PMID- 36630140 OWN - NLM STAT- MEDLINE DCOM- 20230217 LR - 20230719 IS - 2168-6084 (Electronic) IS - 2168-6068 (Print) IS - 2168-6068 (Linking) VI - 159 IP - 2 DP - 2023 Feb 1 TI - 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). PG - 182-191 LID - 10.1001/jamadermatol.2022.5534 [doi] AB - 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. FAU - Simpson, Eric L AU - Simpson EL AD - Department of Dermatology, Oregon Health & Science University, Portland. FAU - Gooderham, Melinda AU - Gooderham M AD - Skin for Dermatology, Peterborough, Ontario, Canada. FAU - Wollenberg, Andreas AU - Wollenberg A AD - LMU - Department of Dermatology and Allergology, Munich, Germany. AD - Department of Dermatology, Free University Brussels, University Hospital Brussels, Brussels, Belgium. FAU - Weidinger, Stephan AU - Weidinger S AD - Department of Dermatology, Christian Albrechts University of Kiel, Kiel, Germany. FAU - Armstrong, April AU - Armstrong A AD - Keck School of Medicine of the USC, Los Angeles, California. FAU - Soung, Jennifer AU - Soung J AD - Southern California Dermatology, Inc, Santa Ana. FAU - Ferrucci, Silvia AU - Ferrucci S AD - Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Dermatology Unit, Milan, Italy. FAU - Lima, Renata Gontijo AU - Lima RG AD - Eli Lilly and Company, Indianapolis, Indiana. FAU - Witte, Michael M AU - Witte MM AD - Eli Lilly and Company, Indianapolis, Indiana. FAU - Xu, Wen AU - Xu W AD - Eli Lilly and Company, Indianapolis, Indiana. FAU - ElMaraghy, Hany AU - ElMaraghy H AD - Eli Lilly and Company, Indianapolis, Indiana. FAU - Natalie, Chitra R AU - Natalie CR AD - Eli Lilly and Company, Indianapolis, Indiana. FAU - Pierce, Evangeline AU - Pierce E AD - Eli Lilly and Company, Indianapolis, Indiana. FAU - Blauvelt, Andrew AU - Blauvelt A AD - Oregon Medical Research Center, Portland. CN - ADhere Investigators LA - eng SI - ClinicalTrials.gov/NCT04250337 PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - United States TA - JAMA Dermatol JT - JAMA dermatology JID - 101589530 RN - 0 (Adrenal Cortex Hormones) RN - 0 (Antibodies, Monoclonal) RN - 0 (Dermatologic Agents) RN - 0 (Immunoglobulin A) RN - 0 (Interleukin-13) RN - U9JLP7V031 (lebrikizumab) SB - IM EIN - JAMA Dermatol. 2023 Sep 1;159(9):1014. PMID: 37466974 MH - Adolescent MH - Adult MH - Female MH - Humans MH - Male MH - *Adrenal Cortex Hormones/therapeutic use MH - Antibodies, Monoclonal MH - *Dermatitis, Atopic/drug therapy MH - *Dermatologic Agents/therapeutic use MH - Double-Blind Method MH - Immunoglobulin A MH - Interleukin-13 MH - Quality of Life MH - Severity of Illness Index MH - Treatment Outcome PMC - PMC9857439 COIS- 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. FIR - Jarell, Abel IR - Jarell A FIR - Sadick, Neil IR - Sadick N FIR - Sofen, Howard IR - Sofen H FIR - Wallace, Paul W IR - Wallace PW FIR - Carpio, Jose M IR - Carpio JM FIR - Greenstein, David IR - Greenstein D FIR - Moore, Angela IR - Moore A FIR - Mendez, Jose M IR - Mendez JM FIR - Guenthner, Scott T IR - Guenthner ST FIR - McFalda, Wendy L IR - McFalda WL FIR - Laquer, Vivian T IR - Laquer VT FIR - Forman, Seth IR - Forman S FIR - Schlesinger, Todd IR - Schlesinger T FIR - Blauvelt, Andrew IR - Blauvelt A FIR - Crowley, Jeffrey J IR - Crowley JJ FIR - Tan, Ricardo IR - Tan R FIR - Averill, Francis J IR - Averill FJ FIR - George, Rosalyn E IR - George RE FIR - Armas, Eddie IR - Armas E FIR - Lockshin, Benjamin IR - Lockshin B FIR - Soung, Jennifer IR - Soung J FIR - Nahm, Walter K IR - Nahm WK FIR - Ehrlich, Alison A IR - Ehrlich AA FIR - Dhawan, Sunil S IR - Dhawan SS FIR - Simpson, Eric L IR - Simpson EL FIR - Sitar, Steve IR - Sitar S FIR - Bagel, Jerry IR - Bagel J FIR - Rich, Phoebe IR - Rich P FIR - Torkan, Bruce IR - Torkan B FIR - Fivenson, David F IR - Fivenson DF FIR - Weisman, Jamie D IR - Weisman JD FIR - Stone, Melody L IR - Stone ML FIR - Armstrong, April IR - Armstrong A FIR - Saifi, Mirwais IR - Saifi M FIR - Glick, Brad P IR - Glick BP FIR - Gooderham, Melinda IR - Gooderham M FIR - Day, Isaiah IR - Day I FIR - Albrecht, Lorne IR - Albrecht L FIR - Wiseman, Marni IR - Wiseman M FIR - Gratton, David IR - Gratton D FIR - Hong, Chi-Ho IR - Hong CH FIR - Majorek-Olechowska, Bernadetta IR - Majorek-Olechowska B FIR - Reich, Adam IR - Reich A FIR - Krecisz, Beata IR - Krecisz B FIR - Walecka-Herniczek, Irena IR - Walecka-Herniczek I FIR - Weglowska, Jolanta IR - Weglowska J FIR - Bergler-Czop, Beata IR - Bergler-Czop B FIR - Cimoszko, Boguslawa IR - Cimoszko B FIR - Padlewska, Kamila IR - Padlewska K FIR - Czubek, Maria IR - Czubek M FIR - Pinter, Andreas IR - Pinter A FIR - Reich, Kristian IR - Reich K FIR - Wildfeuer, Thomas IR - Wildfeuer T FIR - Aschoff, Roland IR - Aschoff R EDAT- 2023/01/12 06:00 MHDA- 2023/02/18 06:00 PMCR- 2023/01/11 CRDT- 2023/01/11 11:33 PHST- 2023/01/12 06:00 [pubmed] PHST- 2023/02/18 06:00 [medline] PHST- 2023/01/11 11:33 [entrez] PHST- 2023/01/11 00:00 [pmc-release] AID - 2800236 [pii] AID - doi220065 [pii] AID - 10.1001/jamadermatol.2022.5534 [doi] PST - ppublish SO - JAMA Dermatol. 2023 Feb 1;159(2):182-191. doi: 10.1001/jamadermatol.2022.5534.