Effectiveness of spironolactone for women with acne vulgaris (SAFA) in England and Wales: pragmatic, multicentre, phase 3, double blind, randomised controlled trial.

OBJECTIVE: To assess the effectiveness of oral spironolactone for acne vulgaris in adult women. DESIGN: Pragmatic, multicentre, phase 3, double blind, randomised controlled trial. SETTING: Primary and secondary healthcare, and advertising in the community and on social media in England and Wales. PARTICIPANTS: Women (≥18 years) with facial acne for at least six months, judged to warrant oral antibiotics. INTERVENTIONS: Participants were randomly assigned (1:1) to either 50 mg/day spironolactone or matched placebo until week six, increasing to 100 mg/day spironolactone or placebo until week 24. Participants could continue using topical treatment. MAIN OUTCOME MEASURES: Primary outcome was Acne-Specific Quality of Life (Acne-QoL) symptom subscale score at week 12 (range 0-30, where higher scores reflect improved QoL). Secondary outcomes were Acne-QoL at week 24, participant self-assessed improvement; investigator's global assessment (IGA) for treatment success; and adverse reactions. RESULTS: From 5 June 2019 to 31 August 2021, 1267 women were assessed for eligibility, 410 were randomly assigned to the intervention (n=201) or control group (n=209) and 342 were included in the primary analysis (n=176 in the intervention group and n=166 in the control group). Baseline mean age was 29.2 years (standard deviation 7.2), 28 (7%) of 389 were from ethnicities other than white, with 46% mild, 40% moderate, and 13% severe acne. Mean Acne-QoL symptom scores at baseline were 13.2 (standard deviation 4.9) and at week 12 were 19.2 (6.1) for spironolactone and 12.9 (4.5) and 17.8 (5.6) for placebo (difference favouring spironolactone 1.27 (95% confidence interval 0.07 to 2.46), adjusted for baseline variables). Scores at week 24 were 21.2 (5.9) for spironolactone and 17.4 (5.8) for placebo (difference 3.45 (95% confidence interval 2.16 to 4.75), adjusted). More participants in the spironolactone group reported acne improvement than in the placebo group: no significant difference was reported at week 12 (72% v 68%, odds ratio 1.16 (95% confidence interval 0.70 to 1.91)) but significant difference was noted at week 24 (82% v 63%, 2.72 (1.50 to 4.93)). Treatment success (IGA classified) at week 12 was 31 (19%) of 168 given spironolactone and nine (6%) of 160 given placebo (5.18 (2.18 to 12.28)). Adverse reactions were slightly more common in the spironolactone group with more headaches reported (20% v 12%; p=0.02). No serious adverse reactions were reported. CONCLUSIONS: Spironolactone improved outcomes compared with placebo, with greater differences at week 24 than week 12. Spironolactone is a useful alternative to oral antibiotics for women with acne. TRIAL REGISTRATION: ISRCTN12892056.

Adverse Events in Isotretinoin Therapy: A Single-Arm Meta-Analysis.

Isotretinoin (ISO) is an oral prescription-only retinoid, well known for its acne-treating effect. However, it affects a substantial number of human cell types, causing a broad spectrum of adverse effects. The purpose of this study is to establish the isotretinoin therapy adverse events among human clinical trials and their prevalence. Two authors (J.K., J.L.) systematically performed the literature review and assessment from December 2021-February 2022. Three databases (PubMed, ClinicalTrials, and Cochrane Library) were searched using the following terms: "isotretinoin acne vulgaris" for published studies in English from 1980-2021. Finally, 25 randomized controlled clinical trials (RCTs) and five open-label clinical trials provided 3274 acne vulgaris suffering patients. Isotretinoin therapy affects almost all of the systems in the human body, causing numerous adverse events. However, they mainly concern mild mucocutaneous conditions (severe cases are rare) and represent individual responses to a drug. In addition, all adverse events are reversible and can be avoided by specific preparations.

C. acnes qPCR-Based Antibiotics Resistance Assay (ACQUIRE) Reveals Widespread Macrolide Resistance in Acne Patients and Can Eliminate Macrolide Misuse in Acne Treatment.

Background: Macrolides have been widely used to treat moderate-to-severe acne for more than 50 years. However, the prevalent antibiotic resistance of Propionibacterium acnes, along with the absence of clinically available resistance tests, has made macrolide misuse a frequent occurrence around the globe, with serious consequences. Objective: We developed Cutibacterium acnes quantitative PCR (qPCR)-based antibiotics resistance assay (ACQUIRE) to enable fast and accurate detection of C. acnes macrolide resistance in clinical settings, representing an opportunity to administer antibiotics more wisely and improve the quality of care. Methods: A cross-sectional observational study (n = 915) was conducted to probe into the macrolide resistance of C. acnes in patients with acne. Results: The high sensitivity of ACQUIRE enabled us to reveal a much higher C. acnes 23S recombinant DNA (rDNA) point mutation rate (52%) and thus a higher macrolide resistance (75.5%) compared to previous reports. Carriage of ermX gene was discovered on 472 (53%) subjects, which concurs with previous studies. Conclusion: The macrolide resistance of C. acnes is much higher than previously reported. Integrating ACQUIRE into acne treatment modalities may eliminate macrolide misuse and achieve better clinical improvements.

Biophysical and Biological Tools to Better Characterize the Stability, Safety and Efficacy of a Cosmeceutical for Acne-Prone Skin.

(1) Background: Acne is a widespread skin disease, especially among adolescents. Following the COVID-19 pandemic and the use of masks, the problem has been affecting a greater number of people, and the attention of the skin care beauty routine cosmetics has been focused on the "Maskne", caused by the sebum excretion rate (SER) that stimulates microbial proliferation. (2) Methods: the present study was focused on the rheological characterization and quality assurance of the preservative system of an anti-acne serum. The biological effectiveness (cytotoxicity-skin and eye irritation-antimicrobial, biofilm eradication and anti-inflammatory activity) was evaluated in a monolayer cell line of keratinocytes (HaCaT) and on 3D models (reconstructed human epidermis, RHE and human reconstructed corneal epithelium, HCE). The Cutibacterium acnes, as the most relevant acne-inducing bacterium, is chosen as a pro-inflammatory stimulus and to evaluate the antimicrobial activity of the serum. (3) Results and Conclusions: Rheology allows to simulate serum behavior at rest, extrusion and application, so the serum could be defined as having a solid-like behavior and being pseudoplastic. The preservative system is in compliance with the criteria of the reference standard. Biological effectiveness evaluation shows non-cytotoxic and irritant behavior with a good antimicrobial and anti-inflammatory activity of the formulation, supporting the effectiveness of the serum for acne-prone skin treatment.

Spironolactone for adult female acne (SAFA): protocol for a double-blind, placebo-controlled, phase III randomised study of spironolactone as systemic therapy for acne in adult women.

INTRODUCTION: Acne is one of the most common inflammatory skin diseases worldwide and can have significant psychosocial impact and cause permanent scarring. Spironolactone, a potassium-sparing diuretic, has antiandrogenic properties, potentially reducing sebum production and hyperkeratinisation in acne-prone follicles. Dermatologists have prescribed spironolactone for acne in women for over 30 years, but robust clinical study data are lacking. This study seeks to evaluate whether spironolactone is clinically effective and cost-effective in treating acne in women. METHODS AND ANALYSIS: Women (≥18 years) with persistent facial acne requiring systemic therapy are randomised to receive one tablet per day of 50 mg spironolactone or a matched placebo until week 6, increasing to up to two tablets per day (total of 100 mg spironolactone or matched placebo) until week 24, along with usual topical therapy if desired. Study treatment stops at week 24; participants are informed of their treatment allocation and enter an unblinded observational follow-up period for up to 6 months (up to week 52 after baseline). Primary outcome is the Acne-specific Quality of Life (Acne-QoL) symptom subscale score at week 12. Secondary outcomes include Acne-QoL total and subscales; participant acne self-assessment recorded on a 6-point Likert scale at 6, 12, 24 weeks and up to 52 weeks; Investigator's Global Assessment at weeks 6 and 12; cost and cost effectiveness are assessed over 24 weeks. Aiming to detect a group difference of 2 points on the Acne-QoL symptom subscale (SD 5.8, effect size 0.35), allowing for 20% loss to follow-up, gives a sample size of 398 participants. ETHICS AND DISSEMINATION: This protocol was approved by Wales Research Ethics Committee (18/WA/0420). Follow-up to be completed in early 2022. Findings will be disseminated to participants, peer-reviewed journals, networks and patient groups, on social media, on the study website and the Southampton Clinical Trials Unit website to maximise impact. TRIAL REGISTRATION NUMBER: ISRCTN12892056;Pre-results.

Oral isotretinoin treatment in patients with acne vulgaris during the COVID-19 pandemic: A retrospective cohort study in a tertiary care hospital.

BACKGROUND: Patients with acne vulgaris continue to present increasingly in dermatology outpatient clinics and seek treatment during the COVID-19 pandemic. As far as we know, the effect of isotretinoin on COVID-19 has not been studied before. AIM: We aimed to evaluate whether patients receiving oral isotretinoin are at increased risk of COVID-19 infection by comparing them with patients on topical treatment for acne vulgaris. METHODS: The data were collected retrospectively from a cohort of 267 acne vulgaris patients, who were under follow-up for acne vulgaris treatment during the pandemic period. RESULTS: Total of 227 patients (141 receiving isotretinoin treatment and 86 receiving topical treatment) were included of whom 29 patients had COVID-19 infection during acne vulgaris treatment. Fifteen (10.6%) patients were receiving oral isotretinoin and 14 (16.3%) were receiving topical acne treatment at the time of COVID-19 infection. The mean cumulative dose was 2340 ± 1988 mg at the time of COVID-19 infection. The mean elapsed time between the onset of isotretinoin treatment and positive PCR result for COVID-19 was 13.3 ± 10.3 weeks. Nine patients (64.3%) receiving isotretinoin treatment and 9 patients (60%) under topical treatment had loss of taste and smell during COVID-19 infection. Isotretinoin treatment was not found to be associated with a significant increased risk of getting COVID-19 (odds ratio, 0.671; 95% confidence interval, 0.247-1.823; P  = 0.434). CONCLUSION: As a conclusion, the results of this study encourage dermatologists and acne vulgaris patients to initiate oral isotretinoin treatment safely during the pandemic period.

Is systemic isotretinoin use a risk factor for coronavirus disease 2019 (COVID-19)?

AIM: To investigate whether acne treatment agent systemic isotretinoin causes susceptibility to COVID-19 disease. MATERIAL AND METHOD: Patients admitted to a single center due to acne between March 2020 and December 2020 were included. A retrospective analysis was conducted on the medical records of acne patients receiving systemic isotretinoin or topical treatments. The patients with PCR-confirmed SARS-CoV-2 infection were recorded. RESULTS: 302 patients who used isotretinoin and 329 patients who used topical treatment were included in the study. No statistically significant difference was found between the groups in terms of age (p = 0.151). It was found that of the 302 patients who used isotretinoin, 33 had PCR test for SARS-CoV-2 and two of these had PCR positivity, while of the 329 patients who received topical treatment, 45 had PCR test and five of these had PCR positivity. No statistically significant difference was found between the groups in terms of having SARS-CoV-2 positivity with PCR (p = 0.692). CONCLUSION: Susceptibility to COVID-19 disease was not observed in patients using systemic isotretinoin.