The efficacy and safety of lebrikizumab monotherapy for the management of moderate-to-severe atopic dermatitis: A systematic review and meta-analysis

Abstract

Background: Atopic 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.

Methods: Cochrane 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.

Results: Three 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.

Conclusion: Overall, 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 registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022362438.

Keywords: anti-IL-13; atopic dermatitis; eczema; lebrikizumab; monoclonal antibodies.

FIGURE 1

Study flowchart as per the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) criteria. CENTRAL, Cochrane Central Register of Controlled Trials; RCT, randomized controlled trial. *Search results on October 1, 2022. **Exclusion was done by humans exclusively.

FIGURE 2

Risk of bias graph.

FIGURE 3

Risk of bias summary.

FIGURE 4

Forest plot of EASI score. CI, confidence interval; IV, inverse variance; SMD, standardized mean difference; SD, standard deviation; Q2W, every 2 weeks; Q4W, every 4 weeks.

FIGURE 5

Grading of Recommendations Assessment, Development and Evaluation (GRADE) evidence profile. CI, confidence interval; RCT, randomized controlled trial; RR, risk ratio.

FIGURE 6

Forest plot of IGA score. CI, confidence interval; IV, inverse variance; RR, risk ratio; Q2W, every 2 weeks; Q4W, every 4 weeks.

FIGURE 7

Forest plot of the percentage change in BSA. CI, confidence interval; IV, inverse variance; SMD, standardized mean difference; SD, standard deviation; Q2W, every 2 weeks; Q4W, every 4 weeks.

FIGURE 8

Forest plot of EASI75 score. CI, confidence interval; IV, inverse variance; RR, risk ratio; Q2W, every 2 weeks; Q4W, every 4 weeks.

FIGURE 9

Forest plot of SAEs. CI, confidence interval; IV, inverse variance; RR, risk ratio; Q2W, every 2 weeks; Q4W, every 4 weeks.

FIGURE 10

Forest plot of NSAEs. CI, confidence interval; IV, inverse variance; RR, risk ratio; Q2W, every 2 weeks; Q4W, every 4 weeks.

FIGURE 11

Forest plot of mortality. CI, confidence interval; IV, inverse variance; RR, risk ratio; Q2W, every 2 weeks; Q4W, every 4 weeks.