Lebrikizumab plus TCS safely improves patients with moderate-to-severe atopic dermatitis
Lebrikizumab, an interleukin (IL)-13 monoclonal antibody, taken every 4 weeks and in combination with topical corticosteroid (TCS) is safe and effective in patients with moderate-to-severe atopic dermatitis (AD), results from a phase II study have shown.
“The results of this proof-of-concept study suggest that IL-13–mediated signalling pathways play an important role in the pathogenesis of AD, and the blockade of this cytokine could lead to significant clinical benefit,” researchers said. [J Am Acad Dermatol 2018;78:863-871.e11]
A total of 209 patients received lebrikizumab. Significantly more patients in the lebrikizumab (125 mg every 4 weeks) group than those in the placebo group (82.4 percent vs 62.3 percent; p=0.026) had achieved Eczema Area and Severity Index (EASI)-50 at week 12. No statistically significant improvement in EASI-50 was seen in patients receiving a single dose of lebrikizumab compared with placebo.
Adverse events were mostly mild or moderate and were comparable between treatment groups (66.7 percent with all lebrikizumab doses vs 66.0 percent with placebo).
“Patients with moderate-to-severe AD showed improvements with lebrikizumab treatment, even with single doses and twice daily TCS use,” researchers said. “However, the twice-daily use of TCS before and during this trial in all study groups impaired the ability to fully assess the efficacy of lebrikizumab in AD, and monotherapy studies may be needed to assess the efficacy of lebrikizumab.”
For this study, researchers based their dosing from the lebrikizumab asthma programme and the objective of characterizing both dose-response relationships and dosing frequency requirements in AD.
There were dose-response relationships seen across multiple endpoints, and the trends toward improved efficacy with increasing dose and duration suggested that further increases in the dose or treatment duration could improve efficacy, they added.
Furthermore, the safety profile of the study drug was consistent with that in the extensive asthma programme. [N Engl J Med 2011;365:1088-1098; Thorax 2015;70:748-756; Clin Exp Allergy 2014;44:38-46; J Allergy Clin Immunol 2013;132:567-574.e12; Lancet Respir Med 2016;4:781-796]
Previously reported increases in peripheral blood eosinophil counts with lebrikizumab treatment are possible due to decreased eosinophil trafficking from the blood to the airways as a result of reduced chemotaxis by blocking IL-13 activity. [N Engl J Med 2011;365:1088-1098; Lancet Respir Med 2016;4:781-796]
In this phase II study, adults with moderate-to-severe AD were required to use TCS twice daily and then randomly assigned to lebrikizumab 125 mg single dose, lebrikizumab 250 mg single dose, lebrikizumab 125 mg every 4 weeks for 12 weeks, or placebo every 4 weeks for 12 weeks, after a 2-week TCS run-in. The percentage of patients achieving EASI-50 at week 12 was the primary endpoint.
Certain limitations are present in this study. “Protocol-mandated twice daily TCS treatment limits our understanding of the efficacy of lebrikizumab as a monotherapy,” researchers said. “The short study duration did not enable long-term efficacy or safety evaluations.”