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Background/aims: Excessive use of antibiotics has led to development of antibiotic resistance and other antibiotic-associated complications. Dermatologists prescribe more antibiotics per clinician than any other major specialty, with much of this use for acne. Alternative acne treatments are available but are used much less often than antibiotics, at least partially because dermatologists feel that they are less effective. Spironolactone, a hormonal therapy with antiandrogen effects that can address the hormonal pathogenesis of acne, may represent a therapeutic alternative to oral antibiotics for women with acne. However, the comparative effects of spironolactone and oral antibiotics in the treatment of acne have not been definitively studied. The Spironolactone versus Doxycycline for Acne: A Comparative Effectiveness, Noninferiority Evaluation (SD-ACNE) trial aims to answer whether spironolactone, in addition to standard topical therapy, is noninferior to doxycycline (an oral antibiotic) for women with acne. Several interesting challenges arose in the development of this study, including determining acceptability of the comparative regimens to participating dermatologists, identifying data to support a noninferiority margin, and establishing a process for unblinding participants after they completed the study while maintaining the blind for study investigators., Methods: We present the scientific and clinical rationale for the decisions made in the design of the trial, including input from key stakeholders through a Delphi consensus process., Results: The Spironolactone versus Doxycycline for Acne: A Comparative Effectiveness, Noninferiority Evaluation trial (NCT04582383) is being conducted at a range of community and academic sites in the United States. To maximize external validity and inform clinical practice, the study is designed with broad eligibility criteria and no prohibition of use of topical medications. Participants in the trial will be randomized to receive either spironolactone 100 mg/day or doxycycline hyclate 100 mg/day for 16 weeks. The primary outcome is the absolute decrease in inflammatory lesion count, and we have established a noninferiority margin of four inflammatory lesions. Secondary outcomes include the percentage of participants achieving Investigator Global Assessment success, change in quality of life, and microbiome changes and diversity., Conclusions: The Spironolactone versus Doxycycline for Acne: A Comparative Effectiveness, Noninferiority Evaluation trial will have substantial implications for the treatment of acne and antibiotic stewardship. In addition, this study will provide important information on the effect of these systemic agents on the development of changes to the microbiome and antibiotic resistance in a healthy population of patients., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: J.S.B. has received consulting fees from Dexcel Pharma for work unrelated to this study.

Competing Interests: Conflicts of interest Dr Perry is a consultant for Rubrum Advising. Dr Barbieri is a consultant for Honeydew Care and Dexcel Pharma.

Competing Interests: Conflicts of interest Dr Barbieri has received consulting fees from Dexcel Pharma and Honeydew Care for work unrelated to the current submission. The remaining authors have no other conflicts to declare.

Importance: Isotretinoin is the only medical acne treatment capable of inducing acne remission; however, some patients experience acne relapse and require retrials of isotretinoin. There is a need to understand who is most at risk and how daily dose and cumulative dosage can influence outcomes., Objective: To assess rates of acne relapse and isotretinoin retrial and to identify associated factors among patients with acne who received an isotretinoin treatment course., Design, Setting, and Participants: This cohort study used data from the MarketScan commercial claims database from January 1, 2017, to December 31, 2020, to identify patients with acne who were 12 years or older and had received isotretinoin for 4 months or longer, with at least 1 year of continuous enrollment after completion of isotretinoin. Data analyses were performed from June 30, 2024, to August 1, 2024., Main Outcomes and Measures: Multivariable Cox proportional hazards regression was used to quantify associations of patient demographic and treatment characteristics with acne relapse and isotretinoin retrial., Results: A total of 19 907 patients (mean [SD] age, 20.6 [7.8] years; 10 504 females [52.8%]) were included, among whom 4482 (22.5%) had acne relapse and 1639 (8.2%) had isotretinoin retrial. Female sex (hazard ratio [HR], 1.43; 95% CI, 1.35-1.52) was significantly associated with increased rates of acne relapse, and isotretinoin cumulative dosage (mg/kg) was associated with a decreased rate of acne relapse (HR, 0.996; 95% CI, 0.995-0.997). Furthermore, daily dose was not associated with decreased risk of acne relapse or isotretinoin retrial among those with conventional and high cumulative dosages. Female sex (HR, 0.68; 95% CI, 0.62-0.76) and isotretinoin cumulative dosage (HR, 0.99; 95% CI, 0.98-0.99) were associated with decreased rates of isotretinoin retrial. Stratification by cumulative dosage indicated that higher cumulative dosage was associated with decreased rates of retrial among patients with low (<120 mg/kg) and conventional (120-220 mg/kg), but not high (>220 mg/kg) cumulative dosage. Maximum daily dose (mg/kg/d) was not negatively associated with acne relapse or isotretinoin retrial in patients with cumulative dosage of 120 mg/kg or more., Conclusions and Relevance: The findings of this cohort study suggest that higher cumulative dosage may potentially reduce risk of acne relapse and isotretinoin retrial. Furthermore, daily dose was not associated with decreased risk of the outcomes for conventional and high cumulative dosage; therefore, daily dosing could be individualized to patient goals and preferences.

Competing Interests: Conflicts of interest Dr Cohen serves on a data and safety monitoring board for Advarra and has served as a consultant for Novartis, Takeda, and GSK. Dr Barbieri has received consulting fees from Dexcel Pharma and Honeydew Care for work unrelated to the present submission. Authors Lowry and Nock have no conflicts of interest to declare.

Although many treatments are available for acne, these can be limited by lack of effectiveness, patient tolerance and adherence, and accessibility. This review provides a comprehensive summary of the latest developments in acne management, exploring a range of topical, systemic, and procedural treatments. The mechanisms of action, pivotal trial data, and potential role in clinical practice are reviewed for emerging therapies such as 1726 nm laser, sarecycline, clascoterone, trifarotene, minocycline foam, and fixed-dose combination topicals. The clinical pipeline is also summarized. In addition, opportunities to improve the patient experience with spironolactone and isotretinoin are discussed., Competing Interests: Disclosure Dr J.S. Barbieri has received consulting fees from Dexcel pharma., (Copyright © 2024 Elsevier Inc. All rights reserved.)