Frequency of Treatment Switching for Spironolactone Compared to Oral Tetracycline-Class Antibiotics for Women With Acne: A Retrospective Cohort Study 2010-2016

June 2018 | Volume 17 | Issue 6 | Original Article | 632 | Copyright © June 2018

John S. Barbieri MD MBA,a Juliana K. Choi MD PhD,a,b Nandita Mitra PhD,c David J. Margolis MD PhDa,c

aUniversity of Pennsylvania Perelman School of Medicine, Philadelphia, PA bDepartment of Veteran Affairs, Philadelphia, PA cDepartment of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Philadelphia, PA

both treatments had similar efficacy at 6 months, oral antibiotics were more efficacious at 3 months.38 Given this evidence that therapies that address the hormonal etiology of acne, such as oral contraceptive pills and spironolactone, may have slower onset of action when compared with oral antibiotics, oral tetracycline-class antibiotics may represent a more effective strategy for those looking for rapid improvement in their acne. Initial combination therapy with oral tetracycline-class antibiotics and spironolactone, with eventual tapering of the oral antibiotics and maintenance with spironolactone is another potential approach to consider in this population. Finally, it is important to consider that over 80% of adolescent women started on spironolactone as the index therapy are not prescribed a subsequent systemic agent within the first year of treatment and that the number needed to treat with an oral tetracycline-class antibiotic to prevent one instance of switching was 17, suggesting that for many adolescent women, spironolactone is an effective therapy for their acne.Many patients who were started on either spironolactone or oral tetracycline-class antibiotics were found to be receiving no systemic therapy at a later point during the first year of follow-up. This finding could be a result of periods of remission induced by the systemic agent, successful maintenance with topical therapies alone, discontinuation of therapy due to guideline recommendations (ie, limiting antibiotics to 3 months), or patients who stopped seeking care with systemic agents for their acne. While it is difficult to assess which factors were the greatest contributors, topical retinoids have been shown to maintain results following an initial treatment period with oral antibiotics, so it is possible that many of these patients started on either spironolactone or oral tetracycline-class antibiotics were subsequently able to maintain their improvement with topical therapies alone.39–41When compared to spironolactone, doxycycline hyclate was less likely to be switched than either minocycline or low-dose extended-release minocycline. Although these results should be interpreted with caution due to potential confounding by indication, these findings are consistent with a recent Cochrane review which found no evidence to support minocycline as being more effective than other tetracycline-class antibiotics.49 Given the potential safety concerns associated with minocycline, doxycycline may be preferable over minocycline for the treatment of acne vulgaris in this patient population.50,49This study has several strengths, including its large size with over 6,000 women treated with spironolactone. In addition, the broadly representative population included in the OptumInsight Clinformatics DataMart gives this study a high level of generalizability and the use of claims data minimizes potential loss to follow-up that could occur in a single-center observational study. The results of this study should be interpreted in the context of the study design. Any retrospective, claims based analysis has the potential for treatment selection bias. Since claims data lacks information on acne severity, we cannot exclude that patients treated with spironolactone may have a different acne severity than those treated with oral antibiotics. However, the sensitivity analysis demonstrates that plausible differences in acne severity between the groups are unlikely to have a significant effect on the primary outcome. While we are unable to assess the reasons for switching, and thus cannot measure therapeutic efficacy, since switching reflects some form of treatment failure, whether due to lack of efficacy, side-effects, cost, or other reasons, this outcome is likely a reasonable measure of clinical effectiveness in a real-world setting. Importantly, as used in the clinical practice scenarios captured in the dataset, spironolactone appears to be effective when compared with oral antibiotics. However, because of these potential source of bias, the results should be interpreted with caution when attempting to generalize to other patient populations. Although it is possible that we were unable to capture treatment failure among patients who were never seen in follow-up, given that moderate to severe acne is challenging to manage with over the counter agents alone, it is likely patients would continue to follow-up for subsequent care if their acne remained uncontrolled. Finally, we are not able to capture information about adverse effects associated with treatment, although prior studies have suggested that spironolactone is generally well tolerated.48,51,52In summary, spironolactone has similar rates of switching when compared to oral tetracycline-class antibiotics for the treatment of acne vulgaris, especially among adult women. As a result, spironolactone may represent an effective and safe alternative to oral antibiotics for women with moderate to severe acne. Increased utilization of spironolactone is a potential opportunity to improve antibiotic stewardship and reduce complications associated with antibiotic use. While ultimately large clinical trials are needed to determine the optimal management strategy for women with moderate to severe acne, these results provide additional support for the use of spironolactone in this patient population. 


The authors have no conflicts to declare. 


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John Barbieri MD MBA