title: Cost-Effectiveness of Ivermectin 1% Cream in Adults with Papulopustular Rosacea in the United States.
abstract: BACKGROUND
  Papulopustular rosacea is a chronic skin disease involving central facial erythema in combination with papules and pustules. Papulopustular rosacea is treated with topical, systemic, or a combination of topical and systemic therapies. Currently approved topical therapies include azelaic acid gel/cream/foam twice daily (BID) and metronidazole cream/gel/lotion BID. Ivermectin 1% cream once daily (QD) is a new topical agent for the treatment of papulopustular rosacea that has been approved for the management of inflammatory lesions of rosacea and offers an alternative to current treatments.
  
  
  OBJECTIVE
  To evaluate the cost-effectiveness of ivermectin 1% cream QD compared with current topical treatments in order to understand the cost of adding ivermectin as a treatment option that would bring additional clinical benefit for adults with papulopustular rosacea in the United States.
  
  
  METHODS
  The cost-effectiveness of ivermectin 1% cream QD was compared with metronidazole 0.75% cream BID and azelaic acid 15% gel BID for adults in the United States with moderate-to-severe papulopustular rosacea using a Markov cohort state transition structure with 2 mutually exclusive health states (rosacea and no rosacea) and 5 phases. Patients could succeed or fail to respond to treatment and experience a relapse after treatment success. The model took a health care payer perspective (direct medical costs of topical and/or systemic therapy plus health care costs for physician and specialist visits) and used a 3-year time horizon. The model was run for a cohort of 1,000 patients. Costs (2014 U.S. dollars) and benefits (disease-free days and quality-adjusted life-years [QALYs]) were discounted at a rate of 3% per annum. Cost-effectiveness was determined by the incremental cost-effectiveness ratio (ICER) and measured in terms of incremental cost per QALY gained (estimated from health state utilities for patients with and without rosacea). Univariate and probabilistic sensitivity analyses (PSA) were conducted to assess the robustness of model outcomes.
  
  
  RESULTS
  Compared with metronidazole 0.75% cream BID, ivermectin 1% cream QD was associated with higher costs but provided greater clinical benefit, with an ICER of $13,211 per QALY gained. For a cohort of 1,000 patients, ivermectin 1% cream QD provided an additional 72,922 disease-free days (200 years) over a 3-year period compared with metronidazole 0.75% cream BID, leading to a lower cost per disease-free day for ivermectin 1% cream QD ($4.54) compared with metronidazole 0.75% cream BID ($4.85). Ivermectin 1% cream QD was associated with lower total costs and greater clinical benefit compared with azelaic acid 15% gel BID at year 3 and dominated this treatment. After 3 years, ivermectin 1% cream QD was associated with the lowest health care costs ($62,767 compared with $73,284 for metronidazole 0.75% cream BID and $77,208 for azelaic acid 15% gel BID), reflecting a 15% reduction in physician visit costs, when compared with metronidazole 0.75% cream BID, and almost a 20% reduction, when compared with azelaic acid 15% gel BID. The univariate sensitivity analyses indicated that the results are sensitive to the time horizon selected: the longer the time horizon, the more beneficial the results for ivermectin 1% cream QD relative to the comparators, although even at 1 year, ivermectin 1% cream QD dominated azelaic acid 15% gel BID. The PSA suggested that ivermectin 1% cream QD was the most likely treatment to be cost-effective at a willingness-to-pay threshold of $15,000 and above.
  
  
  CONCLUSIONS
  Ivermectin 1% cream QD had favorable incremental cost-effectiveness when compared with metronidazole 0.75% cream BID and dominated azelaic acid 15% gel BID in the treatment of papulopustular rosacea in the United States. Therefore, ivermectin 1% cream QD may be a good first-line treatment for papulopustular rosacea, providing additional clinical benefit at no or low additional cost.
  
  
  BACKGROUND
  This study was sponsored by Galderma Laboratories. The sponsor was involved in the design of the model structure but not in the collection of the data used to populate the model. Manuscript preparation was also funded by Galderma. Taieb is an investigator and advisor for Galderma. Gold is an investigator for Galderma. Feldman is a consultant and speaker for Galderma and has received grants from Galderma. Dansk and Bertranou received a research grant from Galderma to conduct this study. Dansk and Bertranou contributed to the design of the model structure, the sourcing and inputting of the data, and the interpretation of the results. Taieb, Feldman, and Gold contributed to the interpretation of the results. All authors reviewed draft versions of the manuscript and gave permission for the submission of the final version.
authors.affiliation: 1 Hôpital Saint-André, Service de Dermatologie et Dermatologie Pédiatrique, Bordeaux Cedex, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Taieb
authors.affiliation: 2 Department of Dermatology, Henry Ford Medical Center, Detroit, Michigan, United States.
authors.forename: Linda
authors.initials: L
authors.lastname: Stein Gold
authors.affiliation: 3 Department of Dermatology, Center for Dermatology Research, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Feldman
authors.affiliation: 4 PAREXEL Access Consulting, PAREXEL International, London, England.
authors.forename: Viktor
authors.initials: V
authors.lastname: Dansk
authors.affiliation: 4 PAREXEL Access Consulting, PAREXEL International, London, England.
authors.forename: Evelina
authors.initials: E
authors.lastname: Bertranou
mesh_terms: D000328:Adult; D003362:Cost-Benefit Analysis / Q000191:economics* / Q000379:methods; D004339:Drug Compounding; D005260:Female; D006801:Humans; D007559:Ivermectin / Q000008:administration & dosage / Q000737:chemistry / Q000191:economics*; D008297:Male; D008795:Metronidazole / Q000008:administration & dosage / Q000737:chemistry; D012393:Rosacea / Q000188:drug therapy* / Q000191:economics* / Q000453:epidemiology; D063465:Skin Cream / Q000008:administration & dosage / Q000737:chemistry / Q000191:economics*; D014481:United States / Q000453:epidemiology
chemical_list: D008795:Metronidazole; D007559:Ivermectin