Authors' objectives: Acne is common, can cause significant impact on quality of life and is a frequent reason for long-term antibiotic use. Spironolactone has been prescribed for acne in women for many years, but robust evidence is lacking. To evaluate whether spironolactone is clinically effective and cost-effective in treating acne in women. Acne vulgaris (hereon ‘acne’) is common, can cause significant psychosocial impact and risks permanent scarring. Topical treatments are first line, but people commonly receive long courses of oral antibiotics, raising concerns regarding antimicrobial resistance. Spironolactone, a potassium-sparing diuretic, is widely used for other conditions, such as hypertension. Spironolactone has anti-androgenic properties and is prescribed by dermatologists to treat acne in women, but robust evidence of effectiveness is lacking. To evaluate whether spironolactone is clinically effective and cost-effective in treating persistent facial acne in women.

Authors' results and conclusions: Of 1267 women assessed for eligibility, 410 were randomised (201 intervention, 209 control), 342 in the primary analysis (176 intervention, 166 control). Mean age was 29.2 years (standard deviation 7.2) and 7.9% (28/356) were from non-white backgrounds. At baseline, Investigator’s Global Assessment classified acne as mild in 46%, moderate in 40% and severe in 13%. At baseline, 82.9% were using topical treatments. Over 95% of participants in both groups tolerated the treatment and increased their dose. Mean baseline Acne-Specific Quality of Life symptom subscale was 13.0 (standard deviation 4.7) across both groups. Mean scores at week 12 were 19.2 (standard deviation 6.1) for spironolactone and 17.8 (standard deviation 5.6) for placebo [difference favouring spironolactone 1.27 (95% confidence interval 0.07 to 2.46) adjusting for baseline variables]. Mean scores at week 24 were 21.2 (standard deviation 5.9) in spironolactone group and 17.4 (standard deviation 5.8) in placebo group [adjusted difference 3.77 (95% confidence interval 2.50 to 5.03) adjusted]. Secondary outcomes also favoured spironolactone at 12 weeks with greater differences at 24 weeks. Participants taking spironolactone were more likely than those taking placebo to report overall acne improvement at 12 weeks {72.2% vs. 67.9% [adjusted odds ratio 1.16 (95% confidence interval 0.70 to 1.91)]} and at 24 weeks {81.9% vs. 63.3% [adjusted odds ratio 2.72 (95% confidence interval 1.50 to 4.93)]}. Investigator’s Global Assessment was judged successful at week 12 for 31/201 (18.5%) taking spironolactone and 9/209 (5.6%) taking placebo [adjusted odds ratio 5.18 (95% confidence interval 2.18 to 12.28)]. Satisfaction with treatment improved in 70.6% of participants taking spironolactone compared with 43.1% taking placebo [adjusted odds ratio 3.12 (95% confidence interval 1.80 to 5.41)]. Adverse reactions were similar between groups, but headaches were reported more commonly on spironolactone (20.4% vs. 12.0%). No serious adverse reactions were reported. Taking account for missing data through multiple imputation gave an incremental cost per quality-adjusted life-year of £27,879 (adjusted) compared to placebo or £2683 per quality-adjusted life-year compared to oral antibiotics. Spironolactone resulted in better participant-reported and investigator-reported outcomes than placebo, with greater differences at week 24 than week 12. One thousand two hundred and sixty-seven potential patients were screened for eligibility, of whom 413 were randomised. Three participants were subsequently deemed to be screen failures, leaving 410 randomised participants [201 intervention (spironolactone) and 209 control (placebo)]. A total of 47.6% (195/410) participants were recruited through social media advertising, 19.8% (81/410) secondary care, 15.6% (64/410) primary care, 6.6% (27/410) community advertising, 6.6% (27/410) word of mouth and 3.9% (16/410) participants’ online search. Baseline characteristics Key participant characteristics were balanced at baseline. Mean age was 29.2 years [standard deviation (SD) 7.2; range 18–59]. Of 356 participants where ethnicity data were available, 92.1% (328/356) were white and 7.9% (28/356) were from non-white background. Mean body mass index (BMI) was 26.1 (SD 5.6). Approximately half of participants [213/410 (52.0%)] reported having acne for more than 5 years. 77/410 (18.7%) reported they had a diagnosis of PCOS or had baseline characteristics suggestive of PCOS. At baseline, 340/410 (82.9%) participants were using topical treatments, similar in both groups and remaining similar throughout the trial. Types of topical used were also similar across groups. At baseline, 172/410 (42.0%) participants were using hormonal treatments, of whom 123/172 (71.1%) were taking progesterone-only contraception and 49/172 (28.5%) were taking combined oral contraception or co-cyprindiol. Mean baseline Acne-QoL symptom subscale was 13.2 (SD 4.9) in the spironolactone group, 12.9 (SD 4.5) in the placebo group and 13.0 (SD 4.7) averaged across both groups. IGA was judged by clinicians to be 3 (mild) for 190/410 (46.3%), 4 (moderate) for 166 (40.5%) and 5 (severe) for 54 (13.2%) of participants. PGA was reported as almost clear by 4/410 (1.0%), mild by 86 (21.0%), moderate by 216 (52.7%), severe by 102 (24.9%) of participants and was not answered by 2 (0.5%) participants. Over 95% of participants in both groups tolerated the treatment and increased their dosage. Implications for health care Spironolactone provides a safe low-cost alternative to reduce use of oral antibiotics for women with persistent acne, suitable for use in primary care. Spironolactone treatment of up to 6 months is of greater benefit than shorter treatment duration.

Authors' methods: Pragmatic, parallel, double-blind, randomised superiority trial. Primary and secondary healthcare and community settings (community and social media advertising). Women aged 18 years and older with facial acne persisting for at least 6 months, judged to potentially warrant oral antibiotic treatment. Participants were randomised 1 : 1, using an independent web-based procedure, to either 50 mg/day spironolactone or matched placebo until week 6, increasing to 100 mg/day spironolactone or matched placebo until week 24. Participants continued usual topical treatment. Primary outcome was the adjusted mean difference in Acne-Specific Quality of Life symptom subscale score at 12 weeks. Secondary outcomes included Acne-Specific Quality of Life total and subscales; participant self-assessed improvement; Investigator’s Global Assessment; Participant’s Global Assessment; satisfaction; adverse effects and cost-effectiveness. Design This was a pragmatic, multicentre, participant-blinded and clinician-blinded, placebo-controlled randomised trial. Participants were recruited through primary care (search and mail-out or opportunistic recruitment), secondary care (opportunistic recruitment) and advertising, including community and social media advertising. Trial participants were randomised to receive either 50 mg spironolactone or matched placebo one tablet daily for the first 6 weeks and then two tablets daily (total 100 mg spironolactone or matched placebo) at (or after) week 6, providing the participant was tolerating any side effects. Treatment continued for 24 weeks in both groups. Participants in both groups could continue to use usual topical treatments throughout the trial but adherence to topicals was not promoted beyond usual care. Between baseline and week 12, participants were asked not to change their topical treatments and not to take oral treatments for acne such as oral antibiotics, hormonal treatments or isotretinoin. After week 12, participants could change usual acne care, including oral treatments, if needed. In both groups, spironolactone or placebo was stopped at week 24, participants were informed of their treatment allocation and entered an unblinded follow-up period up to week 52. After week 24, participants could seek any treatment from their usual clinical team, including spironolactone. Baseline assessment was carried out in secondary care to ensure standardisation of clinical assessments, as the Investigator’s Global Assessment (IGA) for acne is not commonly used in primary care and was an important secondary outcome. The baseline appointment included pregnancy test, blood test (to exclude renal impairment or raised serum potassium), participant photo to aid recall about changes in acne, and contraceptive counselling. Baseline visits were conducted by research nurses and/or dermatologists. Participants were followed up face-to-face (or by video call or telephone due to the COVID-19 pandemic) in secondary care at week 6 and week 12, with primary outcome assessment at week 12, and longer-term follow-up by questionnaires at week 24 and up to week 52. Participants eligible for inclusion were women aged 18 years or over: with facial acne vulgaris for at least 6 months acne of sufficient severity to warrant oral antibiotics, as judged by trial clinician; and with IGA ≥ 2 (mild or worse) women of childbearing potential at risk of pregnancy had to be willing to use their usual hormonal or barrier method of contraception for the first 6 months of the trial and for at least 4 weeks afterwards willing to be randomised sufficient English to self-complete acne-specific quality of life (Acne-QoL). Potential participants were excluded if: IGA acne grade was 0–1 (clear or almost clear) ever taken spironolactone taken oral isotretinoin within past 6 months taken oral antibiotics (lasting longer than 1 week) for acne within previous month started, stopped or changed hormonal contraception, co-cyprindiol or other hormonal treatment within past 3 months or planning to start, stop or change within the next 3 months intending to become pregnant in next 6 months spironolactone contraindicated: currently taking potassium-sparing diuretic, angiotensin-converting enzyme inhibitor, angiotensin II receptor blocker or digoxin hereditary problems of galactose intolerance, lactase deficiency or glucose–galactose malabsorption (as the spironolactone and placebo tablets contain lactose) androgen-secreting adrenal or ovarian tumour Cushing syndrome congenital adrenal hyperplasia estimated glomerular filtration rate below 60 ml/minute/1.73 m2 serum potassium level above upper limit of reference range for laboratory.

Project Status: Completed

URL for project: https://www.journalslibrary.nihr.ac.uk/programmes/hta/16/13/02

Year Published: 2024

URL for published report: https://www.journalslibrary.nihr.ac.uk/hta/MYJT6804

URL for additional information: English

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: United Kingdom

DOI: 10.3310/MYJT6804

Organisation Name: NIHR Health and Social Care Delivery Program

Contact Name: Rhiannon Miller

Contact Email: rhiannon.m@prepress-projects.co.uk