JAK1 inhibitors for the treatment of atopic dermatitis: a focus on pharmacokinetic considerations.

INTRODUCTION: Atopic dermatitis (AD) is associated with reduced quality of life, depression, and anxiety, making efficacious and safe treatments a priority. We will focus on the safety, efficacy, and pharmacokinetics of JAK1 inhibitors used in the treatment of AD. AREAS COVERED: In this review, the pharmacodynamics, pharmacokinetics, safety, and efficacy of JAK1 inhibitors for the treatment of atopic dermatitis are discussed. The data was obtained by searching ClinicalTrials.gov, PubMed, and Google Scholar. Articles between January 2012 and March 2023 were considered for inclusion. EXPERT OPINION: Given the rare, but serious black box warnings with JAK inhibitors, patients and providers may be weary of initiating treatment. In these instances, clinicians may weigh the risks and benefits of treatment with this class. Risk is relative, and while there are risks to treating AD with JAK inhibitors, there are also risks to untreated or undertreated AD, including infection and impairments in mental, physical, and psychosocial function. While JAK1 inhibitors appear to be safe, they were only recently approved for AD in January 2022, and more long-term safety data is needed. We expect to see additional FDA approval of these drugs, new formulations, and more safety and efficacy data in the future.

Do Commonly Used Antimicrobial Topicals Facilitate Venous Leg Ulcer Healing?

OBJECTIVE: To survey which topical antimicrobials are most helpful in treating venous leg ulcers (VLUs). DATA SOURCES: In this narrative review, the authors searched the databases of Google Scholar, Cochrane Library, and Wiley Online Library. STUDY SELECTION: Studies were eligible for inclusion if they studied the effects of antimicrobial agents on chronic VLU healing and were published after 1985. Exceptions to this were in vitro studies of manuka honey and Dakin solution (Century Pharmaceuticals). Search terms included "venous leg ulcer", "nonhealing ulcer", "antimicrobial resistance", and "biofilms". DATA EXTRACTION: Data extracted included design, setting, descriptions of intervention and control groups, outcomes, data collection tools, and potential harms. DATA SYNTHESIS: A total of 19 articles encompassing 26 studies/trials met the inclusion criteria. Of the 26 studies, 17 were randomized controlled trials; the remaining 9 were a mix of lower-quality case series and comparative, nonrandomized, or retrospective studies. CONCLUSION: Studies suggest that VLUs can be treated with multiple different topical antimicrobials. Depending on the extent of chronicity and bacterial colonization, some antimicrobials may be better suited than others.

Avacopan for the Treatment of Anti-Neutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis.

OBJECTIVE: To review the safety and efficacy of avacopan for the treatment of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. DATA SOURCES: A systematic review of the literature was performed using the terms avacopan OR tavneos OR CCX168 OR ANCA-associated vasculitis in PubMed and Google Scholar. Articles between January 2016 and January 2023 were considered for inclusion. Bibliographies and ClinicalTrials.gov were also searched for completion. STUDY SELECTION AND DATA EXTRACTION: Relative English language and human studies related to pharmacology, clinical trials, and safety were included. DATA SYNTHESIS: The 52-week ADVOCATE and 12-week CLEAR clinical trials evaluated the safety and efficacy of avacopan. The remission rate was 65.7% and 54.9% in the avacopan and placebo group, respectively, in the ADVOCATE trial. The Birmingham Vasculitis Activity Score improved by ≥50% in 86.4% of avacopan treated patients and 70% of prednisone treated patients in the CLEAR trial. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE IN COMPARISON WITH EXISTING DRUGS: Glucocorticoids in combination with cyclophosphamide, azathioprine, and/or rituximab have been a mainstay of ANCA-associated vasculitis treatment. However, short- and long-term medication-related adverse effects risk negative outcomes for patients. Avacopan may provide equivalent to better treatment with fewer side effects due to a reduction, if not elimination, of glucocorticoids. CONCLUSIONS: Avacopan used in isolation or combination is safe and effective for ANCA-associated vasculitis.

Ketogenic Diet-induced Prurigo Pigmentosa (the "Keto Rash"): A Case Report and Literature Review.

Prurigo pigmentosa (PP) is a rare inflammatory dermatosis of unknown etiology that primarily affects adolescents and young adults. It is typically characterized by a pruritic eruption of erythematous papules on the trunk and neck that evolves into reticulate hyperpigmentation upon resolution of the inflammatory phase of the rash. It has been associated with various triggers, including the metabolic state of ketosis. Interestingly, the recent increase in popularity of the ketogenic diet for weight loss has led to an increased number of PP cases reported in the literature. We present a case of PP in a 21-year-old Hispanic man, which erupted during strict adherence to a ketogenic diet. We conducted a literature review and identified 19 other cases of PP related to ketogenic diet. While PP has historically been reported primarily in Asia, we found cases occurring in patients of Middle Eastern, Caucasian, Hispanic, Asian, and African descent. On average, the rash presented 31 days after initiating the diet and subsided 18 days after diet cessation. Most cases were treated with an oral tetracycline and resolved with residual hyperpigmentation. We present this information to highlight the increasing association of PP with the ketogenic diet so that early diagnosis and treatment and optimal patient outcomes may be achieved. Dermatologists should be aware of the timing of rash onset and resolution in relation to the diet.