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Practical Dermatology® takes a closer look at fascinating reports from the recent Acne and Rosacea (ARM) Meeting and the Revolutionizing Atopic Dermatitis (RAD) Meeting, both occurring in late 2023. The reports cover a range of important studies and expert perspective for practitioners treating patients with acne, rosacea, and atopic dermatitis (AD).

ARM Conference: Navigating Antibiotic Use for Acne and Rosacea

Growing apprehensions surrounding antibiotic resistance in acne and rosacea treatments, coupled with their linked adverse effects, have prompted a closer examination of their use. Emmy Graber, MD, MBA, recently delivered comprehensive insights and considerations regarding these concerns, emphasizing the significance of adhering to guidelines and exploring alternative approaches. Her discourse, a focal point at the virtual Acne and Rosacea (ARM) Meeting, underscored the pivotal role of responsible antibiotic stewardship for achieving effective treatment outcomes.

Dermatologists in particular have been highlighted for prescribing a higher number of oral antibiotic courses than any other specialty. This pattern, she said, raises red flags regarding the potential risks these medications pose to patients, urging a reevaluation of their usage protocols.

Adherence, Acne, and Antibiotics

In adherence to the American Academy of Dermatology’s (AAD) 2016 consensus guidelines, oral antibiotics are recommended as a primary treatment for patients with moderate-to severe acne. However, they are suggested to be utilized in conjunction with topical retinoids and benzoyl peroxide products, aiming to shorten the duration of antibiotic use and avoid the development of resistance.

The ideal duration of oral antibiotic therapy remains a point of contention within the dermatological community, as highlighted by Dr. Garber, founder of the Dermatology Institute of Boston and an Affiliate Clinical Instructor at Northeastern University. There are currently no definitive guidelines regarding the abrupt cessation or gradual reduction of these medications, nor is there consensus on retreatment for acne flares post-initial antibiotic courses, she noted.

Antibiotic stewardship, emphasized by the Center for Disease Control and Prevention due to growing concerns about antimicrobial resistance, underlines the importance of appropriate antibiotic use. This initiative advocates for precise dosing, timing, duration, and a preference for narrow-spectrum antibiotics when feasible.

The Tetracycline Family

Dr. Graber underscored the prevalence of tetracycline family antibiotics in dermatological practice. This class, encompassing tetracycline, doxycycline, minocycline, and sarecycline, stands as the most commonly prescribed and extensively studied oral antibiotics for acne treatment. Each member displays efficacy, albeit with varying side-effect profiles.

Doxycycline, for example, possesses both antimicrobial and anti-inflammatory properties at different dosage ranges. However, concerns regarding gastrointestinal side effects prompt recommendations for its consumption with food and water. Additionally, the dose-dependent nature of phototoxicity raises queries about its clinical significance in acne management.

The use of subantimicrobial dosing of doxycycline (40 mg) for rosacea showcases predominantly anti-inflammatory effects, reducing the risk of bacterial resistance and gastrointestinal distress. This modified release formulation is the only FDA-approved oral agent specifically for inflammatory lesions of rosacea.

Minocycline, characterized by increased vestibular side effects and potential skin complications like hyperpigmentation, offers both oral and topical formulations for rosacea and acne treatment, but with varying incidence rates of adverse events. “If one chooses to use minocycline to treat rosacea, there are several strategies to lessen the likelihood of side effects developing. Many of the side effects such as cutaneous hyperpigmentation and drug-induced lupus, are more common with long term use such as use greater than one year. Therefore, shortening the duration of use may help to reduce these types of minocycline specific risks. Reducing the likelihood of vestibular side effects can be accomplished by using weight-based dosing or extended-release formulations,” noted Dr. Graber.

Concerns about antibiotic resistance rates, especially noting the reported 57% antibiotic-resistant Cutibacterium acnes (C. acnes) isolated from acne patients treated with doxycycline, prompt exploration of strategies to mitigate resistance, she said; Dr. Garber suggests multiple strategies for countering these rates. “There are several strategies that one can utilize in order to mitigate resistance rates. Firstly, one could consider using a narrow spectrum rather than a broad-spectrum antibiotic which will give a more targeted approach to reducing Cutibacterium acnes and lessen the likelihood of resistance. Secondly, one could choose to use sub-antimicrobial dosing of an antibiotic which is typically done with doxycycline as it has the highest degree of anti-inflammatory effect of the tetracycline class of antibiotics.” She continued, “At doses less than 50 milligrams a day, there is much more of an anti-inflammatory effect than there is of an antibacterial fact thus lessening the chance for resistance. Thirdly, concomitantly using topical benzoyl peroxide along with a topical or oral antibiotic will lessen the likelihood of the development of antibiotic resistance by cutaneous bacteria,” advised Dr. Garber.

Sarecycline, an FDA-approved narrow-spectrum tetracycline antibiotic, stands out as a novel option for treating inflammatory acne. It boasts efficacy data even in younger patients, with notably lower reported rates of gastrointestinal and phototoxic side effects.

Antibiotics and Oral Contraceptives

Another crucial aspect highlighted by Dr. Graber is the interaction between antibiotics and oral contraceptives. While certain anti-infectives can compromise the effectiveness of combined oral contraceptives, the tetracycline class hasn’t demonstrated such effects significantly.

When considering the effectiveness of oral antibiotics versus oral contraceptives in treating acne, Dr. Graber highlights research findings.

“Studies indicate that while oral antibiotics are more effective at improving acne in the short term—within three months or less—oral contraceptives demonstrate comparable efficacy to oral antibiotics after six months. Therefore, for patients who are willing to wait six months for their acne to improve, an oral contraceptive may be a better choice than oral antibiotics. However, for those who desire a faster improvement, oral antibiotics may give more improvement in the shorter term. In my practice, I will often combine these agents and start female patients on both an oral contraceptive and an oral antibiotic with the goal of stopping the oral antibiotic in the coming months and then continuing the oral contraceptive for long-term maintenance treatment,” elaborated Dr. Graber.

Selecting an appropriate oral antibiotic for dermatological conditions necessitates a careful consideration of efficacy, duration, combination therapy, resistance issues, and the varied side-effect profiles among the tetracycline family members. Such considerations are vital in optimizing treatment outcomes while minimizing risks associated with antibiotic use in dermatology. —by Dibash Das, PhD

RAD Conference: Treatment Gaps Linked to Insufficient Disease Control in Moderate-to-Severe AD

A recent study presented at the Revolutionizing Atopic Dermatitis (RAD) Virtual Conference highlighted has shed light on the persistent issue of therapeutic inertia in the treatment of moderate-to-severe atopic dermatitis (AD), even with the advent of newer, advanced systemic therapies. Over a 12-month period, many patients treated with systemic therapies failed to achieve satisfactory control of their condition.

Lead author Lawrence Eichenfield, MD, chief of pediatric and adolescent dermatology at Rady Children’s Hospital-San Diego and a professor of dermatology and pediatrics and vice-chair of the department of dermatology at UC San Diego School of Medicine, as well as a member of the Practical Dermatology® Editorial Board, addressed this concern by emphasizing the need for a dynamic and goal-oriented approach to tackle therapeutic inertia and enhance treatment efficacy.

“Therapeutic inertia is the delay or failure of timely adjustment to therapy when treatment goals are not met,” Dr. Eichenfield told Practical Dermatology. “But treatment goals aren’t ‘set in stone,’ and are influenced by the efficacy of alternative medications, as well as the perception of risks associated with the medications individuals are on and other agents they may consider as alternatives.”

Measuring Therapeutic Inertia

The current study aimed to evaluate the occurrence of therapeutic inertia, focusing on patients whose condition did not respond adequately to the initial systemic therapy, be it Advanced Systemic Therapy (AST) like upadacitinib or dupilumab, or Conventional Systemic Therapy (CST) like methotrexate or systemic corticosteroids. Consequently, the researchers conducted a longitudinal analysis of 3,457 patients from 39 centers in the US and Canada diagnosed with moderate to severe AD. To be eligible, patients had to have a validated Investigator’s Global Assessment of AD (vIGA-AD) score of 3 or 4 within 45 days before starting the systemic treatment or within 14 days after the treatment began.

Dr. Eichenfield said that the study was based on establishing optimal response (defined as a vIGA-AD score ≤1 (clear or almost clear skin), BSA ≤ 2%, and WP-NRS itch score of 0/1 (complete or almost complete skin resolution), versus inadequate response and delayed or failure to escalate treatment in patients not achieving adequate disease control (defined as “therapeutic inertia”). Patients who had previously undergone either advanced or conventional systemic therapy for AD before the set index date were excluded from the study.

Among the 2,107 patients diagnosed with moderate to severe AD, 445 met the study criteria. These patients were predominantly adults (63.8%), female (62.0%), and identified as Non-Hispanic White (45.4%), with an average age of 31 years. The majority (92%) commenced treatment with AST, with dupilumab being the most frequently used systemic therapy (86.5%). The mean vIGA-AD score at the beginning of AST treatment was 3.3, while for CST, it was 3.6 (P<0.01). The average baseline itch score was 7.6.

During the follow-up period, the most commonly used AST for patients with atopic dermatitis was dupilumab. Out of 395 AST patients, 36.7% also utilized concurrent topical corticosteroids or topical calcineurin inhibitors. Despite receiving either AST or CST for up to 12 months, a notable proportion of patients faced challenges with their treatment responses.

Benefits May Not Be “Significant Enough”

Regarding inadequate responses in achieving moderate targets, at the 6-month mark, approximately 37% and nearly 67% of AST-treated patients experienced insufficient skin clearance and itch relief, respectively. By the 12-month milestone, these figures improved to around 30% and 66%, respectively. Similar patterns were observed among CST-treated patients.

In terms of not achieving optimal targets, 82% and 79% of AST-treated patients did not reach satisfactory skin clearance and itch relief, respectively, at 6 months. These percentages slightly increased to approximately 85% and 88%, respectively, by the end of 12 months. Comparable trends were seen in CST-treated patients.

“This suggests that adding topical calcineurin inhibitors or corticosteroids may not provide what I would call ‘significant enough’ benefits and may contribute to therapeutic inertia,” Dr. Eichenfield noted.

The Importance of Defining Treatment Objectives

Additionally, the study highlighted that patients starting AST treatment after September 21, 2021, when new AST options (tralokinumab, upadacitinib, and abrocitinib) were introduced, had similar rates of inadequate responses over the 12-month period compared to the overall AST cohort.

“Currently, a post hoc analysis is underway to delve deeper into how baseline characteristics affect treatment outcomes,” added Dr. Eichenfield. “This analysis aims to provide a clearer understanding of the impact of these characteristics on therapeutic inertia and persistent inadequate response to treatment.”

Dr. Eichenfield also further highlighted the importance of redefining treatment objectives.

“Aiming for higher measures of efficacy is important. Regular, thorough assessments and documentation of outcomes (such as itch response and skin clearance) are important to evaluate progress against these goals. When these objectives are not met within a specified timeframe (3-6 months) indicating inadequate response, clinicians should be prepared to adjust the treatment strategy. This might include switching to more potent or novel therapeutic options that align better with the patient’s condition.”

In addition to medical adjustments, Dr. Eichenfield stressed the significance of patient education and engagement throughout the treatment journey.

“Emphasizing patient education and engagement in this process is vital to ensure understanding, encourage appropriate shared decision making, and promote adherence to the treatment regimen,” he said. “Such an approach not only addresses the physical symptoms of atopic dermatitis but also considers the psychological and quality-of-life impacts, thereby fostering a more holistic and effective management of the disease.” —by Dibash Das, PhD

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