L. Kircik, Z. Draelos, Michael Gold, Neil Sadick, Neal Bhatia
{"title":"固定剂量克林霉素磷酸酯 1.2%/阿达帕林 0.15%/过氧化苯甲酰 3.1%凝胶治疗中重度痤疮:4 项临床试验比较","authors":"L. Kircik, Z. Draelos, Michael Gold, Neil Sadick, Neal Bhatia","doi":"10.25251/skin.8.supp.416","DOIUrl":null,"url":null,"abstract":"Introduction: Combination therapies targeting multiple processes of acne pathogenesis are recommended for most acne patients. A three-pronged approach using an antibiotic, retinoid, and antibacterial may also increase treatment efficacy versus monotherapy or dual-combination products. Clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1% (BPO) polymeric mesh gel (CAB) is the first fixed-dose, triple-combination topical approved by the FDA for the treatment of acne. The objective of this analysis was to compare treatment success and effect size of once-daily CAB with its three constituent dyad gels, branded adapalene 0.3%/BPO 2.5% gel, and vehicle across four clinical studies. \nMethods: Two phase 2 (NCT03170388, NCT04892706) and two phase 3 (NCT04214652, NCT04214639) double-blind, randomized, 12-week studies enrolled participants with moderate-to-severe acne. In all studies, treatment success at week 12 (defined as a ≥2-grade reduction from baseline in Evaluator’s Global Severity Score and clear/almost clear skin) was a co-primary endpoint. Other co-primary endpoints (reduction from baseline in inflammatory and noninflammatory lesions) are not shown here. Treatment-emergent adverse events (TEAEs) and cutaneous safety/tolerability were also assessed. A post hoc analysis of number needed to treat (NNT)—the number of patients who need to be treated with an intervention for one additional patient to achieve success versus vehicle—was performed to provide an additional measure of treatment effect and to indirectly compare data across studies. \nResults: Across studies, approximately half of CAB-treated participants achieved treatment success by week 12 (range: 49.6-52.5%) versus less than one-fourth with vehicle (range: 8.1%-24.9%; P<0.01, all) and less than one-third with component dyads or branded adapalene 0.3%/BPO 2.5% (range: 27.8%-32.9%; P≤0.001, all). Treatment success rates were significantly greater for all active treatments versus vehicle (P<0.01, all). NNT values for CAB (3-5) were lower (better) than for constituent dyads (5-6) or branded adapalene 0.3%/BPO 2.5% (7), further indicative of greater efficacy. TEAEs with CAB were mostly of mild-to-moderate severity. TEAE and discontinuation rates were similar or lower with CAB gel than with adapalene/BPO dyad gels. Mean cutaneous safety/tolerability scores with CAB gel were <1 (mild) at all timepoints. \nConclusions: CAB gel demonstrated significantly greater efficacy in the treatment of moderate-to-severe acne than dyad gels and branded adapalene 0.3%/BPO 2.5% gel, with approximately half of participants achieving clear/almost clear skin by 12 weeks with CAB. Due to acne pathogenesis, a triple-combination treatment may result in clinical success more often than two-ingredient combination products. \nFunding: Ortho Dermatologics.","PeriodicalId":22013,"journal":{"name":"SKIN The Journal of Cutaneous Medicine","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Fixed-Dose Clindamycin Phosphate 1.2%/Adapalene 0.15%/Benzoyl Peroxide 3.1% Gel for Moderate-to-Severe Acne: Comparison of 4 Clinical Trials\",\"authors\":\"L. Kircik, Z. Draelos, Michael Gold, Neil Sadick, Neal Bhatia\",\"doi\":\"10.25251/skin.8.supp.416\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Introduction: Combination therapies targeting multiple processes of acne pathogenesis are recommended for most acne patients. A three-pronged approach using an antibiotic, retinoid, and antibacterial may also increase treatment efficacy versus monotherapy or dual-combination products. Clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1% (BPO) polymeric mesh gel (CAB) is the first fixed-dose, triple-combination topical approved by the FDA for the treatment of acne. The objective of this analysis was to compare treatment success and effect size of once-daily CAB with its three constituent dyad gels, branded adapalene 0.3%/BPO 2.5% gel, and vehicle across four clinical studies. \\nMethods: Two phase 2 (NCT03170388, NCT04892706) and two phase 3 (NCT04214652, NCT04214639) double-blind, randomized, 12-week studies enrolled participants with moderate-to-severe acne. In all studies, treatment success at week 12 (defined as a ≥2-grade reduction from baseline in Evaluator’s Global Severity Score and clear/almost clear skin) was a co-primary endpoint. Other co-primary endpoints (reduction from baseline in inflammatory and noninflammatory lesions) are not shown here. Treatment-emergent adverse events (TEAEs) and cutaneous safety/tolerability were also assessed. A post hoc analysis of number needed to treat (NNT)—the number of patients who need to be treated with an intervention for one additional patient to achieve success versus vehicle—was performed to provide an additional measure of treatment effect and to indirectly compare data across studies. \\nResults: Across studies, approximately half of CAB-treated participants achieved treatment success by week 12 (range: 49.6-52.5%) versus less than one-fourth with vehicle (range: 8.1%-24.9%; P<0.01, all) and less than one-third with component dyads or branded adapalene 0.3%/BPO 2.5% (range: 27.8%-32.9%; P≤0.001, all). Treatment success rates were significantly greater for all active treatments versus vehicle (P<0.01, all). NNT values for CAB (3-5) were lower (better) than for constituent dyads (5-6) or branded adapalene 0.3%/BPO 2.5% (7), further indicative of greater efficacy. TEAEs with CAB were mostly of mild-to-moderate severity. TEAE and discontinuation rates were similar or lower with CAB gel than with adapalene/BPO dyad gels. Mean cutaneous safety/tolerability scores with CAB gel were <1 (mild) at all timepoints. \\nConclusions: CAB gel demonstrated significantly greater efficacy in the treatment of moderate-to-severe acne than dyad gels and branded adapalene 0.3%/BPO 2.5% gel, with approximately half of participants achieving clear/almost clear skin by 12 weeks with CAB. Due to acne pathogenesis, a triple-combination treatment may result in clinical success more often than two-ingredient combination products. \\nFunding: Ortho Dermatologics.\",\"PeriodicalId\":22013,\"journal\":{\"name\":\"SKIN The Journal of Cutaneous Medicine\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-07-23\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"SKIN The Journal of Cutaneous Medicine\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.25251/skin.8.supp.416\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"SKIN The Journal of Cutaneous Medicine","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.25251/skin.8.supp.416","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Fixed-Dose Clindamycin Phosphate 1.2%/Adapalene 0.15%/Benzoyl Peroxide 3.1% Gel for Moderate-to-Severe Acne: Comparison of 4 Clinical Trials
Introduction: Combination therapies targeting multiple processes of acne pathogenesis are recommended for most acne patients. A three-pronged approach using an antibiotic, retinoid, and antibacterial may also increase treatment efficacy versus monotherapy or dual-combination products. Clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1% (BPO) polymeric mesh gel (CAB) is the first fixed-dose, triple-combination topical approved by the FDA for the treatment of acne. The objective of this analysis was to compare treatment success and effect size of once-daily CAB with its three constituent dyad gels, branded adapalene 0.3%/BPO 2.5% gel, and vehicle across four clinical studies.
Methods: Two phase 2 (NCT03170388, NCT04892706) and two phase 3 (NCT04214652, NCT04214639) double-blind, randomized, 12-week studies enrolled participants with moderate-to-severe acne. In all studies, treatment success at week 12 (defined as a ≥2-grade reduction from baseline in Evaluator’s Global Severity Score and clear/almost clear skin) was a co-primary endpoint. Other co-primary endpoints (reduction from baseline in inflammatory and noninflammatory lesions) are not shown here. Treatment-emergent adverse events (TEAEs) and cutaneous safety/tolerability were also assessed. A post hoc analysis of number needed to treat (NNT)—the number of patients who need to be treated with an intervention for one additional patient to achieve success versus vehicle—was performed to provide an additional measure of treatment effect and to indirectly compare data across studies.
Results: Across studies, approximately half of CAB-treated participants achieved treatment success by week 12 (range: 49.6-52.5%) versus less than one-fourth with vehicle (range: 8.1%-24.9%; P<0.01, all) and less than one-third with component dyads or branded adapalene 0.3%/BPO 2.5% (range: 27.8%-32.9%; P≤0.001, all). Treatment success rates were significantly greater for all active treatments versus vehicle (P<0.01, all). NNT values for CAB (3-5) were lower (better) than for constituent dyads (5-6) or branded adapalene 0.3%/BPO 2.5% (7), further indicative of greater efficacy. TEAEs with CAB were mostly of mild-to-moderate severity. TEAE and discontinuation rates were similar or lower with CAB gel than with adapalene/BPO dyad gels. Mean cutaneous safety/tolerability scores with CAB gel were <1 (mild) at all timepoints.
Conclusions: CAB gel demonstrated significantly greater efficacy in the treatment of moderate-to-severe acne than dyad gels and branded adapalene 0.3%/BPO 2.5% gel, with approximately half of participants achieving clear/almost clear skin by 12 weeks with CAB. Due to acne pathogenesis, a triple-combination treatment may result in clinical success more often than two-ingredient combination products.
Funding: Ortho Dermatologics.