Abstract
Abstract Introduction/Background Atopic dermatitis (AD) is a chronic disease affecting children and adults and requires long-term treatment. Moderate-to-severe AD causes itching, which considerably impacts sleep. Interleukin (IL)-13 is the key cytokine in the skin of patients with AD. Lebrikizumab (LEB) is a novel monoclonal antibody that binds with high affinity and slow off-rate to IL-13, thereby blocking the downstream effects of IL-13 with high potency. LEB has demonstrated efficacy and maintained improvement in measures of itch and sleep over 52 weeks in previous phase 3 trials. ADhere (NCT04250337) was a 16-week, randomized, double-blinded, placebo-controlled, phase 3 clinical trial, where patients were treated with LEB and topical corticosteroids (TCS) vs placebo and TCS. LEB responders from ADhere at week 16 were defined as having Investigator’s Global Assessment response of 0 or 1 or reporting 75% improvement from ADhere baseline in Eczema Area and Severity Index who did not use rescue medications. ADhere LEB responders were rerandomized 2:1 into ADjoin (NCT04392154) for blinded treatment with LEB 250 mg every 2 weeks (Q2W) or every 4 weeks (Q4W), respectively, with TCS use as needed, for an additional 100 weeks with itch and sleep data being collected for the first 52 weeks. Objectives The objectives of the study are to report the impact of LEB on itch and sleep improvements over a longer period (68 weeks) in ADhere week 16 LEB responders with moderate-to-severe AD who entered a long-term extension study, ADjoin. Methods Itch was reported using the Pruritus Numeric Rating Scale (NRS), a patient-reported, single-item, daily, 11-point scale, where the minimal clinically important difference (MCID) is 3 points. Sleep loss due to itch was reported using the Sleep-Loss Scale, a patient-reported, single-item, 5-point scale, where the MCID is 1 point. We report ≥3-point improvement in Pruritus NRS among patients with baseline score at least 3, percent change from ADhere baseline (PCFB) in Pruritus NRS, Pruritus NRS (0,1), ≥1-point improvement in Sleep-Loss Scale score among patients with baseline score at least 1, ≥2-point improvement in Sleep-Loss Scale score among patients with baseline score at least 2 and PCFB in Sleep-Loss Scale score. All outcomes were reported at week 52 of ADjoin study, after a total of 68 weeks of LEB treatment. As observed analyses used all data collected. Results At week 68, most patients reported maintaining ≥3-point improvement in Pruritus NRS treated with LEB Q2W (80.6%, 29/36) and LEB Q4W (88.9%, 16/18). Patients treated with LEB Q2W and LEB Q4W reported maintaining 65.3% and 59.4% improvement in Pruritus NRS at week 68 compared to ADhere baseline, respectively. At week 68, 45.9% (17/37) patients in LEB Q2W group and 31.6% (6/19) in LEB Q4W group reached Pruritus NRS of 0 or 1. At week 68, most patients reported maintaining ≥1-point improvement in Sleep-Loss Scale score treated with LEB Q2W (96.9%, 31/32) and LEB Q4W (85.7%, 12/14). Similarly, most patients reported maintaining ≥2-point improvement in Sleep-Loss Scale score treated with LEB Q2W (60.9%, 14/23) and LEB Q4W (75.0%, 6/8). Patients treated with LEB Q2W and Q4W reported maintaining 84.1% and 58.8% improvement in Sleep-Loss Scale score at week 68, respectively, compared to ADhere baseline. Conclusions LEB + TCS maintained itch and sleep improvement at 68 weeks in patients with moderate-to-severe atopic dermatitis.
