Lebrikizumab 250mg/2ml solution for injection pre-filled syringes

BackgroundLebrikizumab, an IL-13 immunomodulator, has shown recommendable effectiveness and safety in clinical studies for the treatment of moderate-to-severe atopic dermatitis (AD) in adolescents and adults.ObjectiveTo evaluate the efficacy and safety of lebrikizumab in the treatment of moderate-to-severe AD through a meta-analysis.MethodsPubMed, Embase, Web of Science, Medline, and ClinicalTrials.gov databases were searched up to 8 August 2023. Randomized clinical trials of lebrikizumab treatment for moderate-to-severe AD were included by screening titles, abstracts, and papers.ResultsFive studies involving 1,551 patients with AD were identified. Pooled analysis revealed significant improvements in the Eczema Area and Severity Index (EASI) score (SMD = −0.527; 95% CI = [−0.617, −0.436]), Investigator’s Global Assessment (IGA) score (RR = 2.122; 95% CI = [1.803, 2.496]), Body Surface Area (BSA) score (SMD = −0.608; 95% CI = [−1.099, −0.118]), SCORing Atopic Dermatitis (SCORAD) score (SMD = −0.441; 95% CI = [−0.633, −0.250]). Moreover, Pruritus Numeric Rating Scale (P-NRS) score, Patient-oriented Eczema Measure (POEM) scores, Sleep-loss score and Dermatology Life Quality Index (DLQI) scores showed similar results. Adverse events (AEs) (RR = 0.984; 95% CI = [0.907, 1.068]) for lebrikizumab showed no statistically significant difference compared to placebo, with similar results for serious adverse events (SAEs) (RR = 0.748; 95% CI = [0.410, 1.364]).ConclusionThis meta-analysis reveals that lebrikizumab has higher efficacy and safety in the treatment of moderate-to-severe AD, with the 250 mg Q2W dosage regimen appearing to be more advantageous.

Abstract licence: CC BY 4.0

BackgroundAtopic dermatitis (AD) is a chronically relapsing disease. Few biologics are approved for moderate-to-severe AD, and novel interventions are emerging. We aimed to evaluate the safety and efficacy of lebrikizumab, an IL-13 immunomodulator, as monotherapy vs. placebo in treating moderate-to-severe AD.MethodsCochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase, and ClinicalTrials.gov registry (CT.gov) databases were systematically searched. We evaluated lebrikizumab vs. placebo and measured efficacy using Eczema Area and Severity Index (EASI), Body Surface Area (BSA), and Investigator’s Global Assessment (IGA) change from baseline to week 16. Safety was evaluated by the incidence of serious adverse events (SAEs), non-serious adverse events (NSAEs), and mortality. The risk of bias was investigated using the Revised Cochrane risk of bias tool.ResultsThree RCTs (n = 1,149) included 543 (47.25%) men vs. 606 (52.75%) women. Meta-analysis showed statistically significant improvement in EASI, IGA, and BSA. EASI75 at week 16 for all regimens was (RR = 2.62, 95% CI [2.06, 3.34], p < 0.00001) with the first regimen (500 mg loading dose then 200 mg every 2 weeks) showing the most significant improvement (RR = 3.02, 95% CI [2.39, 3.82], p < 0.00001). The pooled analysis of safety outcomes concluded that lebrikizumab did not correlate significantly with the incidence of SAEs, NSAEs, and mortality.ConclusionOverall, lebrikizumab showed a significant improvement in all efficacy outcomes. Additionally, it did not contribute to any significant incidence of SAEs, NSAEs, or mortality. The risk of bias in included RCTs was minor except in the randomization domain. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) assessment of the outcomes ranged from low to high, but predominantly high certainty of evidence.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42022362438.

Abstract licence: CC BY 4.0

Biologic therapies targeting maladaptive type 2 inflammation have transformed the management of moderate‑to‑severe atopic dermatitis (AD); however, comparative evidence integrating both approved and next‑generation investigational agents remains limited. This Bayesian network meta‑analysis (BNMA) provides the first unified evaluation of all biologic monoclonal antibodies approved as monotherapy for AD (dupilumab, lebrikizumab, tralokinumab) together with emerging immunotherapies, including amlitelimab, rademikibart, rezpegaldesleukin, rocatinlimab, telazorlimab, temtokibart, and zumilokibart, across key efficacy measures.  A PRISMA‑2020-compliant systematic review and PROSPERO‑registered protocol (CRD420251162704) identified phase 2-3 randomized, double‑blind, placebo‑controlled trials reporting week‑16 outcomes (week‑24 for rocatinlimab). A Bayesian random‑effects NMA estimated relative risks (RRs) for EASI‑75, EASI‑90, IGA‑AD 0/1, and ≥4‑point improvement in itch Numeric Rating Scale (NRS). Treatment hierarchy was evaluated using both Bayesian (SUCRA) and frequentist (P‑score) approaches. Seventeen randomized controlled trials (RCTs) involving more than 6,000 patients were included in the analysis. Dupilumab demonstrated the most consistent and reliable efficacy across all evaluated endpoints, including improvements in EASI-75, EASI-90, IGA-AD 0/1, and itch NRS. Among investigational therapies, rocatinlimab showed a notable signal for deep clinical responses, although the available evidence remains limited and less precise. Other emerging agents, including rademikibart, temtokibart, and zumilokibart, demonstrated encouraging efficacy profiles, whereas telazorlimab showed comparatively modest clinical benefit. Ranking analyses consistently positioned dupilumab as the most reliable and highest-performing therapy overall, followed by rocatinlimab. Overall, biologic therapies were generally well tolerated in the short term; however, dupilumab remains the only agent supported by extensive long-term safety data extending up to a decade. This analysis relied on indirect comparisons anchored to short‑term placebo‑controlled induction periods, limiting assessment of long‑term safety and durability, particularly for mechanistically distinct agents such as rezpegaldesleukin, a regulatory T cell (Treg) pathway agonist, and rocatinlimab, an OXO pathway inhibitor. Evidence for several emerging therapies was restricted to small phase 2 trials, resulting in wide credible intervals (Crls) and lower certainty in comparative rankings. Trial heterogeneity in baseline severity, ethnic composition, and geographic setting may have introduced residual confounding despite sensitivity and meta‑regression analyses. These factors should be considered when interpreting relative efficacy estimates This NMA demonstrates that dupilumab remains the most reliable and effective biologic monotherapy for moderate‑to‑severe AD, supported by the greatest precision, reproducibility, and long‑term safety. Rocatinlimab shows promising investigational efficacy but requires efficacy and long-term safety validation. Zumilokibart, rademikibart, and temtokibart emerge as additional candidates with encouraging activity, whereas telazorlimab showed limited clinical benefit. Collectively, these findings provide a comprehensive comparative framework to inform biologic selection and therapeutic sequencing.

Abstract licence: CC BY