Depth, Speed, and Durability: What Matters Most in Modern Clinical Trials

In a wide-ranging discussion with Dermatology Times, David Cotter, MD, PhD, board-certified dermatologist at Las Vegas Dermatology and current president of the Nevada Society of Dermatology and Dermatologic Surgery, shared clinical perspectives on the evolving role of systemic therapies across inflammatory skin diseases. Drawing from clinical trials, real-world experience, and emerging research tools, Cotter highlighted how treatment selection is becoming increasingly nuanced—and increasingly individualized.

A central theme of the conversation was the use of Janus kinase (JAK) inhibitors in atopic dermatitis (AD). Cotter noted that across network meta-analyses and head-to-head trials, JAK inhibitors as a class have generally demonstrated stronger efficacy than biologics in terms of skin clearance and itch reduction. Trials comparing agents such as upadacitinib and dupilumab illustrate this trend, with JAK inhibitors often showing modest but consistent advantages at the population level. However, Cotter emphasized that averages can obscure clinically meaningful variability. Some patients appear to be “super responders,” experiencing dramatic improvement that exceeds what trial data alone might predict.

To that end, he pointed to emerging molecular tests that may help identify which patients are more likely to respond to JAK inhibitors versus biologics. In practice, Cotter has observed particularly strong responses among patients with more complex or overlapping inflammatory phenotypes, including those with AD complicated by allergic contact dermatitis—an off-label but common clinical scenario.

Safety remains a frequent point of discussion with patients, especially given the boxed warnings associated with JAK inhibitors. Cotter stressed the importance of proactive counseling around risks such as major adverse cardiovascular events, venous thromboembolism, malignancy, and serious infection. At the same time, he noted that long-term safety data from trials and real-world use show these events to be rare and generally consistent with background rates seen in the broader AD population. He cautioned against allowing fear of theoretical risk to overshadow the potential benefits for appropriately selected patients.

Beyond AD, Cotter discussed treatment priorities in psoriasis with comorbid psoriatic arthritis (PsA), underscoring the need for therapies that address joint pain quickly and help prevent long-term structural damage. He also highlighted the value of choosing agents with broader indications when diagnostic uncertainty exists, particularly for axial disease, to ensure patients are adequately covered while awaiting rheumatologic evaluation.

Rare diseases such as generalized pustular psoriasis (GPP) were another focus. Cotter described recent clinical trials as transformative for clinician awareness, emphasizing the acute, potentially life-threatening nature of GPP and the importance of rapid intervention. The availability of an FDA-approved therapy in the United States marks a significant step forward for this historically underserved population.

Finally, Cotter addressed broader issues in dermatology research, including the limitations of subjective endpoints like PASI and EASI scores. He advocated for the development of more objective, quantitative measures — potentially incorporating AI-driven imaging — to reduce variability and improve treatment decision-making.

Taken together, Cotter’s insights reflect a field moving toward greater precision: balancing efficacy, safety, speed of response, and patient-centered outcomes to optimize care across diverse dermatologic conditions.