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. 2025 Sep;15(9):2537-2551.
doi: 10.1007/s13555-025-01479-y. Epub 2025 Jul 11.

Dupilumab versus Lebrikizumab Demonstrates Greater Likelihood of Achieving and Maintaining Improvements in Efficacy Outcomes Using a Placebo-Adjusted Indirect Treatment Comparison

Sonja Ständer  1 , Andreas Pinter  2 , Firas G Hougeir  3 , Patricia Guyot  4 , Yingxin Xu  5 , Amy H Praestgaard  6 , Nick Freemantle  7 , Ana B Rossi  6 , Gaëlle Bégo-Le-Bagousse  4 , Zhixiao Wang  5 , Kerry Noonan  6 , Mike Bastian  8
Affiliations

Dupilumab versus Lebrikizumab Demonstrates Greater Likelihood of Achieving and Maintaining Improvements in Efficacy Outcomes Using a Placebo-Adjusted Indirect Treatment Comparison

Sonja Ständer et al. Dermatol Ther (Heidelb). 2025 Sep.

Abstract

Introduction: Dupilumab and lebrikizumab have demonstrated efficacy in atopic dermatitis (AD) clinical trials; however, no direct comparisons exist.

Methods: Efficacy outcome achievement (dupilumab and lebrikizumab with topical corticosteroids [TCS]) at 16 weeks and efficacy outcomes maintenance (dupilumab and lebrikizumab monotherapy without TCS) at 52 weeks were assessed using a placebo-adjusted Bucher indirect treatment comparison (ITC). Week 16 data were sourced from LIBERTY AD CHRONOS (dupilumab, n = 106; placebo, n = 315) and ADhere (lebrikizumab, n = 145; placebo, n = 66) trials. Week 52 data were sourced from SOLO-CONTINUE (dupilumab, n = 80; placebo, n = 39) and ADvocate 1 and 2 (lebrikizumab, n = 231; placebo, n = 60) trials, including patients who had achieved ≥ 75% improvement from baseline in Eczema Area and Severity Index (EASI)-75 or Investigator's Global Assessment (IGA) score 0/1 (clear/almost clear) at week 16. Results are presented as odds ratios (ORs) with 95% confidence intervals (CIs).

Results: At week 16, patients receiving dupilumab every 2 weeks (q2w) + TCS had a significantly higher likelihood of achieving EASI-75 (OR 2.4; 95% CI 1.1-5.1) and a ≥ 4-point improvement in Peak Pruritus Numeric Rating Scale (PP-NRS; OR 2.7; 95% CI 1.2-6.0) versus those receiving lebrikizumab q2w + TCS. ORs for other endpoints (IGA-0/1 and ≥ 4-point improvement in Dermatology Life Quality Index) numerically favored dupilumab. At week 52, dupilumab q2w maintained a significantly higher OR for EASI-75 (OR 3.5; 95% CI 1.2-10.5) versus lebrikizumab every 4 weeks. ORs for EASI-90 (OR 3.3; 95% CI 1.0-11.3), IGA 0/1 (OR 3.3; 95% CI 0.7-15.1), and PP-NRS (OR 8.8; 95% CI 0.9-84.8) numerically favored dupilumab.

Conclusions: Placebo-adjusted Bucher ITC analyses showed that the likelihood of achieving efficacy outcomes at 16 weeks and maintaining efficacy outcomes at 52 weeks was higher for dupilumab versus lebrikizumab recipients.

Keywords: Atopic dermatitis; Bucher indirect treatment comparison; Dupilumab; Indirect treatment comparison; Lebrikizumab.

Plain language summary

Dupilumab and lebrikizumab are two drugs used to treat patients with moderate-to-severe atopic dermatitis (AD), a long-lasting condition that makes the skin dry, red, and itchy, affecting patients' everyday life. Both drugs work by blocking proteins that cause inflammation in the body, but differently: dupilumab blocks two proteins (interleukin-4 and interleukin-13) by targeting their receptor, while lebrikizumab blocks one protein (interleukin-13) directly. Several studies compared each drug with a placebo (inactive drug) with/without prescription skin creams (topical corticosteroids), but no studies have compared them with each other. We wanted to understand which drug might be more effective in treating AD, both short term and long term. We compared data from studies where each drug was tested against a placebo group, allowing us to indirectly compare the two drugs using a scientific method: "placebo-adjusted indirect treatment comparison". Two 16-week studies were used to understand the short-term effects when patients used dupilumab or lebrikizumab with prescription skin creams. For long-term effects, we used data from studies that included patients who got better at week 16 with either dupilumab or lebrikizumab, continued treatment up to week 52, and did not use prescription skin creams. Our results showed that in the short-term studies, patients treated with dupilumab had a better chance of improving how itchy their skin felt, the number of skin sores, and overall well-being, compared with those treated with lebrikizumab. In addition, patients who got better with dupilumab were more likely to maintain these improvements over 1 year compared with patients treated with lebrikizumab.

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Conflict of interest statement

Declarations. Conflict of Interest: Sonja Ständer declares receiving research grants from Almirall, Galderma, Sanofi, and Trevi Therapeutics; has been a consultant for AbbVie, Almirall, Amgen, BMS, Beiersdorf, Clexio, Galderma, Kiniksa, Klinge Pharma, KliRNA, P.G. Unna Academy, Pfizer, Sanofi, and Vifor; has served as an advisory board member for AbbVie, Almirall, Celldex, Galderma, Lilly, P.G. Unna Akademie e. V., Pfizer, Regeneron Pharmaceuticals Inc., Sanofi, and Vifor; and has served as a speaker for AbbVie, Almirall, Amgen, Beiersdorf, Focus Insight, FOMF, GCI Health, Galderma, LEO Pharma, Lilly, L’Oréal, MEDahead, Medicinske Tidsskrifter, Novartis, P.G. Unna Academy, Pfizer, Sanofi, STREAMED UP, touchIME, UCB, and Vifor. Andreas Pinter has involved in clinical trials for AbbVie, Almirall Hermal, Amgen, Biogen Idec, BioNTech, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Galderma, GSK, Hexal, Janssen, Klinge Pharma, LEO Pharma, MC2 Pharma, Medac, Merck Serono, Mitsubishi Tanabe Pharma, MSD, Novartis, Pascoe, Pfizer, Regeneron Pharmaceuticals Inc., Roche, Sandoz, Sanofi, Schering-Plough, Tigercat Pharma, UCB Pharma, and Zuellig Pharma; declares receiving speaker fees from AbbVie, Almirall Hermal, Amgen, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Galderma, Janssen, Klinge Pharma, LEO Pharma, Medac, Novartis, Pfizer, Sanofi, UCB Pharma, and Zuellig Pharma; and has received grants from AbbVie and Almirall. Firas G. Hougeir has been a consultant/speaker for AbbVie, Apogee, Galderma, LEO, Lilly, Pfizer, Sanofi, and Regeneron Pharmaceuticals Inc.; and investigator for Apogee, Galderma, LEO, and Lilly. Nick Freemantle has received grants from Cure Parkinson’s Trust, European Union, Medical Research Council, and National Institute for Health and Care Research; consultancy fees from Abbott, Aimmune Therapeutics, ALK, AstraZeneca, Galderma, Gedeon Richter, Ipsen, Novo Nordisk, Sanofi, Théa Pharma, and Vertex Pharmaceuticals; and honorarium from Abbott Singapore. Patricia Guyot, Amy H. Praestgaard, Ana B. Rossi, Gaëlle Bégo-Le-Bagousse, Kerry Noonan, and Mike Bastian are employees of Sanofi, and may hold stock and/or stock options in the company. Yingxin Xu and Zhixiao Wang are employees and shareholders of Regeneron Pharmaceuticals Inc. Ethical Approval: This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.

Figures

Fig. 1
Fig. 1
Placebo-anchored Bucher ITC results for efficacy outcomes at week 16 in patients who received TCS. *Statistically significant in favor of dupilumab. aNumerically in favor of dupilumab. Log scale is used. DLQI Δ ≥ 4 Improvement in Dermatology Life Quality Index of at least 4 from baseline, EASI Eczema Area and Severity Index, IGA Investigator’s Global Assessment, ITC indirect treatment comparison, PP-NRS Δ ≥ 4 Improvement in Peak Pruritus Numeric Rating Scale of at least 4 from baseline, q2w every 2 weeks, TCS topical corticosteroid(s)
Fig. 2
Fig. 2
Placebo-anchored Bucher ITC results for maintenance of efficacy outcomes at week 52 in patients receiving monotherapy. *Statistically significant in favor of dupilumab. aNumerically in favor of dupilumab. Log scale is used. EASI Eczema Area and Severity Index, EASI-75/90 75%/90% improvement from baseline in EASI, IGA Investigator’s Global Assessment, PP-NRS Δ ≥ 4 Improvement in Peak Pruritus Numeric Rating Scale of at least 4 from baseline, q2w every 2 weeks, q4w every 4 weeks
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