Miriam Santer, MD

Credit: southampton.ac.uk

Spironolactone can be a useful alternative to oral antibiotics for women with acne vulgaris, according to new findings, with improved outcomes compared to placebo.¹

These findings were the result of research designed to examine alternatives to antibiotics given increasing rates of resistance.² Spironolactone, a potassium sparing diuretic, was seen as one possible alternate method for reducing antibiotic use in patients with acne.

The research was authored by Miriam Santer, a professor of primary care research for the Faculty of Medicine at the University of Southampton in the UK. Santer and her team noted the paucity of randomized control trial (RCT) evidence before this study, with the largest trial having had only 34 participants.

“The Spironolactone for Adult Female Acne (SAFA) trial aimed to evaluate whether spironolactone improves acne in women with persistent facial acne compared with placebo, in addition to use of standard topical care,” Santer and colleagues wrote.

Background and Findings

The investigators for the SAFA trial conducted the study as a double-blind, randomized trial comparing spironolactone to a placebo in the treatment of facial acne in women. They designed it to assess the intervention's effectiveness in a real-life context, allowing participants to use topical treatments alongside the study medication.

Eligible participants were women aged 18 years or older with facial acne of at least 6 months' duration and sufficient severity. The research team used baseline assessments, face-to-face or remote follow-up meetings at 6 and then 12 weeks, and questionnaire-based follow-up at 24 to 52 weeks.

The team assigned the participants to receive either spironolactone or a placebo, beginning with a daily dose of 50 mg for 6 total weeks and then escalating to 100 mg if it was found to be tolerable. Treatment was set to continue for 24 weeks, during which participants were able to use their usual topical treatments.

Following 24 weeks, both groups entered an unblinded follow-up period of up to 52 weeks, during which they were allowed to seek further treatments. The investigators sought to evaluate the efficacy of spironolactone and its impact on participant-reported outcomes, while considering the challenges posed by the COVID-19 pandemic and allowing for flexible trial procedures and remote follow-up.

During the study period from June of 2019 to August of 2021, a total of 1,267 women were evaluated for their eligibility to participate in the trial. Among them, 410 women were randomly assigned to either the intervention arm of the study (n=201) or the control arm (n=209).

For the investigators’ primary analysis, 342 women (176 in the intervention group and 166 in the control group) were included. The average age at baseline was found to be 29.2 years with a standard deviation of 7.2.

Out of the 389 total study participants, 7% belonged to ethnicities other than White. In terms of acne severity, 46% were found to have had mild acne, 40% with moderate acne, and 13% with severe acne.

Overall, the investigators found that baseline mean Acne QoL symptom scores were reported as 13.2 for spironolactone and 12.9 for placebo, adding that at 12 weeks, the scores were 19.2 and 17.8, respectively.

The difference between the 2 study arms favored spironolactone (1.27, 95% CI 0.07 - 2.46) after adjusting for baseline variables. At 24 weeks, the scores were found to be 21.2 for spironolactone and 17.4 for placebo, with a difference of 3.45 (95% CI 2.16 - 4.75) after adjusting.

More participants in the spironolactone group reported showing acne improvement compared to the placebo group. At 12 weeks, the investigators found no major difference (72% vs. 68%, OR 1.16, 95% CI 0.70 - 1.91), but at 24 weeks, a substantial difference was observed (82% vs. 63%, OR 2.72, 95% CI 1.50 - 4.93).

Treatment success (IGA classified) at 12 weeks was noted in 19% of the 168 study participants given spironolactone and only 6% of the 160 receiving placebo (OR 5.18, 95% CI 2.18 - 12.28).

The research team added that adverse reactions were slightly more common in the spironolactone group, with a higher incidence of headaches reported (20% vs. 12%, P=0.02). No serious adverse reactions were reported in the study.

“Two ongoing trials of spironolactone in acne both chose a higher starting dose of spironolactone (100 mg and 150 mg) and the data for tolerability, adherence, and adverse effects will be interesting in these trials,” they wrote. “Outcomes of these might also provide opportunities for meta-analysis and greater power to examine effects within subgroups, particularly age, body mass index, and ethnicity.”

References

1. ^{Santer M, Lawrence M, Renz S, et al. Effectiveness of spironolactone for women with acne vulgaris (SAFA) in England and Wales: pragmatic, multicentre, phase 3, double blind, randomised controlled trial. BMJ. 2022;381:bmj-2022-074349. doi:10.1136/bmj-2022-074349.}
2. ^{Walsh TR, Efthimiou J, Dréno B, et al.Systematic review of antibiotic resistance in acne: an increasing topical and oral threat. Lancet Infect Dis2016;16:e23-33. doi:10.1016/S1473-3099(15)00527-7. pmid:26852728}