In moderate to severe RA
Inhibit the progression of joint damage

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

ENBREL + MTX achieved significant inhibition of joint damage in modified total Sharp score (mTSS) through Year 31*

Mean change in mTSS from baseline in the TEMPO study
  • 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 MTX2,3
  • ENBREL + MTX therapy resulted in significantly less radiographic progression compared with MTX alone1
  • Patients with no radiographic progression (∆mTSS ≤ 0) at 3 years: 73% in the ENBREL + MTX arm, 60% on ENBREL alone and 50% on MTX alone1
Footnote:
  • * Per protocol, in order to read the Year 3 data (N=638), the Year 1 (N=648) and Year 2 data (N=622) were reread. Because of the known variability in reading of the radiographic images in RA, all radiographs were reread and blinded to patient and time point by the 2 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 Year 1 and Year 2 time points.1

Study Design

THE TEMPO STUDY1-3:

  • Multicenter, double-blind, European, Australian, and Israeli study 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 MTX1,2
  • 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)2
  • Use of concomitant corticosteroids and/or nonsteroidal anti-inflammatory drugs (NSAIDs) was permitted2
  • The primary clinical endpoint was the area under the curve (AUC) of the ACR numeric score at 24 weeks2
  • The primary radiographic endpoint was the change from baseline in TSS at 12 months2
  • Pain, morning stiffness, CRP, HAQ, and complete joint count were evaluated at Weeks 0, 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, 52, 60, 68, 76, 88, 100, 112, 120, 128, 140, and 1523

ENBREL+ MTX achieved significant inhibition of joint damage by mean change in modified total Sharp score (mTSS) from baseline1

Mean change in mTSS from baseline in the PRESERVE study (Period 2)
  • PRESERVE was a 2-period study of patients with moderately active RA (DAS 28 >3.2 and ≤5.1) despite treatment on MTX alone1,2
  • Period 2 of the PRESERVE study consisted of patients who achieved DAS 28 LDA in Period 1 (DAS 28 ≤3.2)2
  • At week 88, 88% of patients in the ENBREL + MTX arm and 82% of patients in the MTX arm had no radiographic progression (∆mTSS ≤ 0.0)1

Study Design

THE PRESERVE STUDY1,2:

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 achieve sustained LDA mean DAS28 ≤ from weeks 12 to 36 and DAS ≤ at week 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.

Baseline characteristics1 (N=834)

  • Period 1 was an open-label assessment of the efficacy and safety of ENBREL + MTX over 36 weeks1
  • 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 361
  • Patients must have received a stable dose of MTX (at least 15 mg/week and no more than 25 mg/week) for a minimum of 8 weeks at the time of screening1
  • Use of prednisone ≤10 mg/day was allowed during the study1
  • The primary endpoint was the proportion of patients achieving DAS 28 LDA at Week 88 (Period 2)1
  • Other key defined secondary endpoints in both periods include:
    • Proportion of patients achieving DAS 28 clinical remission1
    • Proportion of patients achieving ACR 20, ACR 50, ACR 70, and ACR 901,2
    • Change in mTSS from baseline1
  • Pain, morning stiffness, CRP, and HAQ were evaluated at Weeks 1, 4, 8, 12, 20, 28, 36, 40, 48, 56, 64, 72, 80, and 883

ENBREL + MTX achieved significant inhibition of joint damage in modified total Sharp score (mTSS) through Year 21,2

Mean change in mTSS* in Year 2 population of the COMET study
  • COMET was a 2-year study that evaluated 542 patients with moderately to severely active early RA (mean disease duration: 9 months)3
  • At the end of Year 2, 87% of patients continuously on ENBREL + MTX had no radiographic progression (Δ in mTSS ≤0.0) (LOCF) vs 58% of patients on MTX alone (P<0.001)1,2
Understanding the Data:

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.1,4,5

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).6

  • Patients treated continuously with ENBREL + MTX achieved statistically significant radiographic inhibition compared with MTX alone at 1 and 2 years2
  • The addition of ENBREL to MTX monotherapy at 1 year favorably altered the rate of radiographic progression through 2 years2
  • Patients who moved from combination therapy to ENBREL monotherapy at 1 year significantly halted radiographic progression through 2 years2
  • The addition of ENBREL to MTX monotherapy at the end of Year 1 considerably slowed radiographic progression; however, it was not as effective over 2 years as starting and continuing with ENBREL + MTX combination therapy2
  • Maintaining ENBREL monotherapy after discontinuing MTX treatment at the end of Year 1 was also effective in continuing to inhibit radiographic progression1,2
Footnotes:
  • * 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.1,4,5
  • Continuous ENBREL + MTX for Year 1 and Year 2 in the COMET study was based on the population who completed Year 1. Entering into Year 2 was permitted only for patients who completed Year 1 visits through 52 weeks. In the 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.7
  • 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.1

Study Design

THE COMET STUDY

YEAR 1

  • 24-month, randomized, double-blind, 2-period study 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 months1,2
  • 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 III1
  • 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 allowed1
STUDY DESIGN1:
  • The 2-year COMET study 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 study, 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:
  • Subjects were randomized at the baseline visit equally to 1 of 4 groups3:
    • 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 group1,3
1-YEAR ENDPOINTS:
  • Clinical endpoints included: DAS 28 clinical remission at Month 12, DAS 44 clinical remission, and ACR 20/50/701,4
  • Radiographic endpoint: change in mTSS at Month 12 (components of TSS are joint space narrowing and joint erosion scores)1
SAFETY ANALYSES:
  • Safety was analyzed using the intent-to-treat (ITT) population (N=542), which was defined as all enrolled subjects in the study who received at least 1 dose of the study drug
EFFICACY ANALYSES:
  • The primary clinical efficacy endpoint was DAS 28 clinical remission (<2.6) at Month 121
  • 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)1
  • The primary radiographic endpoint was the change in mTSS over 12 months1
  • 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)5

YEAR 2

STUDY DESIGN6:

  • 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 GROUPS (PERIOD 2):
  • Subjects who met inclusion criteria for Period 1 and completed Period 1 were eligible to participate in Period 26
  • No re-randomization of subjects in Year 27
  • 64 patients discontinued during Year 2: 7 in group 1A, 16 in group 2A, 18 in group 1B, and 23 in group 2B7
2-YEAR ENDPOINTS6:
  • 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 ANALYSES4,6:

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

EFFICACY ANALYSES:

  • 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)3,6
    • For other analyses, fewer subjects may have been included if they were missing data for that particular endpoint4
  • Data analyses performed upon completion of Year 2 included data generated by subjects during Year 1 of the COMET study6
  • There were 2 baselines for Year 2 analyses: the original baseline at the beginning of Year 1 and the Year 2 baseline (Week 52)6
  • The radiographic ITT population received at least one dose of study drug and provided data at baseline, Year 1, and during Year 28
  • 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)9
  • Pain, morning stiffness, CRP, HAQ, and complete joint count were evaluated at Weeks 0, 2, 4, 8, 12, 16, 20, 24, 36, 52, 64, 80, and 9610
 
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 clinical signs and symptoms

View data

More than 200,000 people have used the ENBREL Support™ card to help pay for ENBREL

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