In moderate to severe RA
ENBREL demonstrated rapid and sustained improvements in clinical symptoms

In Moderate to Severe RA
In Moderate to Severe Early RA

ENBREL + MTX significantly reduced swollen joint counts by Week 2 and out to Year 3¹

TEMPO was a 3-year study that evaluated 682 patients with moderately to severely active RA (mean disease duration: 7 years), who had an inadequate response to at least 1 DMARD excluding MTX^1,2
ACR 20 responses (NRI) for the ENBREL + MTX group vs MTX alone were 44% vs 19% at Week 2 and 52% vs 33% at Year 3¹

Reductions in swollen joint counts in the TEMPO trial

View Study Design

ENBREL + MTX significantly improved tender joint counts by Week 2 and out to Year 3¹

TEMPO was a 3-year study that evaluated 682 patients with moderately to severely active RA (mean disease duration: 7 years), who had an inadequate response to at least 1 DMARD excluding MTX^1,2
ACR 20 responses (NRI) for the ENBREL + MTX group vs MTX alone were 44% vs 19% at Week 2 and 52% vs 33% at Year 3¹

Reductions in tender joint counts in the TEMPO trial

View Study Design

Additional Data¹:

Mean change in SJC and TJC from baseline to Year 3

	SJC	TJC
ENBREL + MTX (n=231)	22 joints → 4 joints	34 joints → 8 joints
MTX (n=228)	23 joints → 7 joints	33 joints → 12 joints
ENBREL (n=223)	23 joints → 6 joints	35 joints → 11 joints

In the ENBREL monotherapy arm, reductions in swollen joint counts were -34%, -44%, -73%, -73%, and -72% at Week 2, Week 4, Year 1, Year 2, and Year 3, respectively
In the ENBREL monotherapy arm, reductions in tender joint counts were -32%, -38%, -66%, -69%, and -67% at Week 2, Week 4, Year 1, Year 2, and Year 3, respectively

Study Design

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THE TEMPO TRIAL^1,2:

3-year, multicenter, double-blind, European, Australian, and Israeli trial of 682 patients with moderately to severely active RA (mean disease duration: 7 years) who had an inadequate response to at least 1 prior DMARD but were not refractory to MTX
Patients were randomized to receive MTX monotherapy rapidly escalated to 20 mg/week after 8 weeks (n=228), twice-weekly ENBREL 25 mg as monotherapy (n=223), or twice-weekly ENBREL 25 mg in combination with MTX (n=231)
Use of concomitant corticosteroids and/or nonsteroidal anti-inflammatory drugs (NSAIDs) was permitted
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

ENBREL + MTX significantly improved swollen joint counts by Week 2 and out to Year 2¹

Reductions in swollen joint counts by Week 2 through Year 2 in the Year 2 population of the COMET trial

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ENBREL + MTX significantly improved tender joint counts by Week 2 and out to Year 2¹

Reductions in tender joint count in the Year 2 population of the COMET trial

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COMET was a 2-year, 2-part study that evaluated 542 patients with moderately to severely active early RA (mean disease duration: 9 months)^2,3
ACR 20 responses for the ENBREL + MTX group vs MTX alone were 49% vs 14% at Week 2 and 86% vs 61% at Year 2 (NRI)¹

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Additional Data¹:

Mean SJC and TJC from baseline to Week 2 to Year 2

	SJC	TJC
ENBREL + MTX (n=108)	13 joints → 7 joints → 1 joint	14 joints → 8 joints → 2 joints
MTX (n=94)	12 joints → 10 joints → 3 joints	14 joints → 12 joints → 4 joints

At Year 2, reductions in swollen joint counts were -90% in the MTX → ENBREL + MTX arm (n=88) and -85% in the ENBREL + MTX → ENBREL arm (n=108)
At Year 2, reductions in tender joint counts were -86% in the MTX → ENBREL + MTX arm (n=88) and -78% in the ENBREL + MTX → ENBREL arm (n=108)

Year 1 Data:

Reductions in swollen joints in the ENBREL + MTX arm were -42% at Week 2, -55% at Week 4, and -85% at Year 1. Reductions for the MTX monotherapy arm were -16%, -22%, and -65% at Week 2, Week 4, and Year 1, respectively
Reductions in tender joints in the ENBREL + MTX arm were -41% at Week 2, -52% at Week 4, and -79% at Year 1. Reductions for the MTX monotherapy arm were -13%, -21%, and -60% at Week 2, Week 4, and Year 1, respectively

Study Design

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THE COMET TRIAL^1-3:

24-month, randomized, double-blind, 2-period trial of 542 patients with moderately to severely active early 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 ESR ≥28 mm/hr or C-reactive protein (CRP) level ≥20 mg/L, and were within ACR Functional Class I, II, or III

Study Design^1,2:

Corticosteroids (≤10 mg/day 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
The 2-year COMET trial was divided into 2 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 moderate to severe 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 (19.0%) 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)

Study Design¹:

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 result(s)
- 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 one 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)

Physical Function Moderate to Severe Rheumatoid Arthritis and ENBREL

Supportive data

Moderate to Severe Rheumatoid Arthritis

In medical studies, ENBREL was shown to be clinically effective in about 2 out of 3 adults with moderate to severe RA at 3 months. ENBREL has been shown to begin working in as few as 2 weeks, and most patients who benefit will do so within 3 months. In another medical study, 55% of patients who were evaluated 5 years after beginning ENBREL therapy had no further progression of joint damage.

Psoriatic Arthritis

In a medical study, ENBREL was shown to be effective in about 50% of psoriatic arthritis patients at 6 months. Clinical responses were apparent at the time of the first visit (4 weeks) and were maintained through 6 months of therapy.

Important Safety Considerations

In moderate to severe RA

ENBREL improved physical function

View data

The experience of ENBREL

Evaluated in clinical studies over the past 19 years*

See our history of "1sts"

*Initial clinical research in RA patients began in 1993. Approved to treat moderate to severe RA in 1998.

Prescribing Information Medication Guide

In moderate to severe RAENBREL demonstrated rapid and sustained improvements in clinical symptoms

ENBREL + MTX significantly reduced swollen joint counts by Week 2 and out to Year 31

ENBREL + MTX significantly improved tender joint counts by Week 2 and out to Year 31

Additional Data1:

Study Design

THE TEMPO TRIAL1,2:

ENBREL + MTX significantly improved swollen joint counts by Week 2 and out to Year 21

ENBREL + MTX significantly improved tender joint counts by Week 2 and out to Year 21

Additional Data1:

Year 1 Data:

Study Design

THE COMET TRIAL1-3:

ENBREL improved physical function

The experience of ENBREL

In moderate to severe RA
ENBREL demonstrated rapid and sustained improvements in clinical symptoms

ENBREL + MTX significantly reduced swollen joint counts by Week 2 and out to Year 3¹

ENBREL + MTX significantly improved tender joint counts by Week 2 and out to Year 3¹

Additional Data¹:

THE TEMPO TRIAL^1,2:

ENBREL + MTX significantly improved swollen joint counts by Week 2 and out to Year 2¹

ENBREL + MTX significantly improved tender joint counts by Week 2 and out to Year 2¹

Additional Data¹:

THE COMET TRIAL^1-3: