Efficacy and Safety Evaluation of Different Lebrikizumab Dosages in Atopic Dermatitis Patients Over 16 to 24 Weeks: A <scp>BIOREP</scp> Registry Analysis

Lebrikizumab, a novel anti-interleukin-13 antibody, is the first biologic therapy for atopic dermatitis (AD) that offers flexible dosing for patients with inadequate disease control [1-3]. Lebrikizumab is administered every 2 weeks (Q2W) until Week 16 or beyond, contingent upon a satisfactory clinical response. Maintenance administration is conducted every 4 weeks (Q4W). In the registrational clinical trials, patients who did not achieve adequate disease control (defined as failing to achieve a 75% or greater improvement in their Eczema Area and Severity Index score [EASI-75] or an Investigator's Global Assessment [IGA] score of 0/1 at Week 16) continued to receive increased dosages through Week 24 of the trial. Among these patients, 58% who continued with the Q2W dosing regimen achieved EASI-75 in Week 24 [3]. This study evaluates the effectiveness and safety of varying lebrikizumab dosages from Weeks 16 to 24 in patients with moderate-to-severe AD, using data from the Czech BIOREP registry. Patients who discontinued treatment within the first 16 weeks of therapy were excluded from this analysis. During the study period, patients used moisturizers and various topical therapies. Among the 198 patients, 84 (42.4%) were classified as having inadequate disease control at Week 16, and Q2W dosing was maintained through Week 24. The baseline characteristics of patients in both groups were similar (Table 1). In patients receiving Q4W dosing, the mean EASI score remained unchanged after 16 (3.7) and 24 weeks (3.6). Patients continuing Q2W dosing had a higher mean EASI score after 16 weeks (7.4). By Week 24, a slight improvement was observed (6.0) (Figure 1). Similarly, in patients administered Q4W dosing, the mean Dermatology Life Quality Index [DLQI] (4.5 vs. 4.1) and mean Itch Numeric Rating Scale (NRS) score (2.4 vs. 2.4) remained stable at 16 and 24 weeks of treatment. At treatment Weeks 16 and 24, the mean DLQI (6.9 vs. 5.6) and mean Itch NRS (3.5 vs. 3.2) values showed a slight decrease in patients receiving Q2W dosing. At least one treatment-emergent adverse event was reported in 8.6% (17/198) of patients within the first 16 weeks of treatment (Q2W dosing). Conjunctivitis was observed in 15 (7.6%) patients, and hair loss was reported by 2 (1.0%) patients. Between weeks 16 and 24, conjunctivitis developed in 7.6% (6 of 79) of patients receiving Q2W dosing and in only 1.0% (1/104) of patients receiving Q4W dosing. The analysis of baseline demographic and disease-specific characteristics revealed no differences between patients with and without sufficient disease control at Week 16, including those with previous systemic therapy failure or baseline disease severity. The study by Hagino et al. [4] suggests that specific laboratory parameters may predict response to lebrikizumab. In real-world practice (similar to our study), a broader definition of insufficient disease control enables physicians to maintain higher dosages not only when there is inadequate improvement in the inflammatory skin manifestations of AD, but also when itch control is inadequate or quality of life remains poor. The analysis supported this intention, demonstrating that continued Q2W dosing in patients with inadequate disease control at Week 16 improved skin lesions, pruritus, and overall quality of life. Thus, only 7.1% (6/84) of these patients discontinued lebrikizumab at Week 24 due to insufficient disease control. Our analysis revealed that the incidence of conjunctivitis was comparable during the first 16 weeks of treatment (Q2W dosing) and between Weeks 16 and 24 in patients who remained on Q2W dosing. Conversely, patients who maintained Q4W dosing after Week 16 showed a significant reduction in the incidence of new conjunctivitis. The main limitation of this analysis is the assessment of adequate disease control, which may vary between physicians. This analysis suggests that continued lebrikizumab Q2W administration provided disease control, including for patients who did not achieve it at Week 16, whereas Q4W dosing effectively maintained the existing response. The authors have nothing to report. All of the ethics committees of the participating centres have approved the BIOREP registry. Informed consent for participation in the BIOREP registry was obtained from all the subjects involved in the analysis. Filip Rob has received consultancy and/or speaker's honoraria from and/or participated in clinical trials sponsored by AbbVie, Almirall, Amgen, ArgenX, Boehringer Ingelheim, Bristol Myers Squibb, Celldex, Eli Lilly, Johnson & Johnson, Leo Pharma, MSD, Novartis, Pfizer, Sanofi, and UCB. Martina Kojanová has received consultancy and/or speaker's honoraria from and/or participated in clinical trials sponsored by AbbVie, Almirall, Amgen, BMS, Eli Lilly, Janssen, Leo Pharma, Novartis, Pfizer, Sanofi, and UCB. Jana Třešňák Hercogová has received consultancy and/or speaker's honoraria from and/or participated in clinical trials sponsored by AbbVie, Almirall, Amgen, Eli Lilly, Fresenius Medical Care, Johnson & Johnson, Leo Pharma, MSD, Novartis, Sanofi-aventis, Sanofi Genzyme, UCB and is a co-owner of Dermatology Prof. Hercogova. Jiří Horažďovský has received consultancy and/or speaker's honoraria from and/or participated in clinical trials sponsored by AbbVie, Almirall, BMS, Eli Lilly, Johnson and Johnson, Leo Pharma, MSD, Novartis, Pfizer, Sanofi, and UCB. Yvetta Vantuchová has received consultancy and/or speaker's honoraria from and/or participated in clinical trials sponsored by AbbVie, Almirall, Amgen, BMS, Eli Lilly, Johnson & Johnson, LEO Pharma, Novartis, Sanofi, Pfizer, and UCB. Marie Jandová has received consultancy and/or speaker's honoraria from and/or participated in clinical trials sponsored by AbbVie, Almirall, Eli Lilly, Johnson and Johnson, Novartis, and UCB. Kateřina Hrazdírová has received consultancy and/or speaker's honoraria from and/or participated in clinical trials sponsored by AbbVie, Almirall, Leo Pharma, Sanofi, and UCB. Miroslav Nečas has received consultancy and/or speaker's honoraria from and/or participated in clinical trials sponsored by AbbVie, Almirall, BMS, Eli Lilly, Johnson and Johnson, Leo Pharma, Novartis, and UCB. David Stuchlík has received consultancy and/or speaker's honoraria from and/or participated in clinical trials sponsored by Almirall, Bristol Myers Squibb, Eli Lilly, Johnson and Johnson, Leo Pharma, Novartis, Pfizer, Sanofi, and UCB. Spyridon Gkalpakiotis has received consultancy and/or speaker's honoraria from and/or participated in clinical trials sponsored by AbbVie, Almirall, Alumis, Amgen, Boehringer Ingelheim, DICE, Eli Lilly, Johnson and Johnson, LEO Pharma, Novartis, Nektar, Pfizer, Sanofi, Takeda, and UCB. The other authors declare no conflicts of interest. The data that support the findings of this study are available from the corresponding author upon reasonable request.