In moderate to severe RA
ENBREL demonstrated significant and sustained improvements in physical function

In Moderate to Severe RA
In Moderately Active RA
In Moderate to Severe Early RA

ENBREL + MTX achieved rapid and sustained improvements in physical function by Week 2 and out to Year 3¹

Reductions in HAQ score in the TEMPO trial

View Study Design

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
Mean HAQ score at baseline, Week 2 and Year 3 were 1.7, 1.5, and 1.1 in the MTX arm and 1.8, 1.3 and .8 in the ENBREL + MTX arm respectively¹

Additional Data¹:

Reductions in HAQ score in the ENBREL monotherapy arm (n=223) were -19% at Week 2, -38% at Week 24, -40% at Year 1, -39% at Year 2, and -38% at Year 3
In the ENBREL + MTX arm, 16% of patients achieved HAQ ≤0.5 at Week 2 and 48% at Year 3. In the MTX arm, 11% of patients achieved HAQ ≤0.5 at Week 2 and 33% at Year 3

Study Design

Expand to View

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 reduced mean HAQ score as early as week 4 and out to week 36¹

Reductions in HAQ score in Period 1 of the PRESERVE trial

View Study Design

PRESERVE was a 2-period study of patients with moderately active RA (DAS 28 >3.2 and ≤5.1) despite treatment with MTX alone¹
Period 1 of the PRESERVE study was an open-label assessment of the efficacy and safety of ENBREL + MTX over 36 weeks¹
54% of patients achieved HAQ ≤0.5 at Week 36¹
Mean HAQ scores at baseline and Week 36 were 1.14 and 0.61, respectively¹

Significantly more patients who continued ENBREL + MTX sustained improvement in physical function at Week 88 vs MTX alone¹

% of patients with HAQ ≤0.5 in the PRESERVE trial (Period 2)

View Study Design

Period 2 of the PRESERVE trial consisted of patients who achieved DAS 28 LDA in Period 1 (DAS 28 ≤3.2)¹
63% of patients had HAQ ≤0.5 at Period 2 baseline in the ENBREL 50 mg + MTX QW arm (n=201) and 67% in the MTX arm (n=197)¹

Study Design

Expand to View

THE PRESERVE TRIAL¹:

PRESERVE was a 2-period study of patients (N=834) with moderately active RA (DAS 28 >3.2 and ≤5.1) despite optimal doses of MTX.

*Patients were randomized if they achieved DAS 28 ≤3.2 at Week 36 and an average DAS 28 ≤3.2 from Weeks 12 through 36.
†In Period 2, 202 patients were randomized to receive an investigational dose of ENBREL 25 mg once weekly. ENBREL 25 mg weekly is not an FDA-approved dosage.

Period 1 was an open-label assessment of the efficacy and safety of ENBREL + MTX over 36 weeks
Period 2 was a double-blind, randomized, 52-week period
- Patients entering Period 2 were required to achieve low disease activity (LDA) or remission (DAS 28 ≤3.2) at Week 36 and an average DAS 28 ≤3.2 from Week 12 through Week 36
Use of prednisone ≤10 mg/day was allowed during the trial
The primary endpoint was the proportion of patients achieving DAS 28 LDA at Week 88 (Period 2)
Other key defined secondary endpoints in both periods include:
- Proportion of patients achieving DAS 28 clinical remission
- Proportion of patients achieving ACR 20, ACR 50, ACR 70, and ACR 90
- Change in mTSS from baseline

Patients on ENBREL + MTX achieved significant improvements in physical function by Week 12 and out to Year 2¹

Reductions in HAQ score in the COMET trial Year 2 population

View Study Design

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
Mean HAQ score at baseline was 1.65 in the MTX arm (n=94) and 1.76 in the ENBREL + MTX arm (n=108). At Year 2, mean HAQ score was 0.79 in the MTX arm and 0.58 in the ENBREL + MTX arm¹

Launch COMET Interactive for a closer look

Additional Data¹:

In Year 1 of the COMET trial, the mean reductions in HAQ score in the ENBREL + MTX arm (n=256) were -50% at Week 12, -56% at Week 24, -60% at Week 36, and -61% at Year 1 (P<0.001).
In the MTX arm (n=241) mean reductions in HAQ were -32% at Week 12, -41% at Week 24, -45% at Week 36, and -44% at Year 1 (P<0.001).
In the MTX → ENBREL + MTX arm, reductions in HAQ score were -35%, -46%, -54%, and -62% at Week 12, Week 24, Year 1, and Year 2, respectively.
In the ENBREL + MTX → ENBREL arm, reductions were -52%, -60%, -63%, and -60% at the same time points.

Study Design

Expand to View

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)

Clinical Remission Signs and Symptoms

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

Learn about DAS 28 clinical remission

View data

ENBREL is the #1 most prescribed biologic by rheumatologists*

See why

*6-month average of IMS monthly NPA prescription data by rheumatologists.

IMS NPA prescription data does not include products administered by infusion.

Prescribing Information Medication Guide

In moderate to severe RAENBREL demonstrated significant and sustained improvements in physical function

ENBREL + MTX achieved rapid and sustained improvements in physical function by Week 2 and out to Year 31

Additional Data1:

Study Design

THE TEMPO TRIAL1,2:

ENBREL + MTX reduced mean HAQ score as early as week 4 and out to week 361

Significantly more patients who continued ENBREL + MTX sustained improvement in physical function at Week 88 vs MTX alone1

Study Design

THE PRESERVE TRIAL1:

Patients on ENBREL + MTX achieved significant improvements in physical function by Week 12 and out to Year 21

Additional Data1:

Study Design

THE COMET TRIAL1-3:

Learn about DAS 28 clinical remission

ENBREL is the #1 most prescribed biologic by rheumatologists*

In moderate to severe RA
ENBREL demonstrated significant and sustained improvements in physical function

ENBREL + MTX achieved rapid and sustained improvements in physical function by Week 2 and out to Year 3¹

Additional Data¹:

THE TEMPO TRIAL^1,2:

ENBREL + MTX reduced mean HAQ score as early as week 4 and out to week 36¹

Significantly more patients who continued ENBREL + MTX sustained improvement in physical function at Week 88 vs MTX alone¹

THE PRESERVE TRIAL¹:

Patients on ENBREL + MTX achieved significant improvements in physical function by Week 12 and out to Year 2¹

Additional Data¹:

THE COMET TRIAL^1-3: