Understanding the Medical Dictionary for Regulatory Activities (MedDRA) reporting of herpes simplex virus (HSV) adverse events in atopic dermatitis clinical trials.

Drug efficacy is best evaluated by randomized, controlled, double-blind clinical trials; however, safety is harder to assess. The Medical Dictionary for Regulatory Activities (MedDRA) is used to track and categorize adverse events (AE) during clinical trials. Recent atopic dermatitis (AD) clinical trials were reviewed to illustrate how an understanding of MedDRA may be helpful when evaluating the rates and nature of adverse events related to herpes simplex virus (HSV) infection. All completed AD clinical trials (excluding phase I studies) with results on clinicaltrials.gov (01/01/2018-01/31/2023) were queried in January 2023. MedDRA version, preferred term (PT) for AEs captured as "HSV", PTs for other AEs possibly related to HSV, frequency thresholds for reporting non-serious AEs, and route of treatment were recorded. Of the 46 clinical trials, 17 had PTs for AEs captured as "HSV". Among all studies, 11 different versions of MedDRA were utilized, from versions 10 to 24.1. In all studies, PTs for AEs captured as "HSV" were listed in the Infections and Infestations system organ class (SOC) classification of MedDRA. PTs varied from "herpes simplex", "herpes virus infection", "herpes ophthalmic", "ophthalmic herpes simplex", "nasal herpes", "oral herpes", "herpes dermatitis", "eczema herpeticum", "genital herpes simplex", and "genital herpes." While one clinical trial of dupilumab (NCT03359356) simply reported the PT "oral herpes" as an AE, a clinical trial of DS107 (NCT03817190) reported the PTs "oral herpes", "herpes simplex", and "herpes virus infection" separately. In the DS107 clinical trial, it is unclear if the same adverse event was reported under multiple PTs or if multiple HSV-related AEs occurred. Although the definition of HSV is unchanged from 2018 to 2023 and there are few changes between MedDRA versions, coding for HSV is complex. HSV events can be reported in different ways, which may impact the interpretation of a drug's safety profile.

Management of Pediatric Psoriasis: A U.S. Survey Based on Visits from the National Ambulatory Medical Care Survey (NAMCS).

INTRODUCTION: Approximately one-third of psoriasis cases present in the first two decades of life. Many psoriasis treatments are approved by the U.S. Food and Drug Administration (FDA) for adults, including topical agents, systemic non-biologic agents, and systemic biologic agents. Only a handful of psoriasis treatments are FDA approved for children. Given the constantly evolving landscape of pediatric psoriasis management, our aim is to characterize how children with psoriasis are treated in the U.S. METHODS: Data from the 2003-2016 and 2018 National Ambulatory Medical Care Survey (NAMCS) were used to evaluate patient demographics and treatment patterns for visits of children with psoriasis. Visits were stratified by those with a diagnosis of psoriasis and those for children with a diagnosis of psoriasis. Separate analyses for visits of children with a diagnosis of psoriasis were performed, including for sex, race, ethnicity, age, specialty of provider seen, and medications prescribed. RESULTS: Pediatric psoriasis visits accounted for 3.3% of visits with psoriasis from 2003 to 2016 and in 2018; about one-third of those visits were to primary care providers. Children with psoriasis were prescribed a variety of topical and systemic medications, of which the most frequently prescribed treatments were topical tacrolimus, followed by topical clobetasol and topical betamethasone dipropionate or betamethasone valerate. Etanercept was the only biologic prescribed to children. At least 59% of the visits for children with a diagnosis of psoriasis included a topical prescription while at least 5.3% of the visits included a systemic prescription. CONCLUSION: Use of off-label treatments was common for pediatric psoriasis. Most children with psoriasis were treated with topicals, of which tacrolimus, an unapproved treatment, was the most common. The frequent use of tacrolimus could indicate an avoidance of corticosteroids in children.

Oral Tetracycline-Class Drugs in Dermatology: Impact of Food Intake on Absorption and Efficacy.

Tetracycline-class drugs are frequently used in dermatology for their anti-inflammatory properties to treat skin diseases such as acne, rosacea, and hidradenitis suppurativa (HS). The American Academy of Dermatology (AAD) clinical guidelines do not offer guidance regarding the co-administration of food with tetracycline-class drugs. The objectives of this study were to review the available evidence regarding whether taking tetracycline-class drugs with food decreases systemic absorption and is associated with an impact on clinical efficacy. A literature search was conducted using the PubMed database between February to May 2023 using the keywords "tetracycline-class drugs", "pharmacokinetics", "absorption", and "dermatology". Inclusion criteria included articles written in English and relevant to the absorption and efficacy of tetracycline-class drugs. This search yielded 131 articles written between 1977 to 2022, of which 29 met the criteria for review. United States Food and Drug Administration (FDA)-approved prescribing information for oral formulations of tetracycline, doxycycline, minocycline, and sarecycline were reviewed. Systemic absorption of tetracycline decreased when co-administered with food. Systemic absorption of oral doxycycline and minocycline was variable with food co-administration. The impact on bioavailability varied with the drug formulation and dosage. The absorption of oral sarecycline decreased when administered with food. Sarecycline is the only oral antibiotic where population pharmacokinetic studies demonstrated limited or no impact of food intake on clinical efficacy. There are no available data for other tetracycline-class drugs in dermatology. If patients find it more tolerable to take doxycycline, minocycline, and sarecycline with food to avoid gastrointestinal distress, this may merit consideration to encourage patient adherence. Since the impact of food intake on absorption varied with the dosage form of doxycycline and minocycline, consulting the appropriate package insert may give clinicians additional insight into differences in the various formulations.