Lebrikizumab vs Other Systemic Monotherapies for Moderate-to-Severe Atopic Dermatitis: Network Meta-analysis of Efficacy

Abstract

Introduction: A systematic literature review and network meta-analysis (NMA) were conducted to compare the short-term efficacy of lebrikizumab to other biologic and Janus kinase (JAK) inhibitor monotherapies approved for moderate-to-severe atopic dermatitis in adults and adolescents.

Methods: The NMA included randomized, double-blind, placebo-controlled monotherapy phase 2 and 3 trials of biologics (lebrikizumab 250 mg every 2 weeks [Q2W], dupilumab 300 mg Q2W, and tralokinumab 300 mg Q2W) and JAK inhibitors (abrocitinib 100/200 mg daily, baricitinib 2/4 mg daily, and upadacitinib 15/30 mg daily) at approved doses. Efficacy outcomes included the proportions of patients achieving Eczema Area and Severity Index (EASI) improvement, an Investigator Global Assessment of 0 or 1 (IGA 0/1), and a ≥ 4-point improvement in pruritus/itch numeric rating scale score at 12 weeks (abrocitinib) or 16 weeks (other treatments). Itch was also assessed at week 4. A Bayesian NMA employing baseline risk-adjusted random effects models was used to estimate treatment differences.

Results: Twenty-two monotherapy studies involving 8531 patients were included in the NMA. By week 12/16, lebrikizumab had superior odds of achieving IGA 0/1 and itch improvement compared to baricitinib and tralokinumab; similar odds to dupilumab, abrocitinib, and upadacitinib 15 mg; and inferior odds to upadacitinib 30 mg. Additionally, lebrikizumab had a higher probability of improving EASI than baricitinib 2 mg; similar probability to baricitinib 4 mg, tralokinumab, dupilumab, abrocitinib, and upadacitinib 15 mg; and lower probability than upadacitinib 30 mg daily. At week 4, lebrikizumab had superior odds of improving itch compared to tralokinumab; similar odds to baricitinib, dupilumab, and abrocitinib 100 mg; and inferior odds to abrocitinib 200 mg and upadacitinib.

Conclusion: Among biologics, lebrikizumab was comparable to dupilumab and superior to tralokinumab in improving response rates at week 16. Upadacitinib 30 mg was the only JAK inhibitor with superior response rates compared to lebrikizumab.

Keywords: Atopic dermatitis; Eczema Area and Severity Index; Investigator Global Assessment; Lebrikizumab; Network meta-analysis; Pruritus/itch Numeric Rating Scale.

Fig. 1

PRISMA diagram for the SLR. Fifty-three unique studies were identified by the SLR and assessed for their eligibility to be included in NMAs. Studies that did not report on a lebrikizumab dose of interest or an intervention or dose not approved by the European Medicines Agency or US Food and Drug Administration for AD were excluded. To ensure appropriate study design, extension studies or studies with a non-randomized initial treatment period were excluded. To remove bias arising from absence of a placebo control arm, studies that were not placebo controlled were excluded. Studies that did not report data on outcomes of interest were excluded. Twenty-two monotherapy studies were eligible for inclusion in NMAs. AD, atopic dermatitis; NMA, network meta-analysis; PRISMA, Preferred Reporting Items for Systematic Review and Meta-Analyses; SLR, systematic literature review

Fig. 2

Network meta-analysis diagram. This NMA diagram shows the network for EASI response and IGA 0/1 response. The network for ≥ 4-point reduction in pruritus/itch NRS at week 16 is identical, except without the ECZTRA 5 and JADE MOA trials. The network for ≥ 4-point reduction in pruritus/itch NRS at week 4 is similar except without the ECZTRA 5, JADE MOA, NCT03912259, NCT01859988, and NCT02925117 trials. EASI, eczema area and severity index; IGA, Investigator Global Assessment; NMA, network meta-analysis; NRS, numeric rating scale; QD, daily; Q2W, every 2 weeks

Fig. 3

IGA 0/1 response relative to lebrikizumab at week 12/16. The forest plot was derived from Bayesian NMA using a baseline-risk adjusted RE model. Results are given as ORs and 95% CrIs for each comparator treatment versus lebrikizumab. For each trial, endpoints were measured at the primary endpoint timepoint (i.e., week 12 for abrocitinib and week 16 for all other treatments). CrI, credible interval; IGA, investigator global assessment; NMA, network meta-analysis; OR, odds ratio; QD, daily; Q2W, every 2 weeks; RE, random effects

Fig. 4

Probability (95% CrI) of achieving EASI response at week 12/16. The bar graph shows the absolute probability of achieving EASI 50, 75, and 90, along with the corresponding 95% CrIs, using a baseline-risk adjusted RE model. For each trial, endpoints were measured at the primary endpoint timepoint (i.e., week 12 for abrocitinib and week 16 for all other treatments). CrI, credible interval; EASI, Eczema Area and Severity Index; QD, daily; Q2W, every 2 weeks; RE, random effects

Fig. 5

≥4 point reduction in pruritus/itch NRS response relative to lebrikizumab. The forest plot was derived from Bayesian NMA using a baseline-risk adjusted RE model. Results are given as ORs and 95% CrIs for each comparator treatment versus lebrikizumab. a Pruritus/itch NRS response at week 4. b Pruritus/itch NRS response at week 12/16. For each trial, endpoints were measured at the primary endpoint timepoint (i.e., week 12 for abrocitinib and week 16 for all other treatments). CrI, credible interval; NMA, network metaanalysis; NRS, numeric rating scale; OR, odds ratio; QD, daily; Q2W, every 2 weeks; RE, random effects