Safety Profile of Lebrikizumab in Adults and Adolescents with Moderate-to-Severe Atopic Dermatitis: Integrated Data used in the US Prescribing Information

Introduction: Lebrikizumab was recently approved in the US for treatment of moderate-to-severe atopic dermatitis. Safety data have been reported from individual trial disclosures and multiple long-term integrated lebrikizumab analyses. Here we present integrated safety data from the US Prescribing Information. Methods: Data were summarized from three datasets: 1) Week 0–16 PBO-controlled analysis (lebrikizumab 250 mg every two weeks [LEBQ2W] versus PBO, presented as monotherapy studies [ADvocate1, NCT04146363; ADvocate2, NCT04178967; and Phase 2b KGAF, NCT03443024] and the topical corticosteroid (TCS) combination study [ADhere, NCT04250337]); 2) Maintenance period of monotherapy studies ADvocate1 and ADvocate2 (LEBQ2W-treated patients who responded at week 16 and received LEBQ2W, LEBQ4W or PBO [LEB withdrawal] to week 52); and 3) Week 0–52/56 analysis (patients treated with LEBQ2W only, or LEBQ2W then LEBQ4W up to 52 or 56 weeks). Study-size-adjusted percentages were calculated for the pooled PBO-controlled analysis and maintenance period. Exposure-adjusted incidence rates (IRs) were number of patients reporting an event per 100 patient-years at risk. Results: PBO-controlled analysis included 338 PBO-treated and 638 LEBQ2W-treated patients in the monotherapy studies and 66 PBO-treated and 145 LEBQ2W-treated patients in the TCS study. During the maintenance period 113, 118, and 60 patients received LEBQ2W, LEBQ4W, and PBO, respectively. In Week 0-52/56 analysis 844 and 147 patients received LEBQ2W and LEBQ2W/Q4W, respectively. For PBO-controlled, adverse reactions that occurred in ≥1% of LEBQ2W-treated patients in monotherapy or TCS studies, and at a higher rate than PBO, were conjunctivitis cluster (monotherapy trials: n=61 [9.6%], LEBQ2W; n=10 [3.0%], PBO; TCS trial: n=7 [4.8%], LEBQ2W; n=0, PBO); injection site reactions (monotherapy trials: n=16 [2.6%], LEBQ2W; n=4 [1.2%], PBO; TCS trial: n=4 [2.8%], LEBQ2W; n=1 [1.5%], PBO); and herpes zoster (HZ) (monotherapy trials: n=3 [0.5%], LEBQ2W; n=0, PBO; TCS trial: n=2 [1.4%] LEBQ2W; n=0, PBO). All events were nonserious; most were mild/moderate severity. No HZ events were considered opportunistic infections or led to treatment discontinuation. In the monotherapy studies, 15 (2.4%) LEBQ2W-treated and 6 (1.8%) PBO-treated patients discontinued treatment due to AEs; in the TCS study, 3 (2.1%) LEBQ2W-treated and 0 PBO-treated patients discontinued treatment due to AEs. Eosinophilia and keratitis cluster were reported in <1% of LEBQ2W-treated patients. During the maintenance period there were 2 (1.8%), 12 (10.1%) and 5 (8.3%) conjunctivitis cluster events in LEBQ2W, LEBQ4W, and PBO, respectively. Atopic keratoconjunctivitis was reported by 1 (0.8%) patient in LEBQ4W; vernal keratoconjunctivitis was reported by 1 (0.9%) patient in LEBQ2W; no events reported in PBO. In the Week 0–52/56 analysis, the IR of conjunctivitis was 18.3 for LEBQ2W and 20.6 for LEBQ2W/Q4W. Conclusions: For the adverse reactions reported in the lebrikizumab US Prescribing Information, the majority were mild to moderate in severity and few led to treatment discontinuation.