Long-term safety experience of ustekinumab in patients with moderate-to-severe psoriasis (Part I of II): results from analyses of general safety parameters from pooled Phase 2 and 3 clinical trials.

Abstract

BACKGROUND:

Ustekinumab targets interleukin (IL)-12 and IL-23 in the treatment of moderate-to-severe psoriasis.

OBJECTIVE:

To evaluate overall pooled study data to assess the safety profile of ustekinumab through 3 years of treatment.

METHODS:

Cumulative safety data were pooled from studies in 3117 ustekinumab-treated patients.

RESULTS:

During the placebo-controlled periods (Phase 2, PHOENIX 1, PHOENIX 2), rates of adverse events (AEs) were comparable among patients treated with placebo (50.4%), with ustekinumab 45 mg (57.6%), or with ustekinumab 90 mg (51.6%); similar findings were observed during the controlled period of the ACCEPT trial (etanercept: 70.0%; ustekinumab 45 mg: 66.0%; and ustekinumab 90 mg: 69.2%). Rates of serious AEs (SAEs) through the controlled periods were low and comparable among all groups (1.2% to 1.9%). Through 3 years, rates of AEs per 100 patient-years of follow-up (/100 patient-yrs) (45 mg: 305.2/100 patient-yrs; 90 mg: 305.9/100 patient-yrs) and SAEs (45 mg: 6.8/100 patient-yrs; 90 mg: 8.2/100 patient-yrs) were comparable between ustekinumab doses. No cases of demyelination or tuberculosis were reported in these trials. No dose response in rates of AEs, overall infections, or SAEs was apparent through 3 years. Rates of AEs, infections, SAEs, and AEs leading to study agent discontinuation remained generally stable or decreased over time.

LIMITATIONS:

Controlled periods did not extend beyond 12 to 20 weeks. Only 1247 of the 3117 ustekinumab-treated patients were treated for 2 or more years.

CONCLUSIONS:

The safety profile of continued ustekinumab exposure through up to 3 years is favorable and consistent with previous short-term reports.

• Authors: Mark Lebwohl, Craig Leonardi, Christopher E M Griffiths, Jörg C Prinz, Philippe O Szapary, Newman Yeilding, Cynthia Guzzo, Shu Li, Ming-Chun Hsu, Bruce Strober
• Journal: Journal of the American Academy of Dermatology (J Am Acad Dermatol) Vol. 66 Issue 5 Pg. 731-41 (May 2012) ISSN: 1097-6787 [Electronic] United States
• PMID: 21930328 (Publication Type: Clinical Trial, Phase II, Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Immunoglobulin G
• Receptors, Tumor Necrosis Factor
• Ustekinumab
• Etanercept

Topics

• Adult
• Aged
• Antibodies, Monoclonal (adverse effects, therapeutic use)
• Antibodies, Monoclonal, Humanized
• Dose-Response Relationship, Drug
• Double-Blind Method
• Drug Administration Schedule
• Drug-Related Side Effects and Adverse Reactions
• Etanercept
• Evaluation Studies as Topic
• Female
• Follow-Up Studies
• Humans
• Immunoglobulin G (adverse effects, therapeutic use)
• Male
• Middle Aged
• Psoriasis (diagnosis, drug therapy)
• Receptors, Tumor Necrosis Factor (therapeutic use)
• Risk Assessment
• Safety Management
• Severity of Illness Index
• Time Factors
• Treatment Outcome
• Ustekinumab