Tools for Practice


#241 “Who’s the fairest of them all?”: Topical treatments for rosacea


CLINICAL QUESTION
Which topical agents provide the best patient reported improvements for rosacea?


BOTTOM LINE
For moderate-severe papulopustular rosacea, topical metronidazole, azelaic acid, and ivermectin have similar benefit with ~65-75% achieving patient reported improvement compared to ~40% with placebo over 2-3 months. In head-to-head trials, azelaic acid and ivermectin may be slightly better than metronidazole. Cost may assist choice.  



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EVIDENCE
Compared to placebo: 
  • Systematic review of randomized, placebo-controlled trials (RCTs) with patient orientated outcomes.1 Patients age ~50 years, ~65% female (unless stated). 
    • Metronidazole: Focusing on 2 similar RCTs of metronidazole 1% daily, 178 patients.2,3 After two months: 
      • Patient perceived symptom improvement (meta-analyzed by PEER):  
        • 75% versus 37% placebo; Number needed to treat (NNT)=3. 
    • Ivermectin 1% daily: 2 RCTs, 1371 patients.4 After three months: 
      • Good to excellent improvement (meta-analyzed by PEER): 
        • 68% versus 37% placebo; NNT=4. 
    • Azelaic acid 15-20% BID: 4 RCTs, 1226 patients.5-7 After three months: 
      • Good to excellent improvement:  
        • 63% versus 42% placebo; NNT=5.1 
Direct comparisons:  
  • Ivermectin 1% daily versus metronidazole 0.75% BID: 1 RCT; 962 patients.8 After 4 months: 
    • Good to excellent improvement: 
      • 86% ivermectin, 75% metronidazole; NNT=10.  
  • Azelaic acid 15% BID versus metronidazole 0.75% BID: 
    • Highest quality, largest RCT9; 251 patients, mean age 67. After 15 weeks: 
      • Good to excellent improvement:  
        • 78% azelaic acid, 64% metronidazole; NNT=8. 
      • 2 smaller, lower quality RCTs favour azelaic acid or show no difference.10,11 
Adverse events (primarily burning and stinging): 
  • Metronidazole, ivermectin, and azelaic acid: similar to placebo1.  
  • In one head-to-head trial,9 more patients on azelaic acid had adverse events than metronidazole (26% versus 7%). 
Limitations: most trials industry sponsored.  Context: 
  • Canadian guidelines first-line recommendations: topical metronidazole, azelaic acid, or ivermectin.12 
  • Estimated 90-day cost (Alberta)13:  
    • Azelaic acid 15% BID (FinaceaTM): $92  
    • Metronidazole 1% OD (MetrogelTM): $54 
    • Ivermectin 1% OD (RosiverTM): $220 
    • Metronidazole 0.75% BID (MetrogelTM): $440 
  • No clinical difference between 0.75% and 1% metronidazole.1 
  • Other topicals have less evidence1 or not currently recommended.12 
  • Oral medications reserved for severe symptoms or topical failure.12 
 


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Author(s):

  • Christina Korownyk MD CCFP
  • Michael R Kolber MD CCFP MSc
  • Paul Fritsch MD CCFP

1. Van Zuuren EJ, Fedorowicz Z, Carter B, et al. Cochrane Database Syst Rev. 2015;4:CD003262.

2. Bjerke JR, Nyfors A, Austad J, et al. Clin Trials J. 1989; 26(3):187-94.

3. Nielsen PG. Br J Dermatol. 1983; 108(3):327-32.

4. Stein L, Kircik L, Fowler J, et al. J Drugs Dermatol. 2014; 13(3):316-23.

5. Bjerke R, Fyrand O, Graupe KL. Acta Derm Venereol. 1999; 79:456-9.

6. Draelos ZD, Elewski B, Staedtler G, et al. Cutis. 2013; 92(6):306-17.

7. Thiboutot D, Thieroff-Ekerdt R, Graupe K. J Am Acad Derm. 2003; 48(6):836-45.

8. Taieb A, Ortonne JP, Ruzicka T, et al. Br J Dermatol. 2015; 172(4):1103-10.

9. Elewski BE, Fleischer AB, Pariser DM. Arch Dermatol. 2003; 139(11):1444-50.

10. Maddin S. J Am Acad Dermatol. 1999; 40(6):961-5.

11. Wolf JJ, Kerrouche N, Arsonnaud S. Cutis. 2006; 77(4 Suppl):3-11.

12. Asai Y, Tan J, Baibergenova A, et al. J Cut Med Surg. 2016; 20(5):432-45.

13. Calculations using data from Alberta Health Interactive Drug Benefit List. Available at: https://idbl.ab.bluecross.ca/idbl/load.do Accessed June 7, 2019.

Authors do not have any conflicts of interest to declare.