Less can be more: The case for extended dosing intervals in biologic therapy for AD

Abstract

Atopic dermatitis (AD) is a chronic, debilitating and intensely pruritic eczematous disease. Until recently, treatment options were largely limited to topical corticosteroids and topical calcineurin inhibitors. In cases of severe and refractory disease, systemic immunosuppressants such as cyclosporine A—the only licensed systemic drug for AD—methotrexate, azathioprine, mycophenolate and short-term oral glucocorticoids were used.¹

The introduction of biologics targeting the interleukin (IL)-4/IL-13 pathway has revolutionized AD treatment. Dupilumab, which inhibits the IL-4 receptor-α (also part of the IL-13 receptor complex), as well as Tralokinumab and Lebrikizumab, both anti-IL-13 antibodies, have significantly expanded the therapeutic armamentarium and improved treatment efficacy.² Phases 2 and 3 clinical trials for these biologics evaluated various dosing regimens, leading to their current approval with fixed biweekly dosing intervals following an initial loading dose—Dupilumab and Tralokinumab are administered every 2 weeks, whereas Lebrikizumab transitions from biweekly dosing to a 4-week interval after 24 weeks of treatment.³

However, these trials also included patients randomized to alternative dosing schedules, some of whom achieved comparable treatment success, as measured by EASI-75 (Eczema Area and Severity Index) and Investigator's Global Assessment (IGA) scores of 0 or 1.³ Additionally, emerging real-world evidence suggests that certain patients may maintain disease control with extended dosing intervals, potentially optimizing treatment burden and cost-effectiveness.

The transition from classical immunomodulators to biologics has been previously described. However, individualized dosing of biologics for AD patients has received little attention until now.⁴ The guiding principle for medication use in treating any disease or patient should be to prescribe as much as necessary but as little as possible. This approach minimizes side effects and patient discomfort while keeping treatment costs low, all while ensuring therapeutic goals are met.

In their paper, Jacobson et al.⁵ review the literature on dosing intervals for biologics in atopic dermatitis, specifically exploring the potential for extending these intervals. Using data from the LIBERTY-AD SOLO studies (Dupilumab), ECZTRA 1 and 2 (Tralokinumab), ADVOCATE 1 and 2 (Lebrikizumab) and real-world evidence, they assess both the feasibility of prolonged dosing and the patient profiles most suitable for this approach.

Their analysis suggests that dosing intervals can be extended in up to half of patients undergoing biologic therapy. Moreover, if treatment efficacy declines, reverting to the original dosing schedule typically restores disease control. These findings could significantly impact our daily treatment strategies for atopic dermatitis.

CV has received honoraria, served on add boards and/or received funding from Abbvie, Almirall, Sanofi, Leo Pharma, Pfizer and Pierre Fabre.