In moderate to severe RA
Help patients to achieve DAS 28 clinical remission

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

Rapid and sustained efficacy by week 4 and out to year 31

Patients achieving DAS 28 clinical remission in the TEMPO study

LOCF=last observation carried forward.

DAS 28 clinical remission does not mean drug-free remission or complete absence of disease.

  • 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
ACR responses
  • ACR 20/50/70 rates at Week 4 were 58%/20%/7% for ENBREL + MTX and 34%/4%/0% for MTX alone4
  • ACR 20/50/70 rates at Year 3 were 52%/43%/31% for ENBREL + MTX and 33%/24%/13% for MTX alone (NRI)4
  • See study design for additional information
Additional Data:

In the ENBREL (n=223) arm of the TEMPO study, the percent of patients achieving DAS 28 clinical remission was 3%, 8%, 14%, 18%, 22%, and 22% at Week 4, Week 12, Week 24, Year 1, Year 2, and Year 3 respectively.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

At week 36, nearly 2/3 of patients achieved DAS 28 clinical remission* when ENBREL was added to MTX1

Patients with DAS 28 clinical remission with ENBREL + MTX in the PRESERVE study (Period 1)
LOCF=last observation carried forward.

DAS 28 clinical remission does not mean drug-free remission or complete absence of disease.

  • PRESERVE was a 2-period study of patients with moderately active RA (DAS 28 >3.2 and ≤5.1) despite treatment with MTX alone1,2
  • Period 1 was an open-label assessment of the efficacy and safety of ENBREL + MTX over 36 weeks1
  • At Week 36, ACR 20/50/70 responses were achieved in 73%, 60%, and 28% of patients, respectively1
  • See study design for additional information
Footnotes:
  • * DAS 28 <2.6
  • Not all patients were evaluated for DAS 28 at all time points.1
  • Mean DAS 28 score improved from 4.4 to 2.5 from baseline to Week 36.1
  • 82% of patients achieved DAS 28 LDA (DAS 28 ≤3.2) at Week 36 in Period 1.1

Significantly more patients who continued ENBREL + MTX achieved DAS 28 clinical remission* through week 88 vs those who received MTX alone2

Patients with DAS 28 clinical remission at week 88 in the PRESERVE study (Period 2)
LOCF=last observation carried forward.

DAS 28 clinical remission does not mean drug-free remission or complete absence of disease.

  • Period 2 of the PRESERVE study consisted of patients who achieved DAS 28 LDA in Period 1 (DAS 28 ≤3.2)1
  • At period 2 baseline, 81% of patients in the ENBREL + MTX arm and 80% of patients in the MTX arm were in DAS 28 clinical remission2
  • At Week 88, ACR 70 responses were achieved in 36% of patients in the ENBREL + MTX group and 11% in the MTX group (LOCF)2
  • See study design for additional information
Footnotes:
  • * DAS 28 <2.6
  • Patients maintaining DAS 28 LDA in Period 2: 83% with ENBREL + MTX vs 43% with MTX alone (P<0.0001, primary endpoint).2

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

Rapid and sustained efficacy by week 4 and out to year 21

Patients achieving DAS 28 clinical remission in the COMET study (Year 2 population)
LOCF=last observation carried forward.

DAS 28 clinical remission does not mean drug-free remission or complete absence of disease.

  • 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
  • See the study design section for information about Year 1 and Year 2 study populations
ACR 70 nonresponder imputation (NRI) results3
2-year ACR 70 NRI methodology based on Year 1 baseline

#P≤0.037 vs MTX at all time points.

  • In clinical studies, responses (ACR 20) generally appeared within 2 weeks and nearly always occurred by 3 months4
  • DAS 44** clinical remission was achieved by 62% of patients in the ENBREL + MTX group (n=108) and 61% in the MTX → ENBREL + MTX group (n=88)1
Year 1 Data (all randomized patients)

DAS 28 clinical remission was achieved by 50% of patients in the ENBREL + MTX group (n=265) and 28% in the MTX group (n=263) (P<0.001) (primary endpoint).5

DAS 44 clinical remission was achieved by 51% of patients in the ENBREL + MTX group (n=265) and 28% in the MTX group (n=263) (P<0.001, modified intent-to-treat [mITT]).5

ACR 70 was achieved by 44% of patients in the ENBREL + MTX group (n=256) and 26% in the MTX group (n=243) (P<0.001), using non-responder imputation (NRI).6

Additional Data:
  • DAS 28 clinical remission was achieved by 50% of patients in the ENBREL + MTX → ENBREL group (n=108) and 58% in the MTX → ENBREL + MTX group (n=88) at Year 21
Footnotes:
  • * Disease activity score (DAS) 28 clinical remission is defined as a DAS <2.6 units. Calculation of DAS 28 utilizes tenderness scores (Ritchie Articular Index), swollen joint count, erythrocyte sedimentation rate (ESR), and visual analog scale (VAS) from a patient's general health assessment. The DAS 28 is a validated tool used in clinical trials and serves as the basis for the EULAR response criteria.1,3
  • The Year 2 population must have finished Year 1 and had data from at least 1 visit in Year 2.1
  • ** In this study, a modified DAS 44 was also utilized based on the 44-joint count (tender 44 and swollen 44) rather than 28 joints. DAS 44 clinical remission is defined as DAS <1.6 units.1,3

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 inhibited the progression of joint damage

View data

Patient support every day

Help your patients start and stay on ENBREL with help from dedicated nurses, online demos, and services to keep them on track.

View our everyday support
 
 
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