Efficacy and Safety of Ivermectin 1% Cream in Treatment of Papulopustular Rosacea: Results of Two Randomized, Double-Blind, Vehicle-Controlled Pivotal Studies

March 2014 | Volume 13 | Issue 3 | Original Article | 316 | Copyright © March 2014


Linda Stein Gold MD,a Leon Kircik MD,b Joseph Fowler MD,c Jerry Tan MD,d Zoe Draelos MD,e Alan
Fleischer MD,f Melanie Appell MD,g Martin Steinhoff MD,h Charles Lynde MD,i
Hong Liu MSc,j and Jean Jacovella MDk
on behalf of the Ivermectin Phase III Study Group

aHenry Ford Medical Center, Department of Dermatology, Detroit, MI
bDerm Research, PLLC, Louisville, KY
cDermatology Specialists Research, Louisville, KY
dWindsor Clinical Research, Inc., Windsor, ON, Canada
eDepartment of Dermatology, Duke University School of Medicine, Durham, NC
fDepartment of Dermatology, Wake Forest University Health Sciences, Winston, Salem, NC
gTotal Skin and Beauty Dermatology Center, PC, Birmingham, AL
hUniversity of California-San Francisco, San Francisco, CA
iLynderm Research, Inc., Markham, ON, Canada
jGalderma R&D, Cranbury, NJ
kGalderma R&D, Sophia Antipolis, France

REFERENCES

  1. Wilkin J, Dahl M, Detmar M, et al. Standard classification of rosacea: Report of the National Rosacea Society Expert Committee on the classification and staging of rosacea. J Am Acad Dermatol 2002; 46:584–587.
  2. Gupta MA, Gupta AK, Chen SJ, Johnson AM. Comorbidity of rosacea and depression: an analysis of the National Ambulatory Medical Care Survey and National Hospital Ambulatory Care Survey- Outpatient Department data collected by the U.S. National Center for Health Statistics from 1995 to 2002. Br J Dermatol 2005; 153(6):1176-81.
  3. Del Rosso JQ, Gallo RL, Tanghetti E, Webster G, Thiboutot D. An evaluation of potential correlations between pathophysiologic mechanisms, clinical manifestations, and management of rosacea. Cutis 2013; 91(3 Suppl):1-8.
  4. Del Rosso JQ, Gallo RL, Kircik L, et al. Why is rosacea considered to be an inflammatory disorder? The primary role, clinical relevance, and therapeutic correlations of abnormal innate immune response in rosacea-prone skin. J Drugs Dermatol 2012; 11:694-700.
  5. Steinhoff M, Buddenkotte J, Aubert J, et al. Clinical, cellular, and molecular aspects in the pathophysiology of rosacea. J Investig Dermatol Symp Proc 2011; 15:2-11.
  6. Forton F, Seys B. Density of Demodex folliculorum in rosacea: a casecontrol study using standardized skin-surface biopsy. Br J Dermatol 1993; 128(6):650-9.
  7. Karincaoglu Y, Bayram N, Aycan O, Esrefoglu M. The clinical importance of demodex folliculorum presenting with nonspecific facial signs and symptoms. J Dermatol 2004; 31(8):618-26.
  8. van Zuuren EJ, Kramer SF, Carter BR, Graber MA, Fedorowicz Z. Effective and evidence-based management strategies for rosacea: summary of a Cochrane systematic review. Br J Dermatol 2011; 165(4):760-81.
  9. Elewski BE. Results of a national rosacea patient survey: common issues that concern rosacea sufferers. J Drugs Dermatol 2009; 8(2):120-3.
  10. Ci X, Li H, Yu Q, Zhang X, Yu L, Chen N, et al. Avermectin exerts anti-inflammatory effect by downregulating the nuclear transcription factor kappa-B and mitogen-activated protein kinase activation pathway. Fundam Clin Pharmacol 2009; 23(4):449-55.
  11. Yanagihara K, Kadoto J, Kohno S. Diffuse panbronchiolitis- pathophysiology and treatment mechanisms. Int J Antimicrob Agents 2001; 18 Suppl 1:S83-7.
  12. Ianaro A, Ialenti A, Maffia P, Sautebin L, Rombolà L, Carnuccio R, et al. Anti-inflammatory activity of macrolide antibiotics. J Pharmacol Exp Ther 2000; 292(1):156-63.
  13. Campbell WC. History of avermectin and ivermectin, with notes on the history of other macrocyclic lactone antiparasitic agents. Curr Pharm Biotechnol 2012; 13(6):853-65.
  14. Forstinger C, Kittler H, Binder M. Treatment of rosacea-like demodicidosis with oral ivermectin and topical permethrin cream. J Am Acad Dermatol 1999; 41: 775-7.
  15. Trendelenburg M, Büchner S, Passweg J, Rätz Bravo AR, Gratwohl A. Disseminated scabies evolving in a patient undergoing induction chemotherapy for acute myeloblastic leukaemia. Ann Hematol 2001;80(2):116-8.
  16. Pariser DM, Meinking TL, Bell M, Ryan WG. Topical 0.5% ivermectin lotion for treatment of head lice. N Engl J Med 2012; 367(18):1687-93.
  17. Finlay AY, Khan GK. Dermatology Life Quality Index (DLQI) – a simple practical measure for routine clinical use. Clin Exp Dermatol 1994; 19(3): 210-6.
  18. Nicholson K, Abramova L, Chren MM, Yeung J, Chon SY, Chen SC. A pilot quality-of-life instrument for acne rosacea. J Am Acad Dermatol 2007; 57(2):213-21.
  19. Zhang X, Song Y, Ci X et al. Ivermectin inhibits LPS-induced production of inflammatory cytokines and improves LPS-induced survival in mice. Inflamm Res 2008; 57:524-9.
  20. Gerber PA, Buhren BA, Steinhoff M, Homey B. Rosacea: The cytokine and chemokine network. J Investig Dermatol Symp Proc 2011; 15(1):40-7.
  21. Wolstenholme AJ, Rogers AT. Glutamate-gated chloride channels and the mode of action of the avermectin/milbemycin anthelmintics. Parasitology 2005; 131 Suppl:S85-95.
  22. Damian D. Demodex infestation in a child with leukemia: treatment with ivermectin and permethrin. Int J Dermatol 2003; 42:724-6.
  23. Filho PA, Hazarbassanov RM, Grisolia AB et al. The efficacy of oral ivermectin for the treatment of chronic blepharitis in patients tested positive for Demodex spp. Br J Ophthalmol 2011; 95: 893-5.
  24. Powell FC. Rosacea and the pilosebaceous follicle. Cutis 2004; 74 (3 Suppl): 9-12.
  25. Marks R. The enigma of rosacea. J Dermatol Treat 2007; 18:326-8.
  26. Forton FMN. Papulopustular rosacea, skin immunity and Demodex: pityriasis folliculorum as a missing link. J Eur Acad Dermatol Venereol 2012; 26:19-28.
  27. Reinholz M, Ruzicka T, Schauber J. Cathelicidin LL-37: An antimicrobial peptide with a role in inflammatory skin disease. Ann Dermatol 2012; 24(2):126-135.
  28. Millikan L. Rosacea as an inflammatory disorder: a unifying theory? Cutis 2004; 73(suppl 1): 5-8.

AUTHOR CORRESPONDENCE

Linda Stein Gold MDLSTEIN1@hfhs.org
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