The SAFA study, funded by the National Institute for Health and Care Research (NIHR), is the first large-scale clinical trial to provide evidence that spironolactone is an effective treatment for the skin condition.

The results of the trial, led by GP Professor Miriam Santer from the University of Southampton and Dermatologist Professor Alison Layton from Harrogate and District NHS Foundation Trust and the Skin Research Centre at the University of York, and run by the Southampton Clinical Trials Unit, have been published in the British Medical Journal today (17 May).

It’s expected the results will change in the way acne in women is routinely treated, improve acne outcomes, and reduce the large amount of antibiotics currently prescribed for the condition.

A need for new treatments

Acne is very common, particularly in adolescence, and often clears with age. But almost a third of women continue to be affected in adulthood and this can be a huge physical and psychological burden to those who suffer from persistent outbreaks.

Topical treatments (creams and gels), available from a pharmacy or on prescription, are the first-line treatment for acne. They are effective for many people, but if they don’t work then GPs will often prescribe oral antibiotics to be used alongside the creams and gels. This can add to the growing burden of antibiotic resistance in the population.

“For several years, dermatologists have been prescribing a drug called spironolactone to treat severe acne,” says Professor Alison Layton, consultant dermatologist and co-lead of the SAFA trial.

“This is a cheap medication which has been used for decades in the treatment of high blood pressure. The drug also reduces the main hormone that leads to the development of acne.”

“However, previous studies of spironolactone for acne have been very small and there was no definitive proof that it actually worked.”

An effective treatment

The SAFA trial recruited over 400 women, aged over 18, with acne that had persisted for more than 6 months and where oral antibiotics would have normally been the next treatment. Half were randomly allocated to take spironolactone, while the other half were given a placebo, or dummy pill.

The women were asked to complete questionnaires on their acne and quality of life relating to the condition at the start of the trial and then at 12 and 24 weeks into their treatment.

“The results showed that the women taking spironolactone saw a significant improvement in their acne after 12 and 24 weeks compared to those on the placebo,” says Professor Miriam Santer, GP and co-lead of the trial.

“A significantly higher proportion of people also reported that they felt satisfied that their skin had been helped compared with those receiving placebo, and any side effects were uncommon and very minor. These results show that spironolactone could offer an alternative to antibiotics for many women with persistent acne to use alongside topical acne treatments.”

Making a real difference

Kelly Cornick, 39, began suffering with severe acne in her teens and since then has been prescribed various creams and antibiotics as well as the contraceptive pill to try and control her skin.

“Nothing seemed to work,” says Kelly. “It might go away for a while, but then it would flare up again. It was sore, almost like blisters. I would get thick, red, lumps all along my jawline and at its worst it spread up onto the rest of my face. If I knocked a spot, it would really hurt and would bleed for ages. It was just horrible.”

The mum-of-three from Dorset says it had a huge effect on her both physically but also psychologically.

“It was embarrassing. People would stare and you almost feel that they’re looking at you like you’re dirty and don’t wash properly. I think the worst thing for me was when one of my nieces said: ‘have you got chicken pox’. She was only about two and kids are always quite honest, but that’s how bad it looked. It used to get me down. I’m a confident person but my skin just took over how I felt a lot of the time.”

Kelly was told about the SAFA trial by her dermatologist and contacted the trial team at Poole Hospital.

“Initially I started on the lower dose and there was an improvement. I then went onto the higher dose and within about three months everything was gone, all the spots had disappeared.”

Since finishing the trial, Kelly has been able to stay on spironolactone and has now been acne-free for over two years.

“Knowing how much it’s helped me, I hope that other people will now be given this treatment as an option instead of just trying the antibiotics. I want people to be able to experience it, because everyone should feel confident and happy, and not have spots.”

Positive results

Professor Matthew Ridd, Co-Principal Investigator from the Centre for Academic Primary Care at the University of Bristol, said, “This was a unique trial, identifying potential participants from primary care and the community, and enrolling them at local hospitals, in our case the Bristol Royal Infirmary. There were also additional challenges due to the COVID-19 pandemic to contend with. Completing the study, and with a positive finding, is a great achievement for everyone involved.”

Professor Andrew Farmer, Director of NIHR’s Health Technology Assessment Programme, said: “The findings from this important trial provide compelling evidence which could help thousands of women affected by persistent acne. The treatment provides a valuable alternative to antibiotics and ensures clinicians can also better avoid the harms that can arise from antimicrobial resistance.

“High quality, independently funded research like this is crucial in providing evidence to improve health and social care practice and treatments.”

Professor Santer concludes: “We hope the publication of these results will mean more GPs and dermatologists feel confident to prescribe spironolactone as a treatment for acne. The drug is already included in treatment guidelines for persistent acne in the US and Europe, and we hope this trial will lead to a change in the UK guidelines.”

The SAFA trial was run by the Southampton Clinical Trials Unit. It was funded by a Health Technology Assessment grant from the National Institute for Health and Care Research (NIHR) and was sponsored by the University of Southampton.

Paper: Effectiveness of spironolactone for women with acne vulgaris (SAFA) in England and Wales: pragmatic, multicentre, phase 3, double blind, randomised controlled trial. Miriam Santer, Megan Lawrence, Susanne Renz, Zina Eminton, Beth Stuart, Tracey H Sach, Sarah Pyne, Matthew J Ridd, Nick Francis, Irene Soulsby, Karen Thomas, Natalia Permyakova, Paul Little, Ingrid Muller, Jacqui Nuttall, Gareth Griffiths, Kim S Thomas, Alison M Layton. Published in British Medical Journal. 17 May 2023.

Linked opinion piece: What do we know about prescribing spironolactone for acne? Miriam Santer. Published in the British Medical Journal. 17 May 2023.

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Watch the video interview with study participant, Kelly Cornick: