Serious and Opportunistic Infection Rates

Serious infection rates similar to MTX at 1 year, and consistent over 10 continuous years1,2*

Serious infection rates (events/patient-year) from the ERA study in the open-label extension
  • The SI rates in the LRA, COMET, TEMPO, and PsA studies were consistent with the rates shown above2-10
  • In patients receiving TNF-blocking agents, opportunistic infections, including TB, histoplasmosis, aspergillosis, candidiasis, coccidiodiomycosis, pneumocystosis, legionella, and listeriosis, have been reported11
  • Patients treated with ENBREL are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids or were predisposed to infection because of their underlying disease. ENBREL should not be initiated in the presence of sepsis, active infections, or allergy to ENBREL or its components. ENBREL should be discontinued if a patient develops a serious infection or sepsis.
Understanding the Data:
  • An opportunistic infection is an infection typically seen only in a host whose resistance is lowered12
  • In patients receiving TNF-blocking agents, opportunistic infections, including tuberculosis (TB), histoplasmosis, aspergillosis, candidiasis, coccidioidomycosis, legionella, listeriosis, and pneumocystosis, have been reported11
  • No cases of opportunistic infections were reported in the COMET study or Psoriatic Arthritis pivotal study7,9
  • Opportunistic infection rates were similar to controls in randomized controlled studies and overall clinical studies (RCT + OLE) in RA and psoriatic arthritis13
  • In 38 ENBREL clinical studies and 4 cohort studies in the US and Canada (N=17,696), no histoplasmosis infections were reported among patients treated with ENBREL. Nonetheless, postmarketing cases of serious and sometimes fatal fungal infections, including histoplasmosis, have been reported with TNF blockers, including ENBREL. Empiric antifungal therapy should be considered for patients who develop severe systemic illness11
  • * In the controlled portion, event rates were based on the definition of medically important infections (infections associated with hospitalization or intravenous [IV] antibiotics). For the long-term therapy, serious infections were defined as all serious adverse events that were infectious.2
  • These rates do not include TB.13
  • Included in this analysis were all adult patients (RA and psoriatic arthritis) who had received at least 1 dose of ENBREL in double-blind and open-label studies. For the double-blind portion of the RCTs, all events that occurred with onset dates between the first dose and the last dose were included. In the OLEs, all events with onset dates between the first dose and within 30 days after the last dose were included (within 15 days for some ex-US studies). Data as of May 2006. Data from the COMET study and PRESTA study were not included in these pooled analyses.13

Study Design


  • Multicenter, double-blind, double-dummy, Phase 3 study1,2
  • 632 MTX-naive patients with early moderately to severely active RA (≤3 years' duration) were randomized to receive twice-weekly ENBREL 25 mg (n=207), twice-weekly ENBREL 10 mg (n=208), or MTX (n=217). The mean duration of disease for these patients was 11 to 12 months1,2,4
  • This study became open-label and unblinded after all patients had completed 1 year of evaluation. Patients continued through 1 year of follow-up on the treatment to which they had been randomized. At the end of Year 2, patients switched to or continued twice-weekly ENBREL 25 mg subcutaneously1,2,5,6
  • Subjects could re-enroll in the continuing open-label portion of the study upon meeting specific predefined re-enrollment inclusion criteria2
  • Primary endpoints were area under the curve (AUC) for the numeric ACR score over 6 months and modified Total Sharp Score (mTSS) over 12 months4
  • In the OLE of ERA trial, MTX could be added to ETN if, after 1 year in the RCT, there was lack of efficacy
  • Of the 207 patient initially randomized to receive ENBREL 25 mg BIW at baseline, 79 patients did not receive MTX at any point during the OLE through 5 years3


  • Six-month, randomized, double-blind, placebo-controlled trial of patients with moderately to severely active RA (mean duration of disease: 12 years) who had a previous inadequate response to 1 or more DMARDs1,2
  • Open-label phase included 714 patients who had received ENBREL either as monotherapy or in combination with MTX in one of seven adult clinical trials: three placebo-controlled, randomized double-blind phase 2 or 3 trials; two phase 1 randomized dose-finding trials; two open-label trials. Exposure during the randomized controlled trial (RCTs) was included in the OLE1,2
  • Use of concomitant corticosteroids and/or NSAIDs was permitted during the study1,2
  • Most patients received ENBREL 25 mg twice weekly. Because all patients did not enter clinical studies at the same time, length of follow-up varies1,2
  • All 714 adult patients who received at least 1 dose of ENBREL were evaluated for safety. There was no active control or placebo arm in this open-label extension1,2
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

Introducing ENBREL Nurse Partners

Dedicated registered nurses are now available to give your patients the personal assistance
they need.

Here's how they can help

The experience of ENBREL

Evaluated in RA clinical studies over the past 20 years*

See our timeline history
*Initial clinical research in RA patients began in 1993.
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Phil Mickelson: A PsA patient's perspective
Disease activity vs. structural progression in RA
Treating Moderately Active RA
Rapid, Sustained Efficacy of ENBREL
Improving Outcomes in Psoriatic Arthritis
Achieving Clinical Remission
Efficacy of ENBREL Monotherapy for RA
A look back at 15 years