Clinical Overview: Lebrikizumab for Atopic Dermatitis

Lebrikizumab is a novel monoclonal antibody that binds with high affinity to the IL-13 protein to prevent the interaction between IL-13Rα1 and IL-4Rα, which blocks downstream signal activation along the IL-13 pathway.

Atopic dermatitis (AD) is a long-lasting inflammatory disease of the skin characterized by intense pruritis and recurrent eczematous lesions. Interleukin (IL)-13 is one of the major pathway mediators contributing to AD’s pathophysiology, as it promotes inflammation, epidermal barrier dysfunction, and itching.

Indication

Lebrikizumab is a novel monoclonal antibody that binds with high affinity to the IL-13 protein to prevent the interaction between IL-13Rα1 and IL-4Rα, which blocks downstream signal activation along the IL-13 pathway. Lebrikizumab is being studied in patients 12 to 18 years of age (ADhere) and 18 to 75 years of age (TREBLE) with moderate to severe AD.

Lebrikizumab is a potent inhibitor of the IL-13 signaling pathway, which helps mitigate one of the major contributing factors for AD’s disease progression.

Clinical Trial Data

TREBLE was a randomized, placebo-controlled, double-blinded phase 2 study that enrolled 209 adults 18 to 75 years of age with moderate to severe AD. The researchers randomized participants 1:1:1:1 to receive lebrikizumab 125 mg single dose at baseline, 250 mg single dose at baseline, 125 mg once every 4 weeks, or placebo every 4 weeks for 12 weeks.

The researchers evaluated participants using Eczema Area and Severity Index (EASI), Investigator Global Assessment (IGA), and Scoring Atopic Dermatitis (SCORAD). The primary endpoint was a 50% reduction in EASI score from baseline (EASI-50) at week 12. EASI-75, IGA score of 0 or 1, and SCORAD-50 at week 12 were the key secondary endpoints.

At week 12, participants treated with lebrikizumab 125 mg once every 4 weeks achieved the statistically significant outcomes (P < 0.05), which include 82.4% EASI-50, 55% EASI-75, 51% SCORAD-50. The values obtained for the IGA score were not statistically significant.

Approximately 70% of individuals with moderate-to-severe AD receiving lebrikizumab combined with standard-of-care topical corticosteroids (TCS) achieved at least a 75% improvement in overall disease severity in the ADhere trial at 16 weeks. Among individuals taking lebrikizumab with TCS, approximately 41% achieved clear or almost clear skin at 16 weeks compared with 22% of individuals taking the placebo and TCS.

Additionally, at week 16, approximately 70% of individuals taking lebrikizumab and TCS achieved an EASI-75 reduction response compared with 42% for the placebo and TCS. The differences between the individuals on both combinations were observed as early as 4 weeks for EASI-75.

Individuals treated with lebrikizumab plus TCS also achieved statistically significant improvements across key secondary endpoints, including itching, interference of itching on sleep, quality-of-life measures, and skin clearance compared with the placebo and TCS.

Adverse Events (AEs)

TREBLE study participants tolerated lebrikizumab treatment well, with only 3 patients (2%) in the combined lebrikizumab group withdrawing due to AEs. Severe AEs, such as anaphylactic reactions, malignancies, protocol-defined parasitic or targeted intracellular infections of interest, or death were not reported or seen. A low incidence of injection site reactions was recorded in the lebrikizumab treatment (1.3%) arm and lasted an average of 1 to 3 days.

In the ADhere trial of lebrikizumab, investigators noted that the safety results were consistent with prior lebrikizumab studies in AD. Individuals who took lebrikizumab and TCS reported a higher frequency of AEs compared with those taking the placebo and TCS.

Most AEs were mild or moderate in severity. The AEs did not lead to the discontinuation of lebrikizumab. The most common AEs for those on lebrikizumab were conjunctivitis and headaches.

About the Author

Dannoy Gibson is a 2024 PharmD candidate at the University of Connecticut.

References

Lilly’s Lebrikizumab combined with topical corticosteroids showed significant improvements in disease severity for atopic dermatitis. Eli Lilly and Company. Accessed May 10, 2022. Lilly's Lebrikizumab Combined with Topical Corticosteroids Showed Significant Improvements in Disease Severity for Atopic Dermatitis | Eli Lilly and Company

Weidinger S, Novak N. Atopic dermatitis. Lancet. 2016;387(10023):1109-1122. doi: 10.1016/S0140-6736(15)00149-X

Silverberg JI, Thyssen JP, Fahrbach K, et al. Comparative efficacy and safety of systemic therapies used in moderate-to-severe atopic dermatitis: a systematic literature review and network meta-analysis. J Eur Acad Dermatol Venereol. 2021;35(9):1797-1810. doi: 10.1111/jdv.17351

Simpson EL, Flohr C, Eichenfield LF, et al. Efficacy and safety of lebrikizumab (an anti-IL-13 monoclonal antibody) in adults with moderate-to-severe atopic dermatitis inadequately controlled by topical corticosteroids: A randomized, placebo-controlled phase II trial (TREBLE). J Am Acad Dermatol. 2018;78(5):863-871.e11. doi: 10.1016/j.jaad.2018.01.017