Pimecrolimus identifies a common genomic anti-inflammatory profile, is clinically highly effective in psoriasis and is well tolerated.

Abstract

The ascomycin macrolactam pimecrolimus is a novel inflammatory cytokine release inhibitor that so far has not been administered systemically to humans. In this phase I/II randomized double-blind, placebo-controlled, multiple rising dose proof of concept study psoriasis patients were treated with oral pimecrolimus or placebo. Gene profiling identified a common genomic profile with a downregulation of genes associated with inflammation but no changes in gene expression linked to drug-related side-effects. A steady state of pimecrolimus was reached after 5-10 d, Cmax, and area under the curve (0-24) was 54.5 ng per ml and 589.9 ng h per ml, respectively, at steady state at the highest dose. There was clear clinical efficacy in patients receiving 20 mg pimecrolimus twice daily and 30 mg twice daily with a reduction of Psoriasis Area and Severity Index by 60% and 75%, respectively. Histopatho logically and immunopathologically there was a reversion of the psoriatic phenotype towards normal. There were no notable clinical, laboratory, kidney function, or immunologic side-effects. We conclude that pimecrolimus taken orally is highly effective in a concentration-dependent manner in patients with psoriasis and on a short-term basis it is well tolerated and this is confirmed by its pharmacogenomic profile. The latter also indicates that pimecrolimus should be equally effective in other inflammatory skin diseases.

• Authors: Klemens Rappersberger, Michael Komar, Marie-Eve Ebelin, Graham Scott, Pascale Burtin, Gerard Greig, Jeanne Kehren, Salah-Dine Chibout, Andre Cordier, Wolfgang Holter, Leo Richter, Rainer Oberbauer, Anton Stuetz, Klaus Wolff
• Journal: The Journal of investigative dermatology (J Invest Dermatol) Vol. 119 Issue 4 Pg. 876-87 (Oct 2002) ISSN: 0022-202X [Print] United States
• PMID: 12406334 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• pimecrolimus
• Tacrolimus

Topics

• Adult
• Anti-Inflammatory Agents, Non-Steroidal (therapeutic use)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Female
• Follow-Up Studies
• Gene Expression Profiling
• Humans
• Male
• Middle Aged
• Psoriasis (drug therapy, genetics, immunology)
• Recurrence
• Tacrolimus (adverse effects, analogs & derivatives, pharmacokinetics, therapeutic use)