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Clinical Trial
. 2023 Feb 1;159(2):182-191.
doi: 10.1001/jamadermatol.2022.5534.

Efficacy and Safety of Lebrikizumab in Combination With Topical Corticosteroids in Adolescents and Adults With Moderate-to-Severe Atopic Dermatitis: A Randomized Clinical Trial (ADhere)

Eric L Simpson  1 , Melinda Gooderham  2 , Andreas Wollenberg  3   4 , Stephan Weidinger  5 , April Armstrong  6 , Jennifer Soung  7 , Silvia Ferrucci  8 , Renata Gontijo Lima  9 , Michael M Witte  9 , Wen Xu  9 , Hany ElMaraghy  9 , Chitra R Natalie  9 , Evangeline Pierce  9 , Andrew Blauvelt  10 ; ADhere Investigators
Collaborators, Affiliations
Clinical Trial

Efficacy and Safety of Lebrikizumab in Combination With Topical Corticosteroids in Adolescents and Adults With Moderate-to-Severe Atopic Dermatitis: A Randomized Clinical Trial (ADhere)

Eric L Simpson et al. JAMA Dermatol. .

Erratum in

  • Errors in Figure 2 and Table 2 Footnotes.
    [No authors listed] [No authors listed] JAMA Dermatol. 2023 Sep 1;159(9):1014. doi: 10.1001/jamadermatol.2023.2199. JAMA Dermatol. 2023. PMID: 37466974 Free PMC article. No abstract available.

Abstract

Importance: Lebrikizumab (LEB), a high-affinity monoclonal antibody targeting interleukin (IL)-13, demonstrated efficacy and safety in patients with moderate-to-severe atopic dermatitis (AD) during 16 weeks of monotherapy in a phase 2b trial, and two 52-week phase 3 trials.

Objective: To evaluate efficacy and safety of LEB combined with low- to mid-potency topical corticosteroids (TCS) in patients with moderate-to-severe AD.

Design, setting, and participants: The ADhere trial was a 16-week randomized, double-blinded, placebo (PBO)-controlled, multicenter, phase 3 clinical trial conducted from February 3, 2020, to September 16, 2021. The study was conducted at 54 outpatient sites across Germany, Poland, Canada, and the US and included adolescent (aged ≥12 to <18 years weighing ≥40 kg) and adult patients with moderate-to-severe AD. The treatment allocation ratio was 2:1 (LEB:PBO).

Interventions: Overall, 211 patients were randomized to subcutaneous LEB (loading dose of 500 mg at baseline and week 2, followed by 250 mg every 2 weeks [Q2W] thereafter) or PBO Q2W in combination with TCS for 16 weeks.

Main outcomes and measures: Efficacy analyses at week 16 included proportions of patients achieving Investigator's Global Assessment score of 0 or 1 (IGA [0,1]) with 2 or more points improvement from baseline, and 75% improvement in the Eczema Area and Severity Index (EASI-75). Key secondary end points included evaluation of itch, itch interference on sleep, and quality of life. Safety assessments included monitoring adverse events (AEs).

Results: The mean (SD) age of patients was 37.2 (19.3) years, 103 (48.8%) patients were women, 31 (14.7%) patients were Asian, and 28 (13.3%) patients were Black/African American. At week 16, IGA (0,1) was achieved by 145 (41.2%) patients in the LEB+TCS group vs 66 (22.1%) receiving PBO+TCS (P = .01); corresponding proportions of patients achieving EASI-75 were 69.5% vs 42.2% (P < .001). The LEB+TCS group showed statistically significant improvements in all key secondary end points. Most treatment-emergent adverse events (TEAEs) were nonserious, mild or moderate in severity, and did not lead to study discontinuation. The TEAEs frequently reported in the LEB+TCS group included conjunctivitis (7 [4.8%]), headache (7 [4.8%]), hypertension (4 [2.8%]), injection site reactions (4 [2.8%]), and herpes infection (5 [3.4%]) vs 1.5% or less patient-reported frequencies in the PBO+TCS group. Similar frequencies of patient-reported serious AEs following LEB+TCS (n = 2, 1.4%) and PBO+TCS (n = 1, 1.5%).

Conclusions and relevance: In this randomized phase 3 clinical trial, LEB+TCS was associated with improved outcomes in adolescents and adults with moderate-to-severe AD compared with TCS alone, and safety was consistent with previously reported AD trials.

Trial registration: ClinicalTrials.gov Identifier: NCT04250337.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Simpson reported personal fees from AbbVie, Amgen, Arena Pharmaceuticals, ASLAN, Benevolent AI Bio Limited (BAI), BiomX Ltd, Bluefin Biomedicine, Boehringer-Ingelheim, Boston Consulting Group, Collective Acumen, LLC (CA), Coronado, Dermira, Eli Lilly, Evidera, ExcerptaMedica, Galderma, GlaxoSmithKline, Forte Bio RX, Incyte Dermatologics, Janssen, Kyowa Kirin Pharmaceutical Development, Leo Pharm, Medscape LLC, Merck, Novaris, Ortho Galderma, Pfizer, Physicians World LLC, Pierre Fabre Dermo Cosmetique, Regeneron, Roivant, Sanofi-Genzyme, SPARC India, Trevi therapeutics, WebMD, and Valeant; grants from AbbVie, Amgen, Arcutis, ASLAN, Castle Biosciences, Celegene, CorEvitas, Dermavant, Dermira, Eli Lilly, Galderma, Incyte, Kymab, Kyowa Hakko Kirin, Leo Pharmaceuticals, Merck, Novartis, Pfizer, Regeneron, Sanofi, and TARGET-DERM outside the submitted work. Dr Gooderham reported grants, advisory roles, and speaker and/or personal fees from Eli Lilly, Amgen, Abbvie, Arcutis, AnaptysBIo, Aslan,Aristea, Boehringer, BMS, Dermira, Dermavant, Galderma, Incyte, Janssen, Kyowa Kirin, Leo Pharma, Medimmune, Merck, Meiji, Moonlake, Novartis, Pfizer, Regeneron, Sun Pharma, Sanofi Genzyme, UCB, and Bausch Health outside the submitted work. Dr Wollenberg reported personal fees from AbbVie, Almirall, Galderma, Janssen, Eli Lilly, Pfizer, Leo, Regeneron, and Sanofi outside the submitted work. Dr Weidinger reported personal fees from Pfizer, personal fees from LEO Pharma, Sanofi, Regeneron, Abbvie, Lilly, Kymab, grants from Sanofi, Pfizer, and grants from Leo Pharma during the conduct of the study. Dr Armstrong reported grants from Demira, Eli Lily , LEO, Kyowa Kirin, NovartisRegeneron, UCB, Galderma, Abbvie, Bristol Myer Squibb, and grants from Dermavant during the conduct of the study; personal fees from Abbvie, Bristol Myer Squibb, Dermavant, Eli Lilly, Janssen, LEO, Ortho Dermatologics, Regeneron, Sanofi, Sun Pharma, UCB, Boehringer, Parexel, Pfizer, Almirall, Arcutis, ASLAN, Beiersdorf,EPI, Incyte, Nimbus, Demira, Modernizing Medicine, and Novartis outside the submitted work. Dr Soung reported nonfinancial support from Eli Lilly (manuscuript preparation during the conduct of the study); grants from Abbvie, Pfizer, personal fees from Pfizer, Abbvie, Regneron, Sanofi, LEO, and grants from LEO, Sanofi, Kyowa Kirin, and Dermavant outside the submitted work. Dr Lima reported employment from Eli Lilly during the conduct of the study and outside the submitted work. Dr Witte reported employment from Eli Lilly during the conduct of the study and outside the submitted work. Dr Xu reported salaried employment and stock holdings in Eli Lilly outside the submitted work. Dr ElMaraghy reported employment and stock holdings in Eli outside the submitted work. Dr Natalie reported personal fees, employment and stockholdings from Eli Lilly during the conduct of the study. Dr Pierce reported employment and stockholdings from Eli Lilly during the conduct of the study and outside the submitted work. Dr Blauvelt reported serving as a speaker/receiving honoraria from AbbVie, Bristol-Myers Squibb, Eli Lilly, Regeneron, and UCB, serving as a scientific adviser/receiving honoraria from AbbVie, Abcentra, Affibody, Aligos, Almirall, Alumis, Amgen, Anaptysbio, Arcutis, Arena, Aslan, Athenex, Bluefin Biomedicine, Boehringer Ingelheim, Bristol-Myers Squibb, Cara Therapeutics, Dermavant, EcoR1, Eli Lilly, Escient, Evelo, Evommune, Forte, Galderma, HighlightII Pharma, Incyte, Janssen, Landos, Leo, Merck, Novartis, Pfizer, Rapt, Regeneron, Sanofi Genzyme, Spherix Global Insights, Sun Pharma, TLL Pharmaceutical, TrialSpark, UCB Pharma, Vibliome, and Xencor, and has acted as a clinical study investigator/institution receiving clinical study funds from AbbVie, Acelyrin, Amgen, Arcutis, Athenex, Boehringer Ingelheim, Bristol-Myers Squibb, Concert, Dermavant, Eli Lilly and Company, Evelo, Galderma, Incyte, Janssen, Leo, Merck, Novartis, Pfizer, Regeneron, Sun Pharma, and UCB Pharma. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. CONSORT Diagram for Patient Disposition
CONSORT indicates Consolidated Standards of Reporting Trials; ITT, intent-to-treat; LEB, lebrikizumab; mITT, modified intent-to-treat; Q2W, every 2 weeks; TCS, topical corticosteroid.
Figure 2.
Figure 2.. Time-Course Response for the Clinical Outcomes (Primary and Secondary End Points)
Missing data due to lack of efficacy or data after rescue medication usage were imputed with net reclassification index (for categorical end points) or baseline values (for continuous end points). Other missing data were imputed with multiple imputation. DLQI indicates Dermatology Life Quality Index; EASI, Eczema Area and Severity Index; IGA, Investigator's Global Assessment; LEB, lebrikizumab; mITT, modified intent-to-treat; NRS, numeric rating scale; PBO, placebo; TCS, topical corticosteroids. aP < .001. bPatients with baseline Pruritus NRS score of 4 or greater. cPatients with baseline DLQI of 4 or greater.
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