Efficacy and Safety of Lebrikizumab, a High-Affinity Interleukin 13 Inhibitor, in Adults With Moderate to Severe Atopic Dermatitis

Abstract

IMPORTANCE Interleukin 13 (IL-13) is a central pathogenic mediator driving multiple features of atopic dermatitis (AD) pathophysiology.OBJECTIVE To evaluate the efficacy and safety of lebrikizumab, a novel, high-affinity, monoclonal antibody targeting IL-13 that selectively prevents formation of the IL-13Rα1/IL-4Rα heterodimer receptor signaling complex, in adults with moderate to severe AD. DESIGN, SETTING, AND PARTICIPANTSA phase 2b, double-blind, placebo-controlled, dose-ranging randomized clinical trial of lebrikizumab injections every 4 weeks or every 2 weeks was conducted from January 23, 2018, to May 23, 2019, at 57 US centers. Participants were adults 18 years or older with moderate to severe AD.INTERVENTIONS Patients were randomized 2:3:3:3 to placebo every 2 weeks or to subcutaneous injections of lebrikizumab at the following doses: 125 mg every 4 weeks (250-mg loading dose [LD]), 250 mg every 4 weeks (500-mg LD), or 250 mg every 2 weeks (500-mg LD at baseline and week 2). MAIN OUTCOMES AND MEASURESThe primary end point was percentage change in the Eczema Area and Severity Index (EASI) (baseline to week 16). Secondary end points for week 16 included proportion of patients achieving Investigator's Global Assessment score of 0 or 1 (IGA 0/1); EASI improvement of at least 50%, 75%, or 90% from baseline; percentage change in the pruritus numeric rating scale (NRS) score; and pruritus NRS score improvement of at least 4 points. Safety assessments included treatment-emergent adverse events.RESULTS A total of 280 patients (mean [SD] age, 39.3 [17.5] years; 166 [59.3%] female) were randomized to placebo (n = 52) or to lebrikizumab at doses of 125 mg every 4 weeks (n = 73), 250 mg every 4 weeks (n = 80), or 250 mg every 2 weeks (n = 75). Compared with placebo (EASI least squares mean [SD] percentage change, −41.1% [56.5%]), lebrikizumab groups showed dose-dependent, statistically significant improvement in the primary end point vs placebo at week 16: 125 mg every 4 weeks (−62.3% [37.3%], P = .02), 250 mg every 4 weeks (−69.2% [38.3%], P = .002), and 250 mg every 2 weeks (−72.1% [37.2%], P < .001). Differences vs placebo-treated patients (2 of 44 [4.5%]) in pruritus NRS improvement of at least 4 points were seen as early as day 2 in the high-dose lebrikizumab group (9 of 59 [15.3%]). Treatment-emergent adverse events were reported in 24 of 52 placebo patients (46.2%) and in lebrikizumab patients as follows: 42 of 73 (57.5%) for 125 mg every 4 weeks, 39 of 80 (48.8%) for 250 mg every 4 weeks, and 46 of 75 (61.3%) for 250 mg every 2 weeks; most were mild to moderate and did not lead to discontinuation. Low rates of injection-site reactions (1 of 52 [1.9%] in the placebo group vs 13 of 228 [5.7%] in all lebrikizumab groups), herpesvirus infections (2 [3.8%] vs 8 [3.5%]), and conjunctivitis (0% vs 6 [2.6%]) were reported.CONCLUSIONS AND RELEVANCE During 16 weeks of treatment, lebrikizumab provided rapid, dose-dependent efficacy across a broad range of clinical manifestations in adult patients with moderate to severe ...

New and Emerging Systemic Treatments for Atopic Dermatitis

“…A second phase IIb trial in adults reported similar efficacy results (Table 1) [33]. In the TREBLE study, there were no life-threatening adverse events and no adverse events showed a dose-dependent trend [32].…”

Emerging Therapeutic Options for Chronic Pruritus

“…125 mg every 4 weeks (250 mg loading dose; n = 73), 250 mg every 4 weeks (500 mg loading dose; n = 80) or 250 mg every 2 weeks (500 mg loading dose at baseline and week 2; n = 75), while 52 patients received placebo. At week 16, the mean NRS pruritus score percentage changes were − 35.9%, − 49.6%, − 60.6%, and 4.3% of patients, respectively ( p = 0.05, p < 0.001 and p < 0.001 compared with placebo, respectively) [ 101 ].…”

Dupilumab for the treatment of adolescents with atopic dermatitis

“…Tralokinumab, an anti-IL-13 antibody, has shown promising results in a phase 2b study, with a very good safety profile while also being clinically effective [59]. Lebrikizumab a monoclonal antibody targeting IL-13 has shown promising results in a phase 2b study and has demonstrated a favorable safety profile [60]. All monoclonal antibodies share the advantage that drug-drug-interactions are not an issue in a patient population which is likely to use multiple medications.…”

“…Study data presented in congresses indicate a fast onset of the anti-pruritic and anti-inflammatory effects of the JAK inhibitors. The most important side effects of JAK inhibitors are a reactivation of viral infections, thrombosis, and pulmonary emboli which should be taken seriously (60).…”