 |
 |
 |
 |
 |
 |
 |
|
|
|
|||||||||
|
|||||||||||
Post-Doctoral Regulatory Affairs/Drug Safety and Risk Management Fellow, School of Pharmacy, Biogen Idec/Massachusetts College of Pharmacy and Health Sciences, Worcester-Manchester, MA
Post-Doctoral Regulatory Affairs/Drug Safety and Risk Management Fellow, School of Pharmacy, Biogen Idec/Massachusetts College of Pharmacy and Health Sciences
Associate Professor of Pharmacy Practice, School of Pharmacy, Massachusetts College of Pharmacy and Health Sciences
Associate Professor of Pharmacy Practice, School of Pharmacy, Massachusetts College of Pharmacy and Health Sciences
Reprints: Dr. Scanlon, Massachusetts College of Pharmacy and Health Sciences, 19 Foster St., Worcester, MA 01608, fax 617/679-3170, james.scanlon1{at}mcphs.edu
OBJECTIVE: To systematically review the pharmacology, pharmacokinetics, clinical efficacy, and safety profile of ustekinumab to inform pharmacists and other healthcare professionals of this new biologic therapy for psoriasis.
DATA SOURCES: A search of PubMed/MEDLINE, EMBASE, and International Pharmaceutical Abstracts was performed through July 2009, limited to publications in English, using the search terms CNTO-1275, ustekinumab, interleukin-12, interleukin-23, and/or psoriasis to identify literature sources. References from the retrieved articles were also evaluated to identify relevant literature. An abstract from a Congress of the European Academy of Dermatology and Venereology and unpublished Phase 3 clinical trials in progress (using www.clinicaltrials.gov) were also reviewed. The Food and Drug Administration, European Medicines Agency, and Health Canada Web sites were used to retrieve product monographs, regulatory guidances, and advisory committee briefing packets.
STUDY SELECTION AND DATA EXTRACTION: All available studies relevant to the pharmacology, pharmacokinetics, and clinical safety/efficacy of ustekinumab for the treatment of psoriasis were included, with preference for human data.
DATA SYNTHESIS: Ustekinumab, an anti-interleukin-12/23 monoclonal antibody, achieved the primary endpoint of 75% reduction in the Psoriasis Area and Severity Index score in a large proportion of patients in the Phase 3 PHOENIX trials. Commensurate improvements were also seen in the Physician's Global Assessment and Dermatology Life Quality Index scores. These efficacy results were reproduced in the ACCEPT trial, demonstrating superiority of ustekinumab to etanercept. The frequency of adverse events was similar between ustekinumab and placebo; common adverse events reported included nasopharyngitis, upper respiratory tract infection, headache, arthralgia, cough, and injection site reactions. Phase 3 studies indicate that the optimal dosing appears to be 45 mg for patients weighing less than 100 kg or 90 mg for patients weighing more than 100 kg, with both doses administered subcutaneously. In these studies, the second dose was given 4 weeks after the first and then every 8-12 weeks thereafter, based upon response.
CONCLUSIONS: Ustekinumab, a promising new therapy, reduces the extent and severity of psoriasis and was well tolerated in clinical trials. Ongoing clinical trials will allow clinicians to further assess the efficacy/safety profile of this novel biologic.
Key Words: CNTO-1275, interleukin-12, interleukin-23, psoriasis, ustekinumab
Published Online, August 11, 2009. www.theannals.com, DOI 10.1345/aph.1M151
THIS ARTICLE IS APPROVED FOR CONTINUING EDUCATION CREDIT
ACPE
UNIVERSAL PROGRAM NUMBER: 407-000-09-018-H01-P
 |
 |
 |
 |
 |
 |
 |
