作者
Jonathan I. Silverberg,Lindsay Ackerman,Jerry Bagel,Linda Stein Gold,Andrew Blauvelt,David Rosmarin,Raj Chovatiya,Matthew Zirwas,Gil Yosipovitch,Jill Waibel,Jenny E. Murase,B. Lockshin,Jamie Weisman,Amber Reck Atwater,Jennifer Proper,Maria Silk,Evangeline Pierce,Maria Lucia Buziqui Piruzeli,Sonia Montmayeur,Christopher F. Schuster
摘要
ADapt (NCT05369403), an open-label, Phase 3b, 24-week study, evaluated the efficacy and safety of lebrikizumab (LEB) in patients with moderate-to-severe atopic dermatitis (AD) previously treated with dupilumab (DUPI). Patients must have discontinued DUPI due to inadequate response (non-response, partial response, or loss of response), intolerance or an adverse event (AE), or other reasons. Four or more weeks after discontinuing DUPI, patients received a 500-mg LEB loading dose at Baseline and at Week 2 followed by 250 mg every 2 weeks through Week 16 (Q2W). At Week 16, responders (IGA 0 or 1 with ≥2-point improvement (IGA0,1) or EASI75 [primary endpoint]) received LEB 250 mg once every 4 weeks (Q4W); other patients continued with 250 mg Q2W. Q2W and Q4W data were pooled and analyzed as-observed and with nonresponder/multiple imputation (NRI/MI). Among 86 enrolled patients, 56% discontinued DUPI due to inadequate response, 16% due to intolerance/AEs to DUPI, and 28% for other reasons. For all patients, at Weeks 16 and 24, respectively, proportions of patients achieving: 1) EASI75: 57.4% and 60.0%, as-observed; 50.7% and 52.8% NRI/MI; 2) IGA0,1: 38.7% and 38.2%, as-observed; 35.6% and 36.8%, NRI/MI; 3) Face-IGA 0: 42% and 49%, as-observed; 4) Pruritus NRS ≥4-point improvement 53.2% and 61.5% as-observed; 48.8% and 47.9% NRI/MI; and 5) DLQI ≥4-point improvement 83.0% and 83.0% as-observed. The safety profile was consistent with other LEB Phase 3 trials. Four patients who discontinued DUPI due to conjunctivitis did not report conjunctivitis with LEB. 3.5% of patients reported treatment-emergent conjunctivitis. In DUPI-experienced patients, treatment of moderate-to-severe AD with LEB resulted in meaningful improvements in skin clearance, itch, and quality of life.