Exploring daily practice performance of dupilumab in atopic dermatitis: Moving towards personalized treatment

Dupilumab is the first biologic approved for the treatment of patients with moderate-to-severe atopic dermatitis (AD) and proved high efficacy and safety in large randomized controlled trials. However, we know that the highly regulated situations in these trials can lead to a difference in treatment effect compared to the reality in daily practice. Given the heterogeneous nature of AD, it is unlikely that every patient will respond the same to a particular treatment. In contrast to the current “one-size-fits-all” approach, there will be a great need for more patient-centered treatment strategies. The studies described in this thesis aimed to assess the performance of dupilumab in daily practice and to optimize dupilumab treatment for the individual patient. As shown in Chapter 2, treatment with dupilumab in daily practice resulted in a rapid improvement in clinical outcomes combined with a favorable safety profile. Conjunctivitis was more frequently reported as a side effect compared to the clinical trials. As shown by a patient-reported outcome, the majority of patients was satisfied with dupilumab treatment (Chapter 3). Looking from a different angle with a more holistic approach, by using drug survival, dupilumab had an overall good drug survival persistent up to three years (Chapter 4 and 5), meaning that only few patients discontinued dupilumab treatment due to ineffectiveness and/or side effects. Various variables were found to predict discontinuation of dupilumab treatment ineffectiveness and/or side effects. Personalized treatment with dupilumab in AD could also benefit from predictive models. However, as shown in the performed prediction studies (Chapter 5, 7 and 9) developing a prediction model was challenging. A following question was whether it was possible to reduce the dose of dupilumab while maintaining clinical effectiveness. In Chapter 6, a broad range and relatively high serum dupilumab levels were found after 16 weeks of treatment in AD patients, with no relation to treatment response and side effects during the first year of treatment. Therefore, it might be possible that some patients can maintain clinical effectiveness with lower serum dupilumab levels by prolonging dupilumab interval. This was confirmed by our results described in Chapter 8. In Chapter 9, we concluded that our disease activity guided dosing regimen was successful in 83.3% of the patients while maintaining controlled disease. Although a significant effect after start tapering was observed for EASI and NRS pruritus, these scores remained low and still fulfilled the criteria of mild disease. In total, 401 patients had a dupilumab dose reduction with a total estimated cost saving of 3,977,033.98 EUR. In Chapter 10 and 11 we found a positive effect of dupilumab on the atopic comorbidities food allergy and asthma in AD patients. Hence, introduction of dupilumab has led to a major positive shift in the treatment paradigm of AD, and has significantly improved the quality of life for many AD patients. It will be exciting to see what the future holds for the treatment of AD with subsequent introduction of new advanced targeted therapies