Malignancy Rates
Malignancy rates similar over 10 years of continuous use1
Malignancy rates* (events/patient-year) from the ERA trial in the controlled portion and open-label extension1†
*Data are from clinical trials and include all Surveillance, Epidemiology, and End Results (SEER)-defined cancers (excluding nonmelanoma skin cancers, in situ carcinomas except bladder, and recurrent cancers) and comparisons are based on age and sex-matched cohorts.
†Observed on study or within 30 days after the last etanercept dose. The population for each year reflects all adult patients at the time of analysis who received at least one dose of study drug.
‡SIR = Standardized Incidence Ratio1
§In Year 1 of the COMET trial, safety was analyzed using the ITT population (N = 542), which was defined as all enrolled subjects in the trial who received at least 1 dose of the study drug. In Year 2, the ITT population (N = 411) was defined as all subjects who received at least 1 dose of study drug during Period 2.
- The ERA SIR was 0.99 (95% CI: 0.67-1.42), indicating that malignancy types and rates in the ERA trial were consistent with the general US population1
- Analysis of overall malignancy rates in ENBREL studies has demonstrated types and rates similar to those expected in the SEER database and suggests no increase over time2
- The rates observed in the LRA 10-year trial were consistent with the ERA trial. The total malignancy rates for the ERA 10-year trial (N = 558) and the LRA 10-year trial (N = 783) were 0.01 and 0.01 (events/patient-year), respectively1
- The malignancy rates in the COMET trial§, PRESTA study, and psoriatic arthritis pivotal trial were consistent with the rates shown above3
- Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with tumor necrosis factor (TNF) blockers, including ENBREL.
- In adult clinical trials of all TNF blockers, more cases of lymphoma were seen compared to control patients. The risk of lymphoma may be up to several-fold higher in RA and psoriasis patients. The role of TNF blocker therapy in the development of malignancies is unknown.
- Cases of acute and chronic leukemia have been reported in association with postmarketing TNF blocker use in RA and other indications. The risk of leukemia may be higher in patients with RA (approximately 2-fold) than the general population.
- Melanoma and non-melanoma skin cancer (NMSC) have been reported in patients treated with TNF blockers, including ENBREL. Periodic skin examinations should be considered for all patients at increased risk for skin cancer.
Study Descriptions
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The Early RA Trial and Open-label Extension Trial1-5:
- Multicenter, double-blind, double-dummy, phase 3 trial
- 632 MTX-naive patients with moderate to severe early 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 months
- This trial 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 end of year 2, patients switched to or continued twice-weekly ENBREL 25 mg subcutaneously
- Subjects could re-enroll in the continuing open-label portion of the study upon meeting specific predefined re-enrollment inclusion criteria
References
- Enbrel® (etanercept) Prescribing Information. Thousand Oaks, CA: Immunex Corporation; February 2011.
- Data on file, Amgen.
- Bathon JM, Martin RW, Fleischmann RM, et al. A comparison of etanercept and methotrexate in patients with early rheumatoid arthritis. N Engl J Med. 2000;343:1586-1593.
- Genovese MC, Bathon JM, Martin RW, et al. Etanercept versus methotrexate in patients with early rheumatoid arthritis: two year radiographic and clinical outcomes. Arthritis Rheum. 2002;46:1443-1450.
- Genovese MC, Bathon JM, Fleischmann RM, et al. Longterm safety, efficacy, and radiographic outcome with etanercept treatment in patients with early rheumatoid arthritis. J Rheumatol. 2005;32:1232-1242.
The Long-Standing RA Open-Label Extension Trial1,2:
- 714 adult patients with moderately to severely active RA (mean duration of disease = 12 years) who had previously inadequate response to one or more DMARDs and had received ENBREL either as monotherapy or in combination with MTX in various clinical trials
- Use of concomitant corticosteroids and/or NSAIDs was permitted during the study
- Most patients received ENBREL 25 mg twice weekly. Because all patients did not enter clinical trials at the same time, length of follow-up varies
- All 714 adult patients who received at least one dose of ENBREL were evaluated for safety. There was no active control or placebo arm in this open-label extension
References
- Moreland LW, Weinblatt ME, Keystone EC, et al. Etanercept treatment in adults with established rheumatoid arthritis: 7 years of clinical experience. J Rheumatol. 2006;33:854-861.
- Data on file, Amgen.