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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

Effectiveness of spironolactone for women with acne vulgaris (SAFA) in England and Wales: pragmatic, multicentre, phase 3, double blind, randomised controlled trial
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
Acne Vulgaris/drug therapy, Adult, Anti-Bacterial Agents/therapeutic use, Double-Blind Method, Female, Humans, Immunoglobulin A, Quality of Life, Spironolactone/adverse effects, Treatment Outcome, Wales
0959-8138
e074349
Santer, Miriam
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Lawrence, Megan
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Renz, Susanne M
4537317b-9305-464a-af38-5dd50ed70258
Eminton, Zina
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Stuart, Beth
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Sach, Tracey
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Pyne, Sarah
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Ridd, Mathew J.
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Muller, Ingrid
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Francis, N.A.
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Soulsby, Irene
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Thomas, Karen
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Permyakova, Natalia Vadimovna
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Little, Paul
1bf2d1f7-200c-47a5-ab16-fe5a8756a777
Muller, Ingrid
2569bf42-51bd-40da-bbfd-dd4dbbd62cad
Nuttall, Jacqueline
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Griffiths, Gareth
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Thomas, Kim S.
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Layton, Alison M.
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Santer, Miriam
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Lawrence, Megan
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Renz, Susanne M
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Eminton, Zina
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Stuart, Beth
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Sach, Tracey
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Pyne, Sarah
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Ridd, Mathew J.
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Muller, Ingrid
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Francis, N.A.
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Soulsby, Irene
35236c31-871e-4f3a-a814-3a7365f32316
Thomas, Karen
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Permyakova, Natalia Vadimovna
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Little, Paul
1bf2d1f7-200c-47a5-ab16-fe5a8756a777
Muller, Ingrid
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Nuttall, Jacqueline
154aec0a-05f2-4379-918e-9c36767fdc4c
Griffiths, Gareth
7fd300c0-d279-4ff6-842d-aa1f2b9b864d
Thomas, Kim S.
75e143ff-868e-47dc-b892-c9745a7e496a
Layton, Alison M.
5b851301-28e2-49f6-af30-a1bb7f35baa1

Santer, Miriam, Lawrence, Megan, Renz, Susanne M, Eminton, Zina, Stuart, Beth, Sach, Tracey, Pyne, Sarah, Ridd, Mathew J., Muller, Ingrid, Francis, N.A., Soulsby, Irene, Thomas, Karen, Permyakova, Natalia Vadimovna, Little, Paul, Muller, Ingrid, Nuttall, Jacqueline, Griffiths, Gareth, Thomas, Kim S. and Layton, Alison M. (2023) Effectiveness of spironolactone for women with acne vulgaris (SAFA) in England and Wales: pragmatic, multicentre, phase 3, double blind, randomised controlled trial. The BMJ, 381, e074349, [e074349]. (doi:10.1136/bmj-2022-074349).

Record type: Article

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

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Accepted/In Press date: 6 March 2023
e-pub ahead of print date: 16 May 2023
Published date: 16 May 2023
Additional Information: Publisher Copyright: © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
Keywords: Acne Vulgaris/drug therapy, Adult, Anti-Bacterial Agents/therapeutic use, Double-Blind Method, Female, Humans, Immunoglobulin A, Quality of Life, Spironolactone/adverse effects, Treatment Outcome, Wales

Identifiers

Local EPrints ID: 477069
URI: http://eprints.soton.ac.uk/id/eprint/477069
ISSN: 0959-8138
PURE UUID: 48359d72-8c81-475c-957f-e9ec42355252
ORCID for Miriam Santer: ORCID iD orcid.org/0000-0001-7264-5260
ORCID for Tracey Sach: ORCID iD orcid.org/0000-0002-8098-9220
ORCID for Ingrid Muller: ORCID iD orcid.org/0000-0001-9341-6133
ORCID for N.A. Francis: ORCID iD orcid.org/0000-0001-8939-7312
ORCID for Paul Little: ORCID iD orcid.org/0000-0003-3664-1873
ORCID for Ingrid Muller: ORCID iD orcid.org/0000-0001-9341-6133
ORCID for Gareth Griffiths: ORCID iD orcid.org/0000-0002-9579-8021

Catalogue record

Date deposited: 25 May 2023 16:44
Last modified: 12 Jul 2024 02:14

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Contributors

Author: Miriam Santer ORCID iD
Author: Megan Lawrence
Author: Susanne M Renz
Author: Zina Eminton
Author: Beth Stuart
Author: Tracey Sach ORCID iD
Author: Sarah Pyne
Author: Mathew J. Ridd
Author: Ingrid Muller ORCID iD
Author: N.A. Francis ORCID iD
Author: Irene Soulsby
Author: Karen Thomas
Author: Natalia Vadimovna Permyakova
Author: Paul Little ORCID iD
Author: Ingrid Muller ORCID iD
Author: Jacqueline Nuttall
Author: Kim S. Thomas
Author: Alison M. Layton

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