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    Rosacea treatments

    Dermatologists welcome antibiotics, α-adrenergic agonists and more

     

    Redness and rebound

    For erythematotelangiectatic rosacea (ETR), topical options include the α-adrenergic agonist brimonidine. However, said Dr. Harper, "We have found that in a portion of patients, it seems to worsen redness. We don't know why that happens." Rather than reverting to baseline levels, she said, redness temporarily increases – sometimes three to six hours after use, sometimes after the drug wears off (in approximately 12 hours). If rebound redness is going to occur, she said, it usually happens within the first two weeks of treatment.

    Strategies to reduce this side effect include using good skin care, including barrier repair, and getting any papulopustular rosacea (PPR) under control before starting the drug – ideally with small doses and gradually titrating upward, Dr. Harper added. She also suggested that patients test the treatment at times when slight redness won't hamper their work or social plans.

    To manage patient expectations regarding topical brimonidine, "Let people know that we believe 10% to 20% of people might experience some worsening of redness. The good news is, it disappears completely within 24 hours of medication use in most people."

    Unfortunately, she said that in her experience, susceptible patients will experience rebound redness as long as they use the medication. "That would be a place where we would turn to one of our other treatments, such as a vascular laser to help combat that redness." Another interesting option for background redness that resists other treatments is off-label Botox (onabotulinum toxin A, Allergan), she said. "I've had some success with that treatment in my own practice." Studies have demonstrated success with micro-droplet2 and intralesional techniques.3

    Also encouraging, she said, is the performance of topical ivermectin 1% cream in PPR. Theoretically, said Dr. Harper, it offers antimicrobial and anti-inflammatory effects. In phase 3 testing, the once-daily drug was better tolerated in the active treatment cohort. Although this group included twice as many patients as did the vehicle cohort (452 versus 231), only 24 patients in the treatment group experienced treatment-related adverse events, versus 25 patients in the vehicle group.4 At week 12, the treatment had reduced baseline mean inflammatory lesion count (30) by 20.5, versus 12 for placebo (P<0.01).

    Topical azelaic acid targets inflammation, bacteria, hyperkeratinization and pigmentation, said Dr. Harper. It also has been shown to inhibit cathelicidin, kallikrein 5 and serine protease activity.5 In a recent study, azelaic acid 15% foam reduced mean baseline inflammatory lesion count (21) by 13.2 per patient (versus 10.3 for vehicle; P<0.001) after 12 weeks' use.6

    "I use both topical ivermectin and azelaic acid regularly. Both are very effective and well-tolerated in rosacea," said Dr. Harper.

    On the horizon, another α-adrenergic agonist, oxymetazoline 1% cream, likely will earn FDA approval in early 2017, predicted Drs. Harper and Webster. Allergan submitted the drug for FDA approval in mid-2016 and expects its Prescription Drug User Fee Act date in the first half of 2017, according to the company.

    In phase 3 clinical trials, after one month of use, 41.9% of patients were satisfied or very satisfied 12 hours post-treatment (versus 24.8% of placebo-treated patients; P<0.001).7 Compared to brimonidine, said Dr. Harper, "It has a slightly different receptor selectivity. And it appears to have a slower onset of action and a good tolerability profile." Dr. Webster added that topical oxymetazoline has few if any side effects – "perhaps a little irritation."

    Finally, said Dr. Harper, "We always have patients for whom we must think outside the box and try other things," such as low-dose isotretinoin, which has shown efficacy when used twice or three times weekly.8

    Dr. Harper said, "Low-dose isotretinoin seems to work pretty well – particularly if people stay on it." In a recent study, 58% patients who stopped the treatment after four months relapsed at a median of 15 weeks off treatment.9 In rosacea, she said, "We don't get long-term remission as we do in acne. The beauty of using isotretinoin in acne is that recurrence rates are only 15% to 20%, at one year off treatment, sometimes longer. There's probably a role for isotretinoin in rosacea," particularly with long-term regimens at very low doses.

     

    Disclosures:

    Dr. Webster has been a consultant, researcher and/or advisor for Allergan, Dermira, Galderma, Valeant, Sienna, BiopharmX, Sol-Gel, Foamix, Almirall, Cutanea and Sun Pharmaceutical Industries Ltd.

    Dr. Harper has been a consultant, researcher and/or advisor for Allergan, Bayer, Galderma and Promius Pharma.

     

    References

    1. Arman ADemirseren DDTakmaz T. Treatment of ocular rosacea: comparative study of topical cyclosporine and oral doxycycline. Int J Ophthalmol. 2015;8(3):544-9.

    2. Park KY, Hyun MY, Jeong SY, Kim BJ, Kim MN, Hong CK. Botulinum toxin for the treatment of refractory erythema and flushing of rosacea. Dermatology. 2015;230(4):299-301.

    3. Dayan SHPritzker RNArkins JP. A new treatment regimen for rosacea: onabotulinumtoxinA. J Drugs Dermatol. 2012;11(12):e76-9.

    4. Stein LKircik LFowler J, et al. Efficacy and safety of ivermectin 1% cream in treatment of papulopustular rosacea: results of two randomized, double-blind, vehicle-controlled pivotal studies. J Drugs Dermatol. 2014;13(3):316-23.

    5. Coda ABHata TMiller J, et al. Cathelicidin, kallikrein 5, and serine protease activity is inhibited during treatment of rosacea with azelaicacid 15% gel. J Am Acad Dermatol. 2013;69(4):570-7.

    6. Draelos ZDElewski BStaedtler GHavlickova B. Azelaic acid foam 15% in the treatment of papulopustular rosacea: a randomized, double-blind, vehicle-controlled study. Cutis. 2013;92(6):306-17.

    7. Data on file. Allergan.

    8. Rademaker M. Very low-dose isotretinoin in mild to moderate papulopustular rosacea; a retrospective review of 52 patients. Australas J Dermatol. 2016 Jul 20. doi: 10.1111/ajd.12522.

    9. Sbidian EVicaut ÉChidiack H, et al. A randomized controlled trial of oral low-dose isotretinoin for difficult to treat papulopustular rosacea. J Invest Dermatol. 2016;136(6):1124-9.

    John Jesitus
    John Jesitus is a medical writer based in Westminster, CO.

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