The efficacy, safety, and tolerability of ivermectin compared with current topical treatments for the inflammatory lesions of rosacea: a network meta-analysis
Tóm tắt
Rosacea is a common chronic skin condition that manifests as recurrent inflammatory lesions. Long-term treatment is required to control symptoms and disease progression, with topical treatments being the first-line choice. Ivermectin 1 % cream is a new once-daily (QD) topical treatment for the inflammatory lesions of rosacea, and it is important to compare the efficacy, safety, and tolerability of ivermectin with other currently available topical treatments. A systematic literature review was performed from January 2011 to June 2015, with articles published prior to 2011 retrieved from a Cochrane review on rosacea. Randomized controlled trials of the topical treatment of adult patients with moderate-to-severe papulopustular rosacea were identified from electronic databases and trial registers, and supplemented with data from clinical study reports. Mixed treatment comparisons (MTCs) were conducted to compare different treatments according to Bayesian methodology. 57 studies were identified, with 19 providing data suitable for MTC. Ivermectin 1 % cream QD led to a significantly greater likelihood of success compared with azelaic acid 15 % gel twice-daily (BID) [relative risk (95 % credible interval): 1.25 (1.14–1.37)], and metronidazole 0.75 % cream BID [1.17 (1.08–1.29)] at 12 weeks. Ivermectin 1 % cream QD also demonstrated a significant reduction in inflammatory lesion count compared with azelaic acid 15 % gel BID [−8.04 (−12.69 to −3.43)] and metronidazole 0.75 % cream BID [−9.92 (−13.58 to −6.35)] at 12 weeks. Ivermectin 1 % cream QD led to a significantly lower risk of developing any AE or TRAE compared with azelaic acid 15 % gel BID [0.83 (0.71–0.97) and 0.47 (0.32–0.67), respectively]. Ivermectin 1 % cream QD appears to be a more effective topical treatment than other current options for the inflammatory lesions of rosacea, with at least an equivalent safety and tolerability profile, and could provide physicians and dermatologists with an alternative first-line treatment option.
Tài liệu tham khảo
Aksoy B, Altaykan-Hapa A, Egemen D, Karagoz F, Atakan N (2010) The impact of rosacea on quality of life: effects of demographic and clinical characteristics and various treatment modalities. Br J Dermatol 163(4):719–725
Baldwin HE (2010) A community-based study of the effectiveness of doxycycline 40 mg (30-mg immediate-release and 10-mg delayed-release beads) on quality of life and satisfaction with treatment in participants with rosacea. Cutis 86(5 Suppl):26–36
Beutner K, Calverese B (2005) A multi-center, investigator-blind clinical trial to assess the safety and efficacy of metronidazole gel 1 % as compared to metronidazole gel vehicle and metronidazole cream 1 % in the treatment of rosacea. J Am Acad Dermatol 52(Suppl. 3):10
Bjerke R, Fyrand O, Graupe K (1999) Double-blind comparison of azelaic acid 20 % cream and its vehicle in treatment of papulo-pustular rosacea. Acta Derm Venereol 79(6):456–459
Bohm D, Schwanitz P, Stock GS, Schmid-Ott G, Schulz W (2014) Symptom severity and psychological sequelae in rosacea: results of a survey. Psychol Health Med 19(5):586–591
Cribier B (2013) Rosacea under the microscope: characteristic histological findings. J Eur Acad Dermatol Venereol 27(11):1336–1343
Culp B, Scheinfeld N (2009) Rosacea: a review. P T 34(1):38–45
Dahl MV, Jarratt M, Kaplan D, Tuley MR, Baker MD (2001) Once-daily topical metronidazole cream formulations in the treatment of the papules and pustules of rosacea. J Am Acad Dermatol 45(5):723–730
Del Rosso JQ, Gallo RL, Tanghetti E, Webster G, Thiboutot D (2013a) An evaluation of potential correlations between pathophysiologic mechanisms, clinical manifestations, and management of rosacea. Cutis 91(3 Suppl):1–8
Del Rosso JQ, Thiboutot D, Gallo R, Webster G, Tanghetti E et al (2013b) Consensus recommendations from the American Acne & Rosacea Society on the management of rosacea, part 2: a status report on topical agents. Cutis 92(6):277–284
Draelos ZD, Elewski B, Staedtler G, Havlickova B (2013) Azelaic acid foam 15 % in the treatment of papulopustular rosacea: a randomized, double-blind, vehicle-controlled study. Cutis 92(6):306–317
Draelos Z, Elewski B, Harper J, Sand M, Staedtler G (2015) Randomized, phase III, double-blind, vehicle-controlled clinical trial to evaluate the safety and efficacy of 12 weeks of twice-daily azelaic acid foam, 15 % in papulopustular rosacea. Journal of the American Academy of Dermatology 72(5):AB59
Elewski BE, Fleischer AB Jr, Pariser DM (2003) A comparison of 15 % azelaic acid gel and 0.75 % metronidazole gel in the topical treatment of papulopustular rosacea: results of a randomized trial. Arch Dermatol 139(11):1444–1450
Elewski BE, Draelos Z, Dreno B, Jansen T, Layton A et al (2011) Rosacea—global diversity and optimized outcome: proposed international consensus from the Rosacea International Expert Group. J Eur Acad Dermatol Venereol 25(2):188–200
FDA (2014) SOOLANTRA™ (ivermectin) cream, 1 % for topical use. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/206255lbl.pdf
Fowler JF Jr (2007a) Combined effect of anti-inflammatory dose doxycycline (40-mg doxycycline, usp monohydrate controlled-release capsules) and metronidazole topical gel 1 % in the treatment of rosacea. J Drugs Dermatol 6(6):641–645
Fowler JF Jr (2007b) Combined effect of anti-inflammatory dose doxycycline (40-mg doxycycline, usp monohydrate controlled-release capsules) and metronidazole topical gel 1 % in the treatment of rosacea. J Drugs Dermatol 6(6):641–645
Galderma (2006) A randomized, six-arm, dose-ranging, multi-center, investigator-blind, placebo and active comparator controlled trial to select the dose and regimen of Ivermectin (CD5024) according to the dose-response relationship. RD.03.SRE.40027 CSR
Galderma (2014) CD5024 1 % cream versus metronidazole 0.75% cream in papulopustular rosacea (PPR) study (ATTRACT). RD.03.SRE.40173 CSR
Galderma (2015a) Galderma receives FDA approval of novel treatment option for rosacea patients. http://www.galderma.com/News/articleType/ArticleView/articleId/75/Galderma-Receives-FDA-Approval-of-Novel-Treatment-Option-for-Rosacea-Patients. Accessed Feb 2015
Galderma (2015b) Galderma announces positive outcome of European Decentralised Procedure for approval of Soolantra® (ivermectin) cream 10mg/g for rosacea patients. http://www.galderma.com/News/articleType/ArticleView/articleId/79/Galderma-Announces-Positive-Outcome-of-European-Decentralised-Procedure-for-Approval-of-SOOLANTRA-ivermectin-Cream-10mgg-for-Rosacea-Patients. Accessed April 2015
Gold LS, Kircik L, Fowler J, Tan J, Draelos Z (2014a) 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 13(3):316–323
Gold LS, Kircik L, Fowler J, Tan J, Draelos Z (2014b) Efficacy and safety of ivermectin 1 % cream in treatment of papulopustular rosacea: results of two randomized, double-blind, vehicle-controlled pivotal studies (18171 study). J Drugs Dermatol 13(3):316–323
Goldgar C, Keahey DJ, Houchins J (2009) Treatment options for acne rosacea. Am Fam Physician 80(5):461–468
Huynh TT (2013) Burden of disease: the psychosocial impact of rosacea on a patient’s quality of life. Am Health Drug Benefits 6(6):348–354
Koca R, Altinyazar HC, Ankarali H, Muhtar S, Tekin NS et al (2010) A comparison of metronidazole 1% cream and pimecrolimus 1 % cream in the treatment of patients with papulopustular rosacea: a randomized open-label clinical trial. Clin Exp Dermatol 35(3):251–256
Koch R, Wilbrand G (1999) Dark sulfonated shale oil versus placebo in the systemic treatment of rosacea. J Eur Acad Dermatol Venerol 12(Suppl. 32):S143–S144
Leyden JJ (2014) Randomized, phase 2, dose-ranging study in the treatment of rosacea with encapsulated benzoyl peroxide gel. J Drugs Dermatol 13(6):685–688
Maddin S (1999) A comparison of topical azelaic acid 20 % cream and topical metronidazole 0.75 % cream in the treatment of patients with papulopustular rosacea. J Am Acad Dermatol 40(6 Pt 1):961–965
Maier LE (2011) Rosacea: advances in understanding pathogenesis and treatment. Clin Invest 1(5):739–755
Marks R, Ellis J (1971) Comparative effectiveness of tetracycline and ampicillin in rosacea. A controlled trial. Lancet 2(7733):1049–1052
Moher D, Liberati A, Tetzlaff J, Altman DG (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med 151(4):264–269
Moore S (2015) Face values: global perceptions survey report. Galderma, Lausanne
NCT00617903 (2013) Exploration of safety and efficacy of AzA 15% foam twice a day in rosacea
NICE (2014) NICE DSU technical support document 2: a generalised modelling framework for pairwise and network meta-analysis of randomised controlled trials
Powell FC (2005) Clinical practice. Rosacea. N Engl J Med 352(8):793–803
Pye RJ, Burton JL (1976) Treatment of rosacea by metronidazole. Lancet 1(7971):1211–1212
SIGN Checklist (2015) SIGN checklist: critical appraisal of randomized controlled trials
Stein GL, Kircik L, Fowler J, Jackson JM, Tan J et al (2014) Long-term safety of ivermectin 1 % cream vs azelaic acid 15 % gel in treating inflammatory lesions of rosacea: results of two 40-week controlled, investigator-blinded trials. J Drugs Dermatol 13(11):1380–1386
Taieb A, Ortonne JP, Ruzicka T, Roszkiewicz J, Berth-Jones J et al (2015a) Superiority of ivermectin 1% cream over metronidazole 0.75 % cream in treating inflammatory lesions of rosacea: a randomized, investigator-blinded trial. Br J Dermatol 172(4):1103–1110
Taieb A, Ruzicka T, Berth-Jones J, Peirone MH, Jacovella J (2015b) Comparative efficacy and safety of ivermectin cream 1 % and metronidazole cream 0.75 % in the treatment of papulopustular rosacea. J Am Acad Dermatol 72(5):AB6
Tan JK, Girard C, Krol A, Murray HE, Papp KA et al (2002) Randomized placebo-controlled trial of metronidazole 1 % cream with sunscreen SPF 15 in treatment of rosacea. J Cutan Med Surg. 6(6):529–534
The National Rosacea Society (2015) Skincare: sun protection and moisturizers. Available at: https://www.rosacea.org/patients/skincare/moisturizer
Thiboutot D, Thieroff-Ekerdt R, Graupe K (2003) Efficacy and safety of azelaic acid (15 %) gel as a new treatment for papulopustular rosacea: results from two vehicle-controlled, randomized phase III studies. J Am Acad Dermatol 48(6):836–845
Thiboutot DM, Fleischer AB Jr, Del Rosso JQ, Graupe K (2008) Azelaic acid 15 % gel once daily versus twice daily in papulopustular rosacea. J Drugs Dermatol 7(6):541–546
Torok HM, Webster G, Dunlap FE, Egan N, Jarratt M et al (2005) Combination sodium sulfacetamide 10 % and sulfur 5 % cream with sunscreens versus metronidazole 0.75 % cream for rosacea. Cutis 75(6):357–363
van Zuuren EJ, Kramer S, Carter B, Graber MA, Fedorowicz Z (2011) Interventions for rosacea. Cochrane Database Syst Rev (3):CD003262
van Zuuren EJ, Fedorowicz Z, Carter B, van der Linden MM, Charland L (2015) Interventions for rosacea. Cochrane Database Syst Rev 4:CD003262
Wolf JE Jr, Del Rosso JQ (2007) The CLEAR trial: results of a large community-based study of metronidazole gel in rosacea. Cutis 79(1):73–80
Wolf JE Jr, Kerrouche N, Arsonnaud S (2006) Efficacy and safety of once-daily metronidazole 1 % gel compared with twice-daily azelaic acid 15 % gel in the treatment of rosacea. Cutis 77(4 Suppl):3–11