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

BMJ 2023; 381 doi: https://doi.org/10.1136/bmj-2022-074349 (Published 16 May 2023) Cite this as: BMJ 2023;381:e074349

Linked Opinion

What do we know about prescribing spironolactone for acne?

  1. Miriam Santer, professor of primary care research1,
  2. Megan Lawrence, senior medical statistician2,
  3. Susanne Renz, trial manager,2,
  4. Zina Eminton, senior trial manager2,
  5. Beth Stuart, professor of medical statistics and clinical trials1 3,
  6. Tracey H Sach, professor of health economics4,
  7. Sarah Pyne, senior research associate in health economics4,
  8. Matthew J Ridd, professor of primary health care5,
  9. Nick Francis, professor of primary care research6,
  10. Irene Soulsby, public contributor6,
  11. Karen Thomas, public contributor6,
  12. Natalia Permyakova, medical statistician2 7,
  13. Paul Little, professor of primary care research1,
  14. Ingrid Muller, associate professor1,
  15. Jacqui Nuttall, head of trial management, non-cancer2,
  16. Gareth Griffiths, Director2,
  17. Kim S Thomas, professor of applied dermatology research8,
  18. Alison M Layton, professor of dermatology9
  19. on behalf of the SAFA trial investigators
  1. 1Primary Care Research Centre, Faculty of Medicine, University of Southampton, Southampton, UK
  2. 2Southampton Clinical Trials Unit, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK
  3. 3Wolfson Institute of Population Health, Faculty of Medicine and Dentistry, Queen Mary University of London, Yvonne Carter Building, London, UK
  4. 4Health Economics Group, Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich, UK
  5. 5Population Health Sciences, Bristol Medical School, University of Bristol, Canynge Hall, Bristol, UK
  6. 6Primary Care Research Centre, School of Primary Care, Population Sciences and Medical Education, University of Southampton, Southampton, UK
  7. 7National Institute for Health and Care Research, Research Design Service South Central, Faculty of Medicine, University of Southampton, Southampton, UK
  8. 8Centre of Evidence Based Dermatology, School of Medicine, University of Nottingham, Applied Health Services Research Building, University Park, Nottingham, UK
  9. 9Skin Research Centre, Hull York Medical School, University of York, York, UK
  10. Correspondence to: M Santer m.santer{at}soton.ac.uk
  • Accepted 6 March 2023

Abstract

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

Footnotes

  • Contributors: MS, AML, BS, THS, MJR, NF, KST, PL, JN, and GG conceived the study idea and initial study design in response to a National Institute for Health and Care Research Health Technology Assessment call, with later input from KT, IS, ZE, SR, ML, NP, and SP. Specific advice was given by BS on trial design and medical statistics; and THS on health economic evaluation. Analyses were conducted by ML, NP, and BS. MS and BS are guarantors. All authors contributed to the drafting of this paper, led by MS, and approved the final manuscript. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted.

  • Funding: This study presents independent research funded by the National Institute for Health and Care Research under its Health Technology Assessment programme (16/13/02). The views expressed are those of the author(s) and not necessarily those of the National Health Service, the National Institute for Health and Care Research, or the Department of Health and Social Care. The University of Southampton was the research sponsor for this trial.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/. We declare no support from any organisation other than the National Institute for Health and Care Research for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work; no other relationships or activities that could appear to have influenced the submitted work. AML has served as advisor, consultant, and/or investigator for research (funded to institution) and/or received honoraria for unrestricted educational events from Almirall, Eucerin, Galderma, GSK, La Roche-Posay, LEO Pharma, L’Oréal, Mylan, Origimm, and Proctor and Gamble.

  • The lead author affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as originally planned and registered have been explained.

  • Dissemination to participants and related patient and public communities: The results of the study have been sent to research participants.

  • Provenance and peer review: Not commissioned; externally peer reviewed.

Data availability statement

Consent was not obtained from participants for data sharing but authors will consider reasonable requests to make relevant anonymised participant level data available via the Southampton Clinical Trials Unit Data Sharing Committee.

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