥18 years of age, were MTX-naive, had a DAS 28 ≥3.2, had either an erythrocyte sedimentation rate (ESR) ≥28 mm/hr or C-reactive protein (CRP) level ≥20 mg/L, and were within ACR Functional Class I, II, or III
Corticosteroids (≤10 mg prednisone or equivalent) and NSAIDs were allowed if the dose was stable for at least 4 weeks prior to baseline. The doses were required to be kept constant through 24 weeks unless the patient experienced an adverse event. DMARDs other than MTX and ENBREL were not allowed

Study Design^1,2:

The 2-year COMET trial was divided into two periods, each lasting 1 year
The primary objective was to compare the effects of ENBREL + MTX to MTX on clinical disease activity and radiographic change over 1 year (Period 1) in subjects with active early RA
Results for both 1- and 2-year analyses should be viewed in context with the populations evaluated for each time point
During Period 1 of the trial, patients were randomized to receive once-weekly ENBREL 50 mg in combination with weekly MTX (n = 274) or MTX alone (n = 268). In both the combination and monotherapy groups, initial MTX therapy dose was 7.5 mg, which was titrated to 15 mg at Week 4 if response was inadequate, and further titrated at Week 8 if patients still responded inadequately (maximum dose was 20 mg/week)
From Weeks 8 to 52, the mean (median) MTX therapy doses were: ENBREL + MTX = 16 mg/week (17 mg/week); MTX monotherapy = 17 mg/week (20 mg/week)

Treatment Groups^1,2:

Subjects were randomized at the baseline visit equally to 1 of 4 groups
- Group 1A: ENBREL + MTX in Periods 1 and 2
- Group 1B: ENBREL + MTX in Period 1 and ENBREL alone in Period 2
- Group 2A: MTX alone in Period 1 and ENBREL + MTX in Period 2
- Group 2B: MTX in Periods 1 and 2
131 (24.2%) subjects discontinued during Year 1 of the study: 79 (29.5%) in the MTX group and 52 (19%) in the ENBREL + MTX treatment group

1-Year Endpoints²:

Clinical endpoints included: DAS 28 clinical remission at Month 12, DAS 44 clinical remission, and ACR 20/50/70
Radiographic endpoint: change in mTSS at Month 12 (components of TSS are joint space narrowing and joint erosion scores)

Safety Analyses^1,2:

Safety was analyzed using the intent-to-treat (ITT) population (N = 542), which was defined as all enrolled subjects in the trial who received at least 1 dose of the study drug

Efficacy Analyses²:

The primary clinical efficacy endpoint was DAS 28 clinical remission (<2.6) at Month 12
For Period 1 analyses, the modified ITT (mITT) population included all subjects who received at least 1 dose of drug and had baseline and ≥1 postbaseline DAS 28 results (N = 265 for ENBREL + MTX, N = 263 for MTX alone)
The primary radiographic endpoint was the change in mTSS over 12 months
Radiographic analyses for Period 1 included only subjects with baseline and follow-up x-rays (N = 246 for ENBREL + MTX, N = 230 for MTX alone)

Year 2

^*One subject (Group 1B) discontinued at final Year 1 visit but received 1 dose of the study drug in Year 2 and was included in the Year 2 population.

Study Design^1,2:

The MTX or MTX-matching placebo dose level at the end of Period 1 was the starting dose level for MTX or MTX-matching placebo in Period 2. Subjects in Group 1B (ENBREL + MTX/ENBREL) discontinued MTX by the end of the fourth week of Period 2 (ie, by the start of Month 13 of the study). In Year 2, the mean doses of MTX (mg/week) were similar between groups: 16.19 in Group 1A, 16.26 in Group 1B (mean MTX dose reported was specific to the withdrawal period [~4 weeks]), 17.83 in Group 2A, and 18.03 in Group 2B

Treatment Groups¹:

Subjects who met inclusion criteria for Period 1 and completed Period 1 were eligible to participate in Period 2
No re-randomization of subjects in Year 2
64 patients discontinued during Year 2: 7 in Group 1A, 16 in Group 2A, 18 in Group 1B, and 23 in Group 2B

2-Year Endpoints¹:

Evaluate the safety of each treatment group during Year 2
Compare the effects of ENBREL + MTX to MTX alone on radiographic change and clinical disease activity in Period 2 in subjects who first received MTX alone for 1 year
Compare the effects of ENBREL + MTX to ENBREL alone on radiographic change and clinical disease activity in Period 2 in subjects who first received ENBREL + MTX for 1 year
Compare the effects of ENBREL + MTX for 2 years to MTX alone for 1 year, followed by ENBREL + MTX on radiographic change and clinical disease activity over 2 years
Compare the effects of ENBREL + MTX on radiographic change and clinical disease activity to MTX alone over 2 years

Safety Analyses^1,2:

The ITT population (N = 411) was defined as all subjects who received at least 1 dose of study drug during Period 2

Efficacy Analyses¹:

The mITT population was defined as all subjects who received at least 1 dose of study drug and had Year 2 baseline and ≥1 post-Year 2 baseline DAS 28 results
- For other analyses, fewer subjects may have been included if they were missing data for that particular endpoint
Data analyses performed upon completion of Year 2 included data generated by subjects during Year 1 of the COMET trial
There were 2 baselines for Year 2 analyses: the original baseline at the beginning of Year 1 and the Year 2 baseline (Week 52)
The radiographic ITT population received at least 1 dose of study drug and provided data at baseline, Year 1, and during Year 2
Nonresponder imputation (NRI) population analyses included patients who received at least 1 dose of study drug and had at least 1 post-Year 1 baseline on-therapy ACR result (N = 488)

References

Data on file, Pfizer Inc.
Emery P, Breedveld FC, Hall S, et al. Comparison of methotrexate monotherapy with a combination of methotrexate and etanercept in active, early, moderate to severe rheumatoid arthritis (COMET): a randomised, double-blind, parallel treatment trial. Lancet. 2008;372:375-382.
Hochberg MC, Chang RW, Dwosh I, Lindsey S, Pincus T, Wolfe F. The American College of Rheumatology 1991 revised criteria for the classification of global functional status in rheumatoid arthritis. Arthritis Rheum. 1992;35:498-502.

COMET Study Description Expand/Collapse

The COMET Trial^1-3:

Year 1

24-month, randomized, double-blind, two-period trial of 542 patients with moderately to severely active RA (from ≥3 months' to ≤2 years' duration). Mean duration of disease for these patients was 9 months
At baseline: patients were ≥18 years of age, were MTX-naive, had a DAS 28 ≥3.2, had either an erythrocyte sedimentation rate (ESR) ≥28 mm/hr or C-reactive protein (CRP) level ≥20 mg/L, and were within ACR Functional Class I, II, or III
Corticosteroids (≤10 mg prednisone or equivalent) and NSAIDs were allowed if the dose was stable for at least 4 weeks prior to baseline. The doses were required to be kept constant through 24 weeks unless the patient experienced an adverse event. DMARDs other than MTX and ENBREL were not allowed

Study Design^1,2:

The 2-year COMET trial was divided into two periods, each lasting 1 year
The primary objective was to compare the effects of ENBREL + MTX to MTX on clinical disease activity and radiographic change over 1 year (Period 1) in subjects with active early RA
Results for both 1- and 2-year analyses should be viewed in context with the populations evaluated for each time point
During Period 1 of the trial, patients were randomized to receive once-weekly ENBREL 50 mg in combination with weekly MTX (n = 274) or MTX alone (n = 268). In both the combination and monotherapy groups, initial MTX therapy dose was 7.5 mg, which was titrated to 15 mg at Week 4 if response was inadequate, and further titrated at Week 8 if patients still responded inadequately (maximum dose was 20 mg/week)
From Weeks 8 to 52, the mean (median) MTX therapy doses were: ENBREL + MTX = 16 mg/week (17 mg/week); MTX monotherapy = 17 mg/week (20 mg/week)

Treatment Groups^1,2:

Subjects were randomized at the baseline visit equally to 1 of 4 groups
- Group 1A: ENBREL + MTX in Periods 1 and 2
- Group 1B: ENBREL + MTX in Period 1 and ENBREL alone in Period 2
- Group 2A: MTX alone in Period 1 and ENBREL + MTX in Period 2
- Group 2B: MTX in Periods 1 and 2
131 (24.2%) subjects discontinued during Year 1 of the study: 79 (29.5%) in the MTX group and 52 (19%) in the ENBREL + MTX treatment group

1-Year Endpoints²:

Clinical endpoints included: DAS 28 clinical remission at Month 12, DAS 44 clinical remission, and ACR 20/50/70
Radiographic endpoint: change in mTSS at Month 12 (components of TSS are joint space narrowing and joint erosion scores)

Safety Analyses^1,2:

Safety was analyzed using the intent-to-treat (ITT) population (N = 542), which was defined as all enrolled subjects in the trial who received at least 1 dose of the study drug

Efficacy Analyses²:

The primary clinical efficacy endpoint was DAS 28 clinical remission (<2.6) at Month 12
For Period 1 analyses, the modified ITT (mITT) population included all subjects who received at least 1 dose of drug and had baseline and ≥1 postbaseline DAS 28 results (N = 265 for ENBREL + MTX, N = 263 for MTX alone)
The primary radiographic endpoint was the change in mTSS over 12 months
Radiographic analyses for Period 1 included only subjects with baseline and follow-up x-rays (N = 246 for ENBREL + MTX, N = 230 for MTX alone)

Year 2

^*One subject (Group 1B) discontinued at final Year 1 visit but received 1 dose of the study drug in Year 2 and was included in the Year 2 population.

Study Design^1,2:

The MTX or MTX-matching placebo dose level at the end of Period 1 was the starting dose level for MTX or MTX-matching placebo in Period 2. Subjects in Group 1B (ENBREL + MTX/ENBREL) discontinued MTX by the end of the fourth week of Period 2 (ie, by the start of Month 13 of the study). In Year 2, the mean doses of MTX (mg/week) were similar between groups: 16.19 in Group 1A, 16.26 in Group 1B (mean MTX dose reported was specific to the withdrawal period [~4 weeks]), 17.83 in Group 2A, and 18.03 in Group 2B

Treatment Groups¹:

Subjects who met inclusion criteria for Period 1 and completed Period 1 were eligible to participate in Period 2
No re-randomization of subjects in Year 2
64 patients discontinued during Year 2: 7 in Group 1A, 16 in Group 2A, 18 in Group 1B, and 23 in Group 2B

2-Year Endpoints¹:

Evaluate the safety of each treatment group during Year 2
Compare the effects of ENBREL + MTX to MTX alone on radiographic change and clinical disease activity in Period 2 in subjects who first received MTX alone for 1 year
Compare the effects of ENBREL + MTX to ENBREL alone on radiographic change and clinical disease activity in Period 2 in subjects who first received ENBREL + MTX for 1 year
Compare the effects of ENBREL + MTX for 2 years to MTX alone for 1 year, followed by ENBREL + MTX on radiographic change and clinical disease activity over 2 years
Compare the effects of ENBREL + MTX on radiographic change and clinical disease activity to MTX alone over 2 years

Safety Analyses^1,2:

The ITT population (N = 411) was defined as all subjects who received at least 1 dose of study drug during Period 2

Efficacy Analyses¹:

The mITT population was defined as all subjects who received at least 1 dose of study drug and had Year 2 baseline and ≥1 post-Year 2 baseline DAS 28 results
- For other analyses, fewer subjects may have been included if they were missing data for that particular endpoint
Data analyses performed upon completion of Year 2 included data generated by subjects during Year 1 of the COMET trial
There were 2 baselines for Year 2 analyses: the original baseline at the beginning of Year 1 and the Year 2 baseline (Week 52)
The radiographic ITT population received at least 1 dose of study drug and provided data at baseline, Year 1, and during Year 2
Nonresponder imputation (NRI) population analyses included patients who received at least 1 dose of study drug and had at least 1 post-Year 1 baseline on-therapy ACR result (N = 488)

References

Data on file, Pfizer Inc.
Emery P, Breedveld FC, Hall S, et al. Comparison of methotrexate monotherapy with a combination of methotrexate and etanercept in active, early, moderate to severe rheumatoid arthritis (COMET): a randomised, double-blind, parallel treatment trial. Lancet. 2008;372:375-382.
Hochberg MC, Chang RW, Dwosh I, Lindsey S, Pincus T, Wolfe F. The American College of Rheumatology 1991 revised criteria for the classification of global functional status in rheumatoid arthritis. Arthritis Rheum. 1992;35:498-502.

View Study Designs and Descriptions

Improve Physical Function Reduce Signs and Symptoms

Important Safety Information Prescribing Information Medication Guide

Indications

Moderate to Severe Rheumatoid Arthritis Supportive Data

View in-depth ENBREL efficacy data from the COMET trial

Explore 3 measures of efficacy in moderate to severe RA with COMET Interactive.

Take a deeper look

Consider ENBREL “NOW” to help inhibit progression of structural damage

Watch a brief video about the interrelated processes of inflammatory disease activity and the development of structural damage.

Play Video

It didn't take long before Tami started to notice a difference after she started ENBREL.

Tami G., ENBREL RA patient since 1999

Prescribing Information Medication Guide

IN MODERATE TO SEVERE RAENBREL Structural Efficacy

Continued therapy with ENBREL showed significant radiographic inhibition

Modified Total Sharp Scores (mTSS) at 3 years in the TEMPO* Trial1

Change in modified Total Sharp Scores (mTSS) in the Year 2 Population*

THE TEMPO Trial1-3:

References

The COMET Trial1-3:

Year 1

Study Design1,2:

Treatment Groups1,2:

1-Year Endpoints2:

Safety Analyses1,2:

Efficacy Analyses2:

Year 2

Study Design1,2:

Treatment Groups1:

2-Year Endpoints1:

Safety Analyses1,2:

Efficacy Analyses1:

References

No Radiographic Progression--Change in TSS ≤ 0.0 Units2,4

Percentage of patients with no radiographic progression at 1 year (Δ in mTSS ≤ 0.0)1

Percentage of patients with no further radiographic progression from the end of Year 1 to the end of Year 2 (Δ in mTSS ≤ 0.0) based on the Year 2 population||||##

THE TEMPO Trial1-3:

References

The COMET Trial1-3:

Year 1

Study Design1,2:

Treatment Groups1,2:

1-Year Endpoints2:

Safety Analyses1,2:

Efficacy Analyses2:

Year 2

Study Design1,2:

Treatment Groups1:

2-Year Endpoints1:

Safety Analyses1,2:

Efficacy Analyses1:

References

The COMET Trial1-3:

Year 1

Study Design1,2:

Treatment Groups1,2:

1-Year Endpoints2:

Safety Analyses1,2:

Efficacy Analyses2:

Year 2

Study Design1,2:

Treatment Groups1:

2-Year Endpoints1:

Safety Analyses1,2:

Efficacy Analyses1:

References

View in-depth ENBREL efficacy data from the COMET trial

Consider ENBREL “NOW” to help inhibit progression of structural damage

IN MODERATE TO SEVERE RA
ENBREL Structural Efficacy

Modified Total Sharp Scores (mTSS) at 3 years in the TEMPO^* Trial¹

Change in modified Total Sharp Scores (mTSS) in the Year 2 Population^*

THE TEMPO Trial^1-3:

The COMET Trial^1-3:

Study Design^1,2:

Treatment Groups^1,2:

1-Year Endpoints²:

Safety Analyses^1,2:

Efficacy Analyses²:

Study Design^1,2:

Treatment Groups¹:

2-Year Endpoints¹:

Safety Analyses^1,2:

Efficacy Analyses¹:

No Radiographic Progression--Change in TSS ≤ 0.0 Units^2,4

Percentage of patients with no radiographic progression at 1 year (Δ in mTSS ≤ 0.0)¹

Percentage of patients with no further radiographic progression from the end of Year 1 to the end of Year 2 (Δ in mTSS ≤ 0.0) based on the Year 2 population^||||##

THE TEMPO Trial^1-3:

The COMET Trial^1-3:

Study Design^1,2:

Treatment Groups^1,2:

1-Year Endpoints²:

Safety Analyses^1,2:

Efficacy Analyses²:

Study Design^1,2:

Treatment Groups¹:

2-Year Endpoints¹:

Safety Analyses^1,2:

Efficacy Analyses¹:

The COMET Trial^1-3:

Study Design^1,2:

Treatment Groups^1,2:

1-Year Endpoints²:

Safety Analyses^1,2:

Efficacy Analyses²:

Study Design^1,2:

Treatment Groups¹:

2-Year Endpoints¹:

Safety Analyses^1,2:

Efficacy Analyses¹: