Original article
Integrated safety analysis: Short- and long-term safety profiles of etanercept in patients with psoriasis

https://doi.org/10.1016/j.jaad.2011.07.040Get rights and content

Background

Multiple trials demonstrate the tolerability and safety of etanercept. However, there are limited data on etanercept tolerability in large populations of patients with psoriasis or with extended therapy.

Objectives

We sought to determine whether there is an increased safety risk associated with higher etanercept doses or with extended exposure in patients with psoriasis.

Methods

Integrated adverse event (AE) data from etanercept psoriasis trials were used to evaluate short-term (up to 12 weeks from controlled studies) and long-term (up to 144 weeks from uncontrolled extension studies) safety of etanercept (25 mg once weekly to 50 mg twice weekly). Long-term data were stratified by treatment regimens. Rates of noninfectious and infectious AE and standardized incidence ratios for malignancies were determined.

Results

In short-term analyses, rates of noninfectious and infectious AE and serious noninfectious and infectious AE were comparable between placebo and etanercept groups. In both short- and long-term analyses, there were no dose-related increases in these events. Cumulative event rates for serious infections were not significantly different across dose groups and over time. The standardized incidence ratios for malignancies excluding nonmelanoma skin cancers did not achieve statistical significance. There was no increase in overall malignancies with etanercept therapy compared with the psoriasis population. Lymphoma (n = 2 patients), demyelination (n = 2), congestive heart failure (n = 7), and opportunistic infection (n = 1) were rare.

Limitations

Study limitations include the rarity of some events and the resultant broad 95% confidence intervals.

Conclusions

In this integrated analysis, etanercept was well tolerated, and there were no signs of dose-related or cumulative toxicity over time.

Section snippets

Patients

Patients 18 years of age or older with moderate to severe plaque psoriasis involving 10% or more of body surface area were enrolled in 7 multicenter studies conducted in the United States, Canada, and Western Europe. Detailed inclusion and exclusion criteria for the individual studies have been published.9, 10, 11, 15, 24, 25, 26, 27 The institutional review boards and independent ethics committees at the participating study centers approved the study protocols, and patients gave written

Patient disposition

Of the 1965 patients in the short-term analyses, 160 received etanercept 25 mg QW, 415 received etanercept 25 mg BIW (50 mg QW), 670 received etanercept 50 mg BIW (100 mg QW), and 720 received placebo. The patient-years of exposure for the etanercept groups were 34.3 (25 mg QW), 101.1 (50 mg QW), and 147.2 (100 mg QW), and 156.3 for placebo. Because all patients in the short-term analyses had approximately 12 weeks of exposure, the treatment groups had the same values for median patient-years

Discussion

These integrated short- and long-term analyses demonstrated that etanercept was generally well tolerated in a large population of patients with psoriasis without dose-related or cumulative toxicities. The most common AEs reported in the short- and long-term analyses were not unexpected. The data were consistent with individual study results and with AE results from a previously reported integration of a subset of these studies,34 and a recent integrated safety report for etanercept across all

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    Disclosure: Dr Pariser has been a consultant and/or advisory board member for Abbott, Galderma, and Stiefel, and he has been investigator for Abbott, Amgen, Basilea, Dow, Eli Lilly, Galderma, Johnson and Johnson Consumer Products, Leo, MELA Sciences, Novo Nordisk, Peplin, Pfizer, Photocure, Shionogi, and Stiefel. Dr Leonardi has been a consultant for Abbott, Amgen, Centocor, and Pfizer; been an investigator for Abbott, Amgen, Celgene, Centocor, Genentech, Eli Lilly, Genzyme, Pfizer, Incyte, Schering-Plough, Novartis, Novo Nordisk, Vascular Biogenics, and Wyeth (Wyeth was acquired by Pfizer in October 2009); and served as a speaker for Abbott, Amgen, and Centocor. Dr Gordon has been a consultant and/or advisory board member for Abbott, Amgen, Celgene, Centocor, Lilly, Merck, and Medicis, and he has been an investigator for Amgen, Abbott, Centocor, and Celgene. Dr Gottlieb is a consultant and/or advisory board member for Abbott, Actelion, Alnylam, Amgen, Astellas, Beiersdorf, BIND Biosciences, Bristol Myers Squibb, Canfite, Centocor, Celgene, Cytokine Pharmasciences, Dermipsor, Immune Control, Incyte, Magen Biosciences, Merck, Novo Nordisk, Ono, Pfizer, PureTech, Schering, TEVA, and UCB, and has been a recipient of research/educational grants paid to Tufts Medical Center by Abbott, Amgen, Celgene, Centocor, Immune Control, Novartis, Novo Nordisk, Pfizer, and UCB. Dr Tyring has been an investigator and speaker for Amgen. Dr Papp has been a consultant, advisory board member, and investigator for Abbott, Amgen, Celgene, Centocor, Janssen Ortho, MedImmune, Pfizer, Schering-Plough, and Wyeth (Wyeth was acquired by Pfizer in October 2009), and has served as a speaker for Amgen, Abbott, Celgene, Janssen Ortho, Pfizer, Schering-Plough, and Wyeth (Wyeth was acquired by Pfizer in October 2009). Drs Li and Baumgartner are employees and stock holders of Amgen.

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    Copyright © 2011 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.