Integrated safety analysis: short- and long-term safety profiles of etanercept in patients with psoriasis.

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.