Improved clinical outcome and biomarkers in adults with papulopustular rosacea treated with doxycycline modified-release capsules in a randomized trial - 15/05/16
, Anna D. Holmes, PhD b, Yumiko Muto, BS a, Eugene Y. Huang, MD, PhD c, d, Norman Preston, PhD b, Warren J. Winkelman, MD, PhD b, Richard L. Gallo, MD, PhD aAbstract |
Background |
Patients with rosacea have increased amounts of cathelicidin and protease activity but their usefulness as disease biomarkers is unclear.
Objective |
We sought to evaluate the effect of doxycycline treatment on cathelicidin expression, protease activity, and clinical response in rosacea.
Methods |
In all, 170 adults with papulopustular rosacea were treated for 12 weeks with doxycycline 40-mg modified-release capsules or placebo in a multicenter, randomized, double-blind, placebo-controlled study. Clinical response was compared with cathelicidin and protease activity in stratum corneum samples obtained by tape strip and in skin biopsy specimens obtained from a random subset of patients.
Results |
Treatment with doxycycline significantly reduced inflammatory lesions and improved investigator global assessment scores compared with placebo. Cathelicidin expression and protein levels decreased over the course of 12 weeks in patients treated with doxycycline. Low levels of protease activity and cathelicidin expression at 12 weeks correlated with treatment success. Low protease activity at baseline was a predictor of clinical response in the doxycycline treatment group.
Limitations |
Healthy control subjects were not studied.
Conclusions |
Improved clinical outcome correlated with reduced cathelicidin and protease activity, supporting both the mechanism of doxycycline and the potential of these molecules as biomarkers for rosacea.
Le texte complet de cet article est disponible en PDF.Key words : biomarker, cathelicidin, doxycycline, kallikrein, matrix metalloproteinase, papulopustular, rosacea, serine protease
Abbreviations used : AE, BCA, CAMP, cDNA, GAPDH, hCAP18, IGA, KLK, MMP, mRNA, PEG, pTP
Plan
| Funding for clinical research study provided by Galderma Laboratories LP. |
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| Disclosure: Dr Holmes, Preston, and Winkelman were employees of Galderma Laboratories LP when this work was conducted. Drs Di Nardo, Huang, and Gallo, and Ms Muto have no conflicts of interest to declare. |
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| Investigator global assessment success rates for the intent-to-treat population were presented in poster form at the Society for Investigative Dermatology meeting on May 8-11, 2013 in Edinburgh, Scotland, the American Academy of Dermatology meeting on March 21-25, 2014 in Denver, CO, and the Winter Clinical meeting on January 17-22, 2014 in Waimea, HI. Investigator global assessment success rates for the subpopulation recently given a diagnosis of rosacea were presented in poster form at the Winter Clinical meeting on January 17-22, 2014 in Waimea, HI. |
Vol 74 - N° 6
P. 1086-1092 - juin 2016 Retour au numéro
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