Clinical and translational research by Daphne Bakker and colleagues at UMC Utrecht has provided new leads for improved patient profiling and a better prediction of response to treatment with dupilumab, a biologic immune-modulating drug for the treatment of moderate-to-severe atopic dermatitis. On September 28, 2021 Daphne Bakker received her PhD cum laude at Utrecht University.

Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases worldwide. Due to new targeted treatments that are being developed, treatment of AD is moving towards an era of more personalized medicine. The big challenges with these new treatments are to predict the most optimal treatment for the individual patient, and to monitor and prevent side effects. The Dutch Federation of University Medical Centers (NFU) has designated the Department of Dermatology & Allergology at UMC Utrecht as a national center of expertise for patients with difficult to treat AD. As a result, the center is heavily involved in clinical and translational research on atopic dermatitis and patients from all over the Netherlands are referred to UMC Utrecht because of its specific expertise.

Biomarker signature

In her thesis, Daphne Bakker (Department of Dermatology & Allergology and Center for Translational Immunology, UMC Utrecht) and colleagues describe translational research that has resulted in the construction of a predictive biomarker signature model (using a panel of 10 serum biomarkers), which is able to identify a subgroup of difficult-to-treat AD patients in need of systemic treatment. Next, they found that four subtypes of AD patients can be identified (in both adult and pediatric patients) based on serum biomarker profiles, which is helpful to select the optimal treatment.

Long-term effects of treatment

Her research also focused on clarification of early and long-term immunological effects of the monoclonal antibody dupilumab, the first biologic treatment for AD, and the mechanism underlying the side effect profile related to treatment with this biologic. Daphne Bakker confirmed a rapid mechanism of action of dupilumab, already within two hours after the first administration, which was accompanied by a strong immunological effect after 4 weeks of treatment. During a 12-month follow-up of 167 dupilumab-treated AD patients, it appeared that 20 percent developed moderate-to-severe conjunctivitis (confirmed by an ophthalmologist) within 2 months of treatment. This resulted in dupilumab dose adjustments in 30 percent and discontinuation of dupilumab in 9 percent of these patients.

Targeted treatment strategies

Daphne Bakker, reflecting on the outcomes of her research: “The treatment of AD is rapidly shifting towards more personalized healthcare. Our findings have confirmed that AD is an extremely heterogeneous disease. By describing the biomarker profiles that distinguish the different patient clusters, we showed that for subgroups of patients, specific inflammatory pathways might play an important role in the development of AD. Therefore, new immune therapies are underway that target these pathways. The biomarker signatures, the algorithm that we developed, together with specific comorbidities and risk factors for side effects of treatment, may contribute to further targeted treatment strategies.”

Nearly 400,000 patients

Atopic dermatitis is one of the most common chronic inflammatory skin diseases worldwide, with a prevalence of up to 15 percent in children and up to 10 percent in adults. AD is characterized by itchy, red, swollen and ‘cracked’ skin, resulting in persistent pruritus, pain, sleep disturbances and symptoms of anxiety and depression. This may lead to a profound impairment of quality of life. AD usually starts early in life and often disappears after puberty. It is a disease for which there is an innate 'predisposition' and which is associated with asthma and hay fever. According to the RIVM, nearly 400,000 people in the Netherlands have AD with a health care cost of €150 million per year.

PhD defense

Daphne Bakker, MD (1992, Alphen aan den Rijn) defended her PhD thesis cum laude on September 28, 2021 at Utrecht University. The title of her thesis is “Patient profiling and prediction of response to immune-modulating treatment in moderate-to-severe atopic dermatitis”. Supervisors were dr. Marjolein de Bruin-Weller (Department of Dermatology & Allergology) and prof. dr. Femke van Wijk (Center for Translational Immunology). Co-supervisors were dr. Judith Thijs (Department of Dermatology & Allergology) and dr. Julia Drylewicz (Center for Translational Immunology). In 2021, Daphne Bakker has started her training at UMC Utrecht to become a dermatologist.