Emerging drugs for the treatment of atopic dermatitis: a focus on phase 2 and phase 3 trials.

INTRODUCTION: Atopic dermatitis (AD) is an inflammatory skin condition that affects millions of pediatric and adult patients with well-studied impact on morbidity and quality of life. Management occurs in a stepwise fashion beginning with preventative measures before immunomodulators are introduced. However, challenges remain in treatment of moderate-to-severe atopic dermatitis that is refractory to first- and second-line treatments and there are only few topical anti-inflammatory options, especially for pediatric patients. AREAS COVERED: New medications are required to address these gaps as lesions may persist despite treatment or patients may discontinue treatment due to actual or anticipated adverse effects of mainstay medications. Emerging research into the pathophysiology of AD and the immune system at large has provided opportunities for novel interventions aimed at stopping AD mechanisms at new checkpoints. Clinical trials for 36 agents currently in phase 2 or phase 3 are evaluated with particular focus on the studies for, B244, CBP-201, tapinarof, lebrikizumab, nemolizumab, amlitelimab, and rocatinlimab as they explore novel pathways and have some of the most promising results. EXPERT OPINION: These clinical trials contribute to the evolution of AD treatment toward greater precision based on salient pathways with a particular focus on moderate-to-severe AD to enhance efficacy and minimize adverse effects.

Longitudinal Risk Management for Patients with Increased Risk for Breast Cancer.

INTRODUCTION: This study aims to characterize longitudinal care management and evaluate the relationship between various patient factors and the likelihood of choosing risk-reducing behaviors in women with increased risk of developing breast cancer. METHODS: A retrospective study was conducted to evaluate all adult female patients who had at least one clinic visit with a surgical provider for discussion of breast cancer risk assessment between January, 2017 to July, 2020 at an academic center. Patients with prior history of breast cancer were excluded. Patient details and strategies pursued at clinic visits were recorded. A time-to-event analysis was performed, and hazard ratios were determined to characterize associations between patient characteristics and time to pursuing risk-reducing care management. RESULTS: There were 283 participants with at least one follow-up visit and 48 (17.0%) ultimately changed their initial strategy to either chemoprevention or prophylactic mastectomy. Patients with gene mutations were 6 times more likely to engage in risk-reducing management compared to those without (hazard ratio (HR) 5.99, P < 0.001). Those with histories of high-risk proliferative changes (HR 7.62, P < 0.001) and hysterectomy (HR 2.99, P = 0.019) were also more likely to engage in risk-reducing management. Age, race, and increased predicted risk of developing breast cancer (estimated by various calculators) were not associated with increased likelihood of engaging in risk-reducing strategies. CONCLUSION: Known gene mutations, history of high-risk proliferative changes, and prior hysterectomy were factors associated with women who were more likely to engage in risk-reducing strategies. These findings, when paired with patient reported outcome measures, may help guide shared decision-making.

Fungal Head and Neck Dermatitis: Current Understanding and Management.

Head and neck dermatitis (HND) is a form of atopic dermatitis (AD) that affects the seborrheic areas of the body and causes greater quality of life detriments than other types of AD. HND can be challenging to treat since first-line topical therapies may be ineffective or intolerable for long-term use on areas affected by HND while dupilumab may cause dupilumab-associated HND (DAHND). Current evidence implicates fungi, particularly Malassezia spp., in the pathogenesis of HND. Penetration of fungal antigens through the defective AD skin barrier activates the innate and adaptive immune systems to cause cutaneous inflammation via the T helper (Th)17 and/or Th2 axes. Malassezia sensitization may distinguish HND from other forms of AD. Multiple double-blind, placebo-controlled trials have shown antifungals to benefit HND, yet the persistence of symptom relief with sustained use remains unclear. Oral antifungals appear more effective than topical antifungals but may be harmful with long-term use. DAHND may also be fungal-mediated given improvement with antifungals and evidence of an overactive immune response against Malassezia in these patients. Janus kinase inhibitors are effective for HND, including DAHND, but may cause significant side effects when administered systemically. OX40/OX40L inhibitors and tralokinumab may be promising options for HND on the horizon. Demographic and environmental factors influence the host mycobiome and should be considered in future precision-medicine approaches as microbiome composition and diversity are linked to severity of HND.