Two Phase 3 Trials of Lebrikizumab for Moderate-to-Severe Atopic Dermatitis

Silverberg, Jonathan I.; Guttman‐Yassky, Emma; Thaçi, Diamant; Irvine, Alan D.; Gold, Linda Stein; Blauvelt, Andrew; Simpson, Eric L.; Chu, Chia‐Yu; Liu, Zhuqing; Lima, Renata Gontijo; Pillai, Sreekumar; Sénéschal, Julien

doi:10.1056/nejmoa2206714

Cited by 88 publications

(44 citation statements)

References 50 publications

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“…The findings in this study for week 52 line up well with reported findings from the induction phase. In the ADvocate 1 & 2 studies, 58.8% and 52.1% of participants achieved EASI-75 over the 16 week induction phase, respectively, while 43.1% and 33.2% achieved IGA 0/1 with at least 2-point improvement, respectively [ 40 ]. This is very similar to the reported findings for week 16 after administration of 300 mg dupilumab Q2W in the SOLO 1 and 2 trials, where 52.5% and 48.1% achieved EASI-75, respectively, and 37.2% and 36.4% achieved IGA 0/1 with at least a 2-point improvement, respectively [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

Matching-Adjusted Indirect Comparison of the Long-Term Efficacy Maintenance and Adverse Event Rates of Lebrikizumab versus Dupilumab in Moderate-to-Severe Atopic Dermatitis

Rand,

Ramos-Goñi,

Akmaz

et al. 2023

Dermatol Ther (Heidelb)

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Introduction Lebrikizumab and dupilumab are monoclonal antibodies approved for treating moderate-to-severe atopic dermatitis (AD). Both have demonstrated efficacy and safety over the 16-week SOLOs and ADvocate trials. However, AD is a chronic and relapsing inflammatory disease, and the long-term maintenance of efficacy is critical for achieving disease control from the perspective of patients, physicians, and regulatory agencies. This study aims to compare the long-term efficacy and safety of lebrikizumab every 4 weeks (Q4W) and dupilumab every week or every 2 weeks (QW/Q2W) among adult patients who have achieved treatment efficacy following the induction period of 16 weeks. Methods Lebrikizumab’s efficacy was assessed using individual patient data (IPD) from the ADvocate 1 and 2 monotherapy trials. Dupilumab’s efficacy was evaluated using aggregate data from the adult-exclusive SOLO-CONTINUE trial. Due to the absence of a common comparator trial arm, we employed an unanchored matching-adjusted indirect comparison (MAIC), a robust methodology widely accepted by health technology assessment (HTA) agencies. This re-weights ADvocate IPD to align with SOLO-CONTINUE’s prognostic factors and effect modifiers. We compared lebrikizumab’s adjusted outcomes with dupilumab outcomes at week 52, focusing on 75% improvement in the Eczema Area and Severity Index from baseline (EASI-75), Investigator’s Global Assessment (IGA) score of 0 or 1, and overall adverse event (AE) rates. Sensitivity analyses were conducted to test various combinations of matching variables. Results Adults on lebrikizumab Q4W were more likely to maintain IGA 0/1 through the 36-week maintenance period (weeks 16–52) compared with those on dupilumab QW/Q2W [risk ratio (RR) 1.334; 95% confidence interval (CI) 1.02–1.74; p = 0.035]. Both treatments demonstrated comparable efficacy in terms of EASI-75 maintenance (RR 0.937; 95% CI 0.78–1.13; p = 0.490) and similar AE rates (RR 1.052; 95% CI 0.90–1.23; p = 0.526). Sensitivity analyses substantiated these findings. Conclusions Our findings suggest that lebrikizumab Q4W may provide equal or superior long-term maintenance of efficacy measured with EASI-75 and IGA 0/1 compared with dupilumab QW/Q2W, with the advantage of requiring less frequent doses. Supplementary Information The online version contains supplementary material available at 10.1007/s13555-023-01058-z.

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Section: Discussionmentioning

confidence: 99%

Matching-Adjusted Indirect Comparison of the Long-Term Efficacy Maintenance and Adverse Event Rates of Lebrikizumab versus Dupilumab in Moderate-to-Severe Atopic Dermatitis

Rand,

Ramos-Goñi,

Akmaz

et al. 2023

Dermatol Ther (Heidelb)

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“…IL-13 is critical in the pathogenesis of AD and IL-13 blockade is sufficient to ameliorate AD, as evidenced by the efficacy of tralokinumab and lebrikizumab for moderate-to-severe AD. 11 , 13 The impact of additionally blocking IL-4 in terms of efficacy and adverse reactions remains unclear. Although not mentioned in the original phase 3 clinical trial results, AEs such as dupilumab-associated inflammatory arthritis have emerged in the postmarketing period; these phenomena, as well as conjunctivitis, have been theorized to relate to the effect of IL-4 blockade “unmasking” or shifting the overall immune milieu toward the T helper 1 (Th1) or Th17 axis due to its critical role in Th2 differentiation.…”

Section: Discussionmentioning

confidence: 99%

A retrospective multicenter case series of real-world tralokinumab use in dupilumab-experienced patients

Herman,

Burgy,

Shahriari

2024

JAAD Case Reports

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“…Tralokinumab IL-13 Moderate-to-severe AD (approved) [122]; asthma (phase III; terminated due to presenting inconsistent effect) [123] Lebrikizumab IL-13 Moderate-to-severe AD (approved) [124]; asthma (phase III; terminated due to presenting inconsistent effect) [125] Anrukinzumab IL-13 Asthma (phase II; terminated due to lack of efficacy) VAK694 IL-4 AR (phase II; terminated due to no additional benefit) [126] Pascolizumab IL-4 Asthma (phase II; terminated due to no significant reduction in serum IgE) [127] Abbreviations: ABPA, allergic bronchopulmonary aspergillosis; AD, atopic dermatitis; AERD, aspirin exacerbated respiratory disease; AFRS, allergic fungal rhinosinusitis; AKC, atopic keratoconjunctivitis; EoE, eosinophilic esophagitis.…”

Section: Il-4rαmentioning

confidence: 99%

IL‐4/IL‐13 pathway in nasal type 2 inflammation: The central role and targeted therapy

Zhu,

Zhao,

Wang

2024

Eye & ENT Research

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Type 2 dominant inflammation in nasal mucosa is the key underlying pathophysiological mechanism of allergic rhinitis (AR) and most presentations of chronic rhinosinusitis with nasal polyps (CRSwNP). Interleukin‐4 (IL‐4) and IL‐13 share common receptor subunits and signaling molecules, which lead to various pathological changes in different cells, playing key roles in the pathogenesis of nasal type 2 inflammation. Numerous clinical trials have shown that biologics targeting key molecules of the IL‐4/IL‐13 pathway, especially IL‐4 receptor alpha, can treat CRSwNP and AR with high efficacy, and are generally well tolerated. Several biologics have been approved for the treatment of difficult‐to‐control CRSwNP, while others also show promising results. Here, we review the IL‐4/IL‐13 pathway, its role in nasal type 2 inflammation, and current targeted therapies related to the IL‐4/IL‐13 pathway, with a focus on AR and CRSwNP.

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Two Phase 3 Trials of Lebrikizumab for Moderate-to-Severe Atopic Dermatitis

Cited by 88 publications

References 50 publications

Matching-Adjusted Indirect Comparison of the Long-Term Efficacy Maintenance and Adverse Event Rates of Lebrikizumab versus Dupilumab in Moderate-to-Severe Atopic Dermatitis

Matching-Adjusted Indirect Comparison of the Long-Term Efficacy Maintenance and Adverse Event Rates of Lebrikizumab versus Dupilumab in Moderate-to-Severe Atopic Dermatitis

A retrospective multicenter case series of real-world tralokinumab use in dupilumab-experienced patients

IL‐4/IL‐13 pathway in nasal type 2 inflammation: The central role and targeted therapy

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