irregularities, breast tenderness, and gynecomastia, and may block the masculinizing effects of testosterone therapy.1,33 Considering the clinical and management gap in acne treatment, the authors recognize an unmet need for FDA-approved treatments that can safely address all key components of acne in a wide variety of patients (Table 1).
Guideline Limitations
Despite being developed based on the best available evidence, the current guidelines rely on studies that used different study designs, definitions of acne, and acne severity grading systems.1 Most acne clinical trials did not specifically include vulnerable patient groups requiring additional considerations with regard to the benefits and risks of acne medications, and therefore, these special populations, including patients who are menopausal, lactating, pregnant, or receiving androgen therapy, are not adequately represented in the current guidelines. Truncal acne is not specifically discussed in the guidelines despite 30% to 60% of patients with facial acne having truncal involvement as well.34-36 The skin on the trunk has different characteristics from facial skin, and different treatment recommendations could be more appropriate.37 The guidelines also lack a dedicated section discussing novel therapies1 and are therefore behind clinical practice and the present state of knowledge. Although many of these therapies are in various stages of development and lack high-quality evidence, the publication of a special issue of interim guidelines entirely dedicated to the introduction of new treatment options could be highly beneficial to increase practitioners' awareness.
Considerations for Healthcare Providers
The panel members noted that treatment of acne is challenging and that many factors influence treatment choices in addition to treatment guidelines and practitioners' clinical experience. These include sex (as systemic oral hormonal therapies cannot be used in male and transmasculine patients), skin sensitivity, skin type (ie, dry, oily vs nonoily, and phototype), anatomic sites affected, sebum production, presence of scarring, family history, underlying pathophysiology, patients' quality-of-life impact, patients' prior treatments, and special populations (ie, people who are menopausal, lactating, or pregnant; people with menstruation-associated acne; adolescents younger than 11 years of age; children below 8 years of age; and patients receiving testosterone). The panel has the following additional recommendations for healthcare providers:
Awareness That All Acne Is Fundamentally Hormone-Driven
A common misperception among practitioners is the belief that "hormonal" acne is limited to women, despite all acne having a hormonal basis. Healthcare practitioners should be aware that acne is often hormone-driven in male patients and in patients receiving exogenous androgen therapy, regardless of their gender.33
Clascoterone: Evaluating Clinical Success
Ongoing Education on New Treatment Options
The authors note that education regarding acne therapy about medications starts early in residency and is dependent on the knowledge base of the attending physicians and exposure to new pharmaceutical options. In the authors' experience, education is important to ensure that practitioners learn about new therapeutic options. Healthcare providers should continue to learn how to optimize their patients' skin, mental health, and quality-of-life outcomes.
Attention to Patient Perceptions
In addition to physical effects, acne profoundly affects patients' quality of life.38 Healthcare providers should be mindful of patients' emotional well being and also consider patients' goals and expectations. This comprehensive approach is crucial to the identification of an individualized and more successful treatment strategy.38
Clascoterone: Evaluating Clinical Success
Clascoterone 1% topical cream is an androgen receptor inhibitor designed for topical use. Although the exact mechanism of clascoterone for the treatment of acne is not known, preclinical evidence indicates clascoterone binds to and blocks the androgen receptor to decrease androgen-driven sebum production, making it the first approved topical anti-androgen acne therapy (Figure 1).39 In vitro studies have shown that clascoterone competes with DHT for binding to the androgen receptor, reducing production of inflammatory cytokines and sebum components with efficacy comparable to that of spironolactone within the same donor.39,40 Notably, clascoterone is rapidly metabolized in the skin into cortexolone, an endogenous bioproduct, which has no androgen activity and only weak glucocorticoid activity.39,41 In the Phase 2 trials of clascoterone, cortexolone plasma levels were generally below or near the lower limit of quantitation, confirming a localized effect of clascoterone at the site of topical application with consequent minimal systemic anti-androgenic effects.42 The Phase 3 clinical trials for clascoterone further demonstrated efficacy and safety in moderate to severe facial acne in both male and female patients through week 12.43 In the 2 identical studies, clascoterone significantly reduced both inflammatory lesion counts and noninflammatory lesion counts as well as Investigator's Global Assessment score.43 Moreover, the tolerability and safety profile of clascoterone was consistent with those of vehicle cream in both male and female patients, supporting the therapeutic value of clascoterone as a new treatment option for acne in potentially more diverse patient populations.43 Evidence from the subsequent 9-month extension study (CB-03-01/27) enrolling clascoterone- and vehicle-treated patients from the two Phase 3 trials confirmed the potential of clascoterone for long-term use and suggested that this topical androgen receptor inhibitor could also be used safely to treat truncal acne.44 The significant systemic effects seen with oral anti-androgen agents, including reduced libido and feminization
