PMID- 36082590
OWN - NLM
STAT- MEDLINE
DCOM- 20221206
LR  - 20230415
IS  - 1365-2133 (Electronic)
IS  - 0007-0963 (Print)
IS  - 0007-0963 (Linking)
VI  - 187
IP  - 6
DP  - 2022 Dec
TI  - Safety of tralokinumab in adult patients with moderate-to-severe atopic 
      dermatitis: pooled analysis of five randomized, double-blind, placebo-controlled 
      phase II and phase III trials.
PG  - 888-899
LID - 10.1111/bjd.21867 [doi]
AB  - BACKGROUND: Tralokinumab is a fully human monoclonal antibody that neutralizes 
      the activity of interleukin-13, a key pathogenic driver of atopic dermatitis 
      (AD). Clinical trials including adults with moderate-to-severe AD, of up to 
      52 weeks' duration, showed tralokinumab was efficacious and well tolerated. 
      OBJECTIVES: To characterize the safety profile of tralokinumab for the treatment 
      of moderate-to-severe AD. METHODS: Safety and laboratory measures were assessed 
      in pooled analyses of phase II and III placebo-controlled clinical trials of 
      tralokinumab in moderate-to-severe AD (NCT02347176, NCT03562377, NCT03131648, 
      NCT03160885, NCT03363854). RESULTS: In total, 2285 patients were randomized in 
      the initial treatment periods up to 16 weeks (1605 tralokinumab, 680 placebo). 
      The frequencies of any adverse event (AE) were 65.7% for tralokinumab and 67.2% 
      for placebo. The respective rates were 640 and 678 events per 100 patient-years 
      of exposure (ep100PYE); rate ratio 1.0, 95% confidence interval (CI) 0.9-1.1. 
      Serious AEs occurred in 2.1% of patients with tralokinumab and 2.8% with placebo 
      (7.4 and 11.9 ep100PYE; rate ratio 0.7, 95% CI 0.4-1.2). The most common AEs 
      occurring at a higher frequency and rate with tralokinumab vs. placebo were: 
      viral upper respiratory tract infection (15.7% vs. 12.2%; 65.1 vs. 53.5 
      ep100PYE); upper respiratory tract infection (5.6% vs. 4.8%; 20.8 vs. 18.5 
      ep100PYE); conjunctivitis (5.4% vs. 1.9%; 21.0 vs. 6.9 ep100PYE); and 
      injection-site reaction (3.5% vs. 0.3%; 22.9 vs. 4.0 ep100PYE). Some events in 
      safety areas of interest occurred at a lower frequency and rate with tralokinumab 
      vs. placebo: skin infections requiring systemic treatment (2.6% vs. 5.5%; 9.7 vs. 
      22.8 ep100PYE), eczema herpeticum (0.3% vs. 1.5%; 1.2 vs. 5.2 ep100PYE), 
      opportunistic infections (3.4% vs. 4.9%; 13.0 vs. 21.3 ep100PYE) and serious 
      infections (0.4% vs. 1.1%; 1.3 vs. 3.7 ep100PYE). AEs did not increase with 
      continued maintenance and open-label treatment, including rates of common or 
      serious AEs and AEs leading to study drug discontinuation. No clinically 
      meaningful changes in mean laboratory measures were observed with treatment up to 
      1 year. CONCLUSIONS: Across the AD population pool from five clinical trials, 
      tralokinumab was well tolerated, with consistent safety findings during treatment 
      of patients with moderate-to-severe AD. The safety profile during prolonged 
      tralokinumab treatment was consistent with that during the initial treatment 
      period; the frequency of events did not increase over time. What is already known 
      about this topic? Tralokinumab is a fully human monoclonal antibody that 
      specifically neutralizes interleukin-13, a key cytokine driving skin inflammation 
      and epidermal barrier dysfunction in atopic dermatitis (AD). In clinical trials 
      in moderate-to-severe AD, tralokinumab provided significant and early 
      improvements in the extent and severity of AD and was well tolerated, with an 
      overall safety profile comparable with placebo over 52 weeks. What does this 
      study add? We report the frequency and rate of adverse events (AEs) from pooled 
      observations of over 2000 patients from five phase II and phase III 
      placebo-controlled clinical trials of tralokinumab in moderate-to-severe AD. 
      During initial treatment up to 16 weeks, the frequencies of any AE and of serious 
      AEs were similar for tralokinumab and placebo. AE rates did not increase with 
      continued treatment up to 52 weeks. Common AEs occurring more frequently with 
      tralokinumab vs. placebo were viral and upper respiratory tract infection, 
      conjunctivitis and injection-site reaction. Some events occurred at a lower 
      frequency and rate with tralokinumab vs. placebo, such as skin infections 
      requiring systemic treatment, eczema herpeticum and opportunistic and serious 
      infections. No clinically meaningful changes in mean laboratory measures were 
      observed.
CI  - (c) 2022 The Authors. British Journal of Dermatology published by John Wiley & Sons 
      Ltd on behalf of British Association of Dermatologists.
FAU - Simpson, Eric L
AU  - Simpson EL
AD  - Department of Dermatology, Oregon Health & Science University, Portland, OR, USA.
FAU - Merola, Joseph F
AU  - Merola JF
AUID- ORCID: 0000-0001-6514-4353
AD  - Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
FAU - Silverberg, Jonathan I
AU  - Silverberg JI
AUID- ORCID: 0000-0003-3686-7805
AD  - Department of Dermatology, The George Washington University School of Medicine 
      and Health Sciences, Washington, DC, USA.
FAU - Reich, Kristian
AU  - Reich K
AUID- ORCID: 0000-0001-5248-4332
AD  - Translational Research in Inflammatory Skin Diseases, Institute for Health 
      Services Research in Dermatology and Nursing, University Medical Center 
      Hamburg-Eppendorf, Hamburg, Germany.
FAU - Warren, Richard B
AU  - Warren RB
AD  - Dermatology Centre, Salford Royal NHS Foundation Trust, and NIHR Biomedical 
      Research Centre, The University of Manchester, Manchester, UK.
FAU - Staumont-Salle, Delphine
AU  - Staumont-Salle D
AD  - Dermatology Service, Lille University Hospital, Inserm U1286 INFINITE (Institute 
      for Translational Research in Inflammation), Lille University, Lille, France.
FAU - Girolomoni, Giampiero
AU  - Girolomoni G
AD  - Section of Dermatology, Department of Medicine, University of Verona, Verona, 
      Italy.
FAU - Papp, Kim
AU  - Papp K
AUID- ORCID: 0000-0001-9557-3642
AD  - Probity Medical Research and K Papp Clinical Research, Waterloo, ON, Canada.
FAU - de Bruin-Weller, Marjolein
AU  - de Bruin-Weller M
AUID- ORCID: 0000-0002-1249-6993
AD  - National Expertise Center for Atopic Dermatitis, Department of 
      Dermatology/Allergology, University Medical Center Utrecht, Utrecht, the 
      Netherlands.
FAU - Thyssen, Jacob P
AU  - Thyssen JP
AD  - Department of Dermatology and Venereology, Bispebjerg Hospital, University of 
      Copenhagen, Copenhagen, Denmark.
FAU - Zachariae, Rebecca
AU  - Zachariae R
AD  - LEO Pharma A/S, Ballerup, Denmark.
FAU - Olsen, Christiana K
AU  - Olsen CK
AD  - LEO Pharma A/S, Ballerup, Denmark.
FAU - Wollenberg, Andreas
AU  - Wollenberg A
AUID- ORCID: 0000-0003-0177-8722
AD  - Klinikum der Universitat Munchen, Klinik und Poliklinik fur Dermatologie und 
      Allergologie, Munich, Germany.
LA  - eng
GR  - LEO Pharma/
GR  - MedImmune LLC/
PT  - Clinical Trial, Phase II
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20221026
PL  - England
TA  - Br J Dermatol
JT  - The British journal of dermatology
JID - 0004041
RN  - GK1LYB375A (tralokinumab)
RN  - 0 (Interleukin-13)
RN  - 0 (Antibodies, Monoclonal)
SB  - IM
MH  - Adult
MH  - Humans
MH  - *Dermatitis, Atopic/drug therapy/pathology
MH  - Interleukin-13
MH  - *Kaposi Varicelliform Eruption
MH  - Treatment Outcome
MH  - Antibodies, Monoclonal
MH  - Double-Blind Method
MH  - *Conjunctivitis/chemically induced
MH  - Injection Site Reaction
MH  - *Skin Diseases, Infectious
MH  - *Respiratory Tract Infections
MH  - Severity of Illness Index
PMC - PMC10091996
COIS- E.L.S. reports grants from Galderma, Merck, Novartis, Tioga and Vanda; personal 
      fees from Arena Pharmaceuticals, BenevolentAI, BiomX, Bluefin Biomedicine, 
      Boehringer Ingelheim, Boston Consulting Group, California Pharmaceuticals, 
      Collective Acumen, Coronado Biosciences, Dermira, Evidera, Excerpta Medica, Forte 
      Bio, Janssen, Medscape, Ortho Dermatologics, Sanofi Genzyme and SPARC India; and 
      grants and personal fees from AbbVie, Celgene/Amgen, Lilly, Incyte, Kyowa Kirin, 
      LEO Pharma, Pfizer, Regeneron and Sanofi. J.F.M. is a consultant and/or 
      investigator for AbbVie, Arena, Avotres, Biogen, Bristol Myers Squibb, Celgene, 
      Dermavant, Lilly, EMD Serono, Janssen, LEO Pharma, Merck, Novartis, Pfizer, 
      Regeneron, Sanofi, Sun and UCB. J.I.S. reports personal fees from AbbVie, 
      AnaptysBio, Arena, Asana, Bluefin Biomedicine, Boehringer Ingelheim, Celgene, 
      Dermavant, Dermira, DS Biopharma, Kiniksa, LEO Pharma, Lilly, Luna, Menlo, 
      Novartis, Pfizer, Realm, Regeneron and Sanofi Genzyme; and grants and personal 
      fees from Galderma and GlaxoSmithKline outside the submitted work. K.R. has 
      served as an advisor and/or paid speaker for and/or participated in clinical 
      trials sponsored by AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers 
      Squibb, Celgene, Forward Pharma, Gilead, Galderma, Janssen-Cilag, Kyowa Kirin, 
      LEO Pharma, Lilly, Medac, Novartis, Ocean Pharma, Pfizer, Sanofi and UCB; and is 
      cofounder of Moonlake Immunotherapeutics. R.B.W. has received research grants or 
      consulting fees from AbbVie, Almirall, Amgen, Arena, Astellas, Avillion, 
      Boehringer Ingelheim, Bristol Myers Squibb, Celgene, DiCE, Lilly, GSK, Janssen, 
      LEO Pharma, Medac, Novartis, Pfizer, Sanofi, Sun Pharma, UCB and UNION. D.S-S. 
      has been a speaker, consultant and/or investigator for AbbVie, Almirall, Amgen, 
      AstraZeneca, Boehringer Ingelheim, Celgene, Eli Lilly, Galderma, Janssen, LEO 
      Pharma, Novartis, Pfizer, Sanofi Genzyme and UCB. G.G. has received personal fees 
      from AbbVie, Abiogen, Almirall, Amgen, Biogen, Boehringer Ingelheim, Bristol 
      Myers Squibb, Celgene, Celltrion, Fresenius Kabi, Galderma, Genzyme, Insiderma, 
      LEO Pharma, Lilly, Menlo, Novartis, OM Pharma, Pfizer, Regeneron, Samsung, Sandoz 
      and UCB. K.P. is an investigator, consultant, speaker or scientific officer for 
      or has served on steering committees or advisory boards for AbbVie, Akros, Amgen, 
      Anacor, Arcutis, Astellas, Avillion, Bausch Health/Valeant, Baxalta, Boehringer 
      Ingelheim, Bristol Myers Squibb, Can-Fite BioPharma, Celgene, Coherus, Dermavant, 
      Dermira, DiCE, Dow Pharmaceuticals, Evelo, Galapagos, Galderma, Gilead, GSK, 
      Incyte, Janssen, Kyowa Kirin, LEO Pharma, Lilly, MedImmune, Meiji Seika Pharma, 
      Merck (MSD), Merck-Serono, Mitsubishi Pharma, Moberg Pharma, Novartis, Pfizer, 
      PRCL Research, Regeneron, Roche, Sanofi-Aventis/Genzyme, Sun Pharma, Takeda, UCB 
      and Xencor. M.dB-W. has been a consultant, advisory board member and/or speaker 
      for AbbVie, Almirall, Arena, Lilly, Galderma, Janssen, LEO Pharma, Pfizer, 
      Regeneron and Sanofi Genzyme. J.P.T. reports speaker honoraria from AbbVie, 
      Almirall, LEO Pharma, Regeneron, and Sanofi Genzyme and research grants from 
      Regeneron and Sanofi Genzyme and has attended advisory boards for AbbVie, LEO 
      Pharma, Lilly, Pfizer, Regeneron and Sanofi Genzyme. R.Z. and C.K.O. are 
      employees of LEO Pharma A/S. A.W. reports honoraria for conduct of the ECZTRA 1 
      and ECZTRA 2 trials to Ludwig Maximilian University of Munich from LEO Pharma A/S 
      during the conduct of the study; personal fees from AbbVie, Chugai, Galderma, LEO 
      Pharma, Lilly, MedImmune, Novartis, Pfizer, Regeneron and Sanofi-Aventis; and 
      grants from LEO Pharma outside the submitted work.
EDAT- 2022/09/10 06:00
MHDA- 2022/12/07 06:00
PMCR- 2023/04/12
CRDT- 2022/09/09 04:13
PHST- 2022/08/26 00:00 [revised]
PHST- 2021/11/19 00:00 [received]
PHST- 2022/09/03 00:00 [accepted]
PHST- 2022/09/10 06:00 [pubmed]
PHST- 2022/12/07 06:00 [medline]
PHST- 2022/09/09 04:13 [entrez]
PHST- 2023/04/12 00:00 [pmc-release]
AID - BJD21867 [pii]
AID - 10.1111/bjd.21867 [doi]
PST - ppublish
SO  - Br J Dermatol. 2022 Dec;187(6):888-899. doi: 10.1111/bjd.21867. Epub 2022 Oct 26.