380 Patients maintain stable response with no or minimal fluctuations during treatment with lebrikizumab up to Week 52
Authors: Silverberg Jonathan I , Wollenberg Andreas  , Gold Linda Stein , Lio Peter , Carrascosa Jose Manuel  , Gallo Gaia , Casillas Marta  , Ding Yuxin , Chen Sherry , Agell Helena  , Thyssen Jacob P 
Published: June 2023

Abstract
Lebrikizumab is a monoclonal antibody that binds with high affinity and slow off-rate to interleukin (IL)-13, thereby blocking the downstream effects of IL-13 with high potency. ADvocate1 (NCT04146363) and ADvocate2 (NCT04178967) are identically designed phase 3, randomized, double-blinded, placebo-controlled trials evaluating lebrikizumab for the treatment of moderate-to-severe atopic dermatitis (AD). At Week 16 of both studies, lebrikizumab 250 mg every 2 weeks (Q2W) showed statistically significant improvements in measures of skin clearance and patient reported outcomes. Patients treated with lebrikizumab achieved clinically meaningful improvements in the signs and symptoms of AD with fewer AD flares across multiple definitions than patients treated with placebo. In patients who met the protocol-defined criteria for response to lebrikizumab at Week 16, most patients treated with lebrikizumab Q2W and lebrikizumab every 4 weeks (Q4W) maintained an Investigator’s Global Assessment (IGA) 0/1 response (71% and 77%, respectively) and a 75% improvement in the Eczema and Severity Index from baseline (EASI 75; 78% and 82%, respectively) up to Week 52. The objective of this analysis is to determine the proportion and the individual efficacy trajectory of lebrikizumab-treated patients who exhibited a stable response with no or minimal fluctuations of efficacy from Week 16 to Week 52 in Week 16 responders. Patients who responded to lebrikizumab at the end of the 16-week induction period were rerandomized 2 : 2 : 1 to receive lebrikizumab Q2W, lebrikizumab Q4W or placebo Q2W (withdrawal) for 36 additional weeks. Week 16 responders were defined as those achieving an EASI 75 or IGA 0/1 with a ≥2-point improvement and without rescue medication use. We defined no or minimal fluctuations as maintaining EASI 75 for at least 80% of the 10 study visits from Week 16 to Week 52. Separately, we analysed EASI 90 with the same criteria. We also analysed the proportion of patients who achieved each endpoint at all 10 maintenance period study visits. ADvocate2 analyses were performed on a modified population, excluding 17 patients who entered the maintenance period (from a single study site) and whose eligibility could not be confirmed. Therefore, analyses were performed on the modified pooled population of ADvocate1 and ADvocate2 patients. All analyses were performed post hoc. If patients used rescue medication, discontinued treatment or transferred to the escape arm, data collected at or after the event was imputed as nonresponse. In ADvocate1 and ADvocate2, 291 patients met the criteria for response at Week 16 (EASI 75 or IGA 0/1 with a ≥2-point improvement and without rescue medication use) and were rerandomized to receive lebrikizumab Q2W (n = 113), lebrikizumab Q4W, (n = 118) or withdrawal (n = 60) from Week 16 to Week 52. The proportions of patients who maintained EASI 75 for at least 80% of the maintenance period were 71% (lebrikizumab Q2W), 71% (lebrikizumab Q4W) and 60% (withdrawal). The proportions of patients who maintained EASI 75 at all study visits were 53% (lebrikizumab Q2W), 55% (lebrikizumab Q4W) and 38% (withdrawal). The proportions of patients to achieve and maintain the more stringent response of EASI 90 for at least 80% of study visits were 45% (lebrikizumab Q2W), 51% (lebrikizumab Q4W) and 35% (withdrawal). In ADvocate1 and ADvocate2, approximately 7 out of 10 of patients who continued treatment with lebrikizumab maintained at least an EASI 75 response with no or minimal fluctuations. These individual patient data show that most patients treated with monotherapy lebrikizumab Q2W and Q4W maintain a stable response with no or minimal fluctuations of efficacy up to Week 52.