Table 6.
Summary of findings from this review, and recommendations for future research to fill the evidence gap: EPICOTa
| Element | Issues to consider | Status of research for this review and recommendations |
|---|---|---|
| Disease burden | Acne is the eighth most common disease globally, with peak prevalence in late adolescence. Acne in adult women is often recalcitrant to conventional medications, associated with a high degree of emotional distress and sometimes accompanied by hyperandrogenemia and/or other signs of peripheral hyperandrogenism, such as hirsutism and alopecia | |
| Evidence (E) | What is the current evidence? | This systematic review identified 10 RCTs and 21 case series that provided some evidence of the benefit and potential harms of oral spironolactone for acne in adult females. The most frequently reported outcome measure was physician-reported improvement in acne severity. Lesion counts were reported for two RCTs and none of the case series. Patient-assessed outcomes were reported for three RCTs and none of the case series Results from one RCT of crossover design at high risk of bias showed that spironolactone at a daily dose of 200 mg was significantly more effective than placebo against inflamed lesions (low-quality evidence, GRADE). Evidence for lower doses with respect to comparative efficacy versus placebo or active comparators was equivocal and of low or very low quality. There was some very-low-quality evidence that menstrual irregularities, the most common side effect observed in RCTs and case series, are dose-related and can be minimized by concomitant use of a combined oral contraceptive. Although serum potassium levels were measured in 7 RCTs and 12 case series, inadequate reporting meant that it was not possible to draw robust conclusions regarding the need for routine monitoring of hyperkalemia at any dose up to 200 mg/day in this patient population |
| Study type | What is the most appropriate study design to address the proposed question? | RCT |
| Population (P) | Diagnosis, disease stage, comorbidity, risk factors, gender, age, ethnic group, specific inclusion or exclusion criteria, clinical setting | Inclusion criteria: Premenopausal females aged 18 years and over with persistent or late-onset acne vulgaris Acne severity defined at baseline, e.g. at least moderate severity (IGA score of 3 on a 0–5 scale), with a minimum of 15 inflamed and 15 non-inflamed lesions on the face Women with PCOS can be included. In addition, women with additional signs of peripheral hyperandrogenism can also be included as long as the endocrinopathies listed below have been excluded Exclusion criteria: Pregnant or intending to become pregnant Androgen-secreting adrenal or ovarian tumor Cushing’s syndrome, late-onset congenital adrenal hyperplasia Unwilling to stop oral and topical anti-acne medications prior to the baseline visit Unwilling to use a barrier method of contraception for the duration of the study |
| Intervention (I) | Type, frequency, dose, duration, prognostic factor | Oral spironolactone at an initial dose of 25 or 50 mg/day, escalating as and if necessary to 100 mg/day after 6–8 weeks depending on response. Total treatment duration not <3 months, and preferably 6 months. It is recommended that concomitant topical therapy is not permitted for any study versus placebo (comparison one below) |
| Comparison (C) | Type, frequency, dose, duration, prognostic factor | In order of priority: 1. Matching placebo 2. An oral antibiotic of known magnitude of effect on acne 3. A combined oral contraceptive with low androgenicity of known magnitude of effect on acne |
| Outcome (O) | Which clinical or patient-related outcomes will the researcher need to measure, improve, influence, or accomplish? Which methods of measurement should be used? | 1. Change in the number of acne lesions (inflamed and non-inflamed) 2. Participant-assessed global improvement in acne severity using a Likert-like scale with photographic anchor at baseline 3. Change in HRQOL assessed using any validated or recognized quality-of-life instrument or as part of a validated patient-reported outcome measure 4. Proportion of participants who reported an adverse effect (putative drug-related adverse event) throughout the study period; number and type of adverse effects 5. Change in sebum excretion rate on the face using a validated method Note clinical outcomes and measures (1–3) may be subject to change as a result of ongoing work by the Acne Core Outcomes Research Network |
| Timelines | Time aspects of core elements: | |
| Age of population | 18 years and over; premenopausal | |
| Duration of intervention | At least 3 months, preferably 6 months | |
| Length of follow-up | At least 3 months, preferably 6 months (ideally with topical maintenance therapy) | |
| Time stamp (T) | Date of literature search or recommendation | November 2016 |
GRADE Grading of Recommendations Assessment, Development and Evaluation, RCTs randomized controlled trials, IGA Investigator’s Global Assessment, HRQOL health-related quality of life
aBrown et al. [125]