Clinical question
Which topical agents provide the best patient-reported improvements in rosacea?
Bottom line
For moderate to severe papulopustular rosacea, topical metronidazole, azelaic acid, and ivermectin have similar benefit, with about 65% to 75% of patients reporting improvement compared with about 40% of patients using placebo over 2 to 3 months. Head-to-head trials show that azelaic acid and ivermectin might be slightly better than metronidazole. Cost might assist choice.
Evidence
A systematic review of RCTs of treatments versus placebo with patient-oriented outcomes1 showed the following:
- In a meta-analysis by the PEER (Patients, Experience, Evidence, Research) Group of 2 similar RCTs of 178 patients using daily 1% metronidazole,2,3 patient-perceived symptom improvement after 2 months was 75% versus 37% with placebo (number needed to treat [NNT] = 3).
- In a meta-analysis by the PEER Group of 2 RCTs of 1371 patients,4 patients using daily 1% ivermectin showed good to excellent improvement after 3 months (68% vs 37% with placebo; NNT = 4).
- In 4 RCTs of 1226 patients,5–7 twice-daily 15% to 20% azelaic acid showed good to excellent improvement after 3 months1 (63% vs 42% with placebo; NNT = 5).
Daily 1% ivermectin versus twice-daily 0.75% metronidazole in 1 RCT of 962 patients8 showed good to excellent improvement after 4 months (86% with ivermectin and 75% with metronidazole; NNT = 10).
In the highest-quality, largest RCT9 of 251 patients, twice-daily 15% azelaic acid versus twice-daily 0.75% metronidazole showed good to excellent improvement after 15 weeks (78% with azelaic acid and 64% with metronidazole; NNT = 8).
Adverse events (primarily burning and stinging) for metronidazole, ivermectin, and azelaic acid were similar to placebo.1 In 1 trial,9 more patients using azelaic acid had adverse events than those using metronidazole (26% vs 7%).
Limitations: Most trials were industry sponsored.
Context
Canadian guidelines’ first-line recommendations are for topical metronidazole, azelaic acid, or ivermectin.10
The estimated 90-day costs in Alberta are as follows11:
-$92 for twice-daily 15% azelaic acid,
-$54 for daily 1% metronidazole,
-$220 for daily 1% ivermectin, and
-$440 for twice-daily 0.75% metronidazole.
There is no clinical difference between 0.75% and 1% metronidazole.1
Other topical treatments have less evidence for their use1 or are not currently recommended.10
Oral medications are reserved for severe symptoms or topical treatment failure.10
Implementation
Recently recommended diagnostic criteria for rosacea consider persistent centrofacial erythema or facial skin thickening (most commonly on the nose) independently diagnostic for rosacea. Additional major (eg, papules, pustules, and telangiectasias) and minor (eg, stinging sensation) features might assist with the diagnosis.12 Observational studies find that triggers (most commonly reported: sun exposure, stress, hot weather, wind, and alcohol use) might exacerbate rosacea.13 Until evidence to the contrary is found, avoidance of these potential triggers seems reasonable.
Notes
Tools for Practice articles in Canadian Family Physician are adapted from articles published on the Alberta College of Family Physicians (ACFP) website, summarizing medical evidence with a focus on topical issues and practice-modifying information. The ACFP summaries and the series in Canadian Family Physician are coordinated by Dr G. Michael Allan, and the summaries are co-authored by at least 1 practising family physician and are peer reviewed. Feedback is welcome and can be sent to toolsforpractice{at}cfpc.ca. Archived articles are available on the ACFP website: www.acfp.ca.
Footnotes
Competing interests
None declared
The opinions expressed in Tools for Practice articles are those of the authors and do not necessarily mirror the perspective and policy of the Alberta College of Family Physicians.
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