Discovering Dermatology Times: August 2024 Print

The August issue of Dermatology Times includes a collection of thought-provoking articles and topics ranging from the use of OX40 inhibitors for atopic dermatitis to neoadjuvant and adjuvant vismodegib for complex basal cell carcinomas. Be sure to read the highlights from the issue below. Also, don’t miss a moment of Dermatology Times by signing up for our eNewsletters and subscribing to receive the free print issue and supplement each month.

Is OX40 Inhibition the Next Game Changer for Atopic Dermatitis?

Within the past 5 years, it has been exciting to see new treatments cater to targeting fundamental pathways in atopic dermatitis (AD). In 2017, dupilumab (Dupixent; Sanofi) significantly changed clinical practice as the first FDA-approved treatment for AD. Following its release, several other systemic agents have been introduced to market.

As of this article, additional FDA-approved therapies for AD include IL-13 inhibitor tralokinumab (Adbry; LEO Pharma), Janus kinase (JAK) 1 inhibitor upadacitinib (Rinvoq; AbbVie), and JAK1 inhibitor abrocitinib (Cibinqo; Pfizer Inc). Those currently in phase 3 studies include IL-13 inhibitor lebrikizumab (Ebglyss; Eli Lilly and Company) and IL-31 inhibitor nemolizumab (Galderma). Pharmaceutical companies have realized there is an unmet need for additional therapeutic options beyond our current landscape.

Ultimately, we ask ourselves: If one medication does not work or does not work fully, then what is next?

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Crystal Structure of Bimekizumab Fab Fragment Supports Efficacy of IL-17 Dual Inhibition

In a recent scientific paper published in the Journal of Investigative Dermatology, Adams et al sought to better understand how bimekizumab (Bimzelx; UCB) binds to interleukin (IL)-17F and how bimekizumab’s unique mechanism of action can benefit patients with psoriasis and psoriatic arthritis. In Adams et al’s research, the technique of X-ray crystallography was used: crystals of bimekizumab fragment antigen-binding (Fab) in complex with IL-17F (BKZ –IL-17F) were generated using hanging drop vapor diffusion, an X-ray diffraction dataset was collected, and the crystal structure was determined by molecular replacement using coordinates of an in-house Fab and IL-17F.

"It was a privilege to be a part of this investigation elucidating the structural mechanism of bimekizumab inhibition of IL-17A/F. The main takeaway for practicing dermatologists is that bona fide molecular science backs up and explains the potent clinical efficacy observed in patients when using this biologic," said Christopher Bunick, MD, PhD, study author, associate professor of dermatology and translational biomedicine at Yale University School of Medicine in New Haven, Connecticut, and Dermatology Times’ 2024 Winter Editor in Chief.

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Navigating the Challenges of Melasma Treatment and Achieving Trial Equity in Melanin-Rich Skin

Melasma, complex and often persistent in nature, poses significant diagnostic and treatment challenges, particularly for patients with darker skin types.

This hyperpigmentation presents differently depending on the individual’s skin tone, typically causing dark brown patches in individuals with lighter skin types, or gray-brown patches in patients with skin of color. Its pathogenesis, an overproduction of pigmentation by melanocytes in the skin, is a process more pronounced in individuals with darker skin tones due to higher melanocyte density.

It is crucial to navigate these complexities to provide effective care while managing patient expectations. This article explores the primary challenges, recent advances, and future directions in melasma research and treatment, with insights from Tracee Blackburn, PA-C, a board-certified physician assistant serving residents of Chicago, Illinois, at Medical Dermatology Associates of Chicago.

For patients with melanin-rich skin, uneven skin tone is a common concern, often leading to consultations for hyperpigmentation. Differentiating melasma from other hyperpigmentation causes is challenging due to overlapping clinical features.

“Patients want to know the what, when, how, and why,” Blackburn said. “One of the primary challenges in treatment is informing the patient that melasma itself is challenging to treat. It is a multifactorial condition stemming from genetics, hormonal changes, UV exposure, and more.”

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Neoadjuvant and Adjuvant Vismodegib for Complex Basal Cell Carcinomas

Basal cell carcinoma is a slow-growing tumor that rarely metastasizes; however, a few patients have recently presented to our hospital with rare, large basal cell carcinomas infiltrating both the skull and brain. Despite basal cell carcinoma being the most common nonmelanoma skin cancer in the United States, it is uncommon for a basal cell carcinoma to become so advanced that it penetrates the skull. These patients in their 60s and 70s had limited access to the hospital health care system, and some of them had to focus on caring for their loved ones rather than their own health care needs. When presented with these patients with large basal cell carcinomas, the options are limited for treatment.

Vismodegib (Erivedge; Genentech) received approval from the FDA in 2012 and has been effectively used for patients with metastatic or locally advanced basal cell carcinomas who are not eligible candidates for radiation or surgery.1 It is also approved for patients with locally advanced basal cell carcinoma that has recurred following surgery. Vismodegib is a hedgehog pathway inhibitor that binds to the smoothened protein, preventing the creation and growth of a basal cell carcinoma tumor. Although surgery is the gold standard for treatment and reducing recurrence, sometimes initially starting with surgery would lead to a higher morbidity and mortality rate. In some cases, to prevent metastases of basal cell carcinoma, vismodegib has been used as a maintenance therapy after surgery. To improve overall outcomes for patients with large basal cell carcinomas, it has been beneficial to employ the use of vismodegib as a neoadjuvant and/or adjuvant treatment.

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