Efficacy and safety of fezakinumab (an IL-22 monoclonal antibody) in adults with moderate-to-severe atopic dermatitis inadequately controlled by conventional treatments: A randomized, double-blind, phase 2a trial.
- Guttman-Yassky E Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York; Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York. Electronic address: Emma.Guttman@mountsinai.org.
- Brunner PM Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York.
- Neumann AU Institute of Environmental Medicine, University Center for Health Sciences at the Klinikum Augsburg, Technical University Munich and Helmholtz Zentrum München - German Research Center for Environmental Health, Augsburg, Germany; Swiss Institute of Allergy and Asthma Research, University of Zürich, Davos, Switzerland; Berlin-Brandenburg Center for Regenerative Therapies, Charité University Hospital Berlin, Berlin, Germany.
- Khattri S Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York.
- Pavel AB Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York.
- Malik K Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York.
- Singer GK Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York.
- Baum D Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York.
- Gilleaudeau P Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York.
- Sullivan-Whalen M Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York.
- Rose S Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York.
- Jim On S Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York.
- Li X Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York.
- Fuentes-Duculan J Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York.
- Estrada Y Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York.
- Garcet S Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York.
- Traidl-Hoffmann C Institute of Environmental Medicine, University Center for Health Sciences at the Klinikum Augsburg, Technical University Munich and Helmholtz Zentrum München - German Research Center for Environmental Health, Augsburg, Germany; Christine Kühne - Center for Allergy Research and Education, Davos, Switzerland.
- Krueger JG Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York.
- Lebwohl MG Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York.
- 2018-01-22
Published in:
- Journal of the American Academy of Dermatology. - 2018
IL-22
atopic dermatitis
fezakinumab
moderate-to-severe AD
placebo-controlled trial
Adult
Antibodies, Monoclonal
Antibodies, Monoclonal, Humanized
Dermatitis, Atopic
Dose-Response Relationship, Drug
Double-Blind Method
Drug Administration Schedule
Female
Follow-Up Studies
Humans
Infusions, Intravenous
Interleukins
Male
Middle Aged
Severity of Illness Index
Treatment Outcome
English
BACKGROUND
Interleukin 22 promotes epidermal hyperplasia and inhibits skin barrier function.
OBJECTIVE
Evaluate interleukin 22 blockade in adults with moderate-to-severe atopic dermatitis (AD).
METHODS
We performed a randomized, double-blind, placebo-controlled trial with intravenous fezakinumab monotherapy every 2 weeks for 10 weeks, with follow-up assessments until 20 weeks. The change in SCOring AD (SCORAD) score from baseline at 12 weeks served as the primary end point.
RESULTS
At 12 weeks, the mean declines in SCORAD for the entire study population were 13.8 ± 2.7 in the fezakinumab arm and 8.0 ± 3.1 in the placebo arm (P = .134). In the severe AD patient subset (with a baseline SCORAD of ≥50), SCORAD decline was significantly stronger in the drug-treated patients than placebo-treated patients at 12 weeks (21.6 ± 3.8 vs 9.6 ± 4.2, P = .029) and 20 weeks (27.4 ± 3.9 vs 11.5 ± 5.1, P = .010). At 12 weeks, improvements in body surface area involvement in the entire population were significantly stronger in the drug-treated than placebo-treated patients (12.4% ± 2.4 vs 6.2% ± 2.7; P = .009), and in the severe AD subset, the decline in Investigator Global Assessment was significantly higher in the drug-treated than placebo-treated patients (0.7 ± 0.2 vs 0.3 ± 0.1; P = .034). All scores showed progressive improvements after last dosing (10 weeks) until end of study (20 weeks). Common adverse events were upper respiratory tract infections.
LIMITATIONS
The limited sample size and lack of assessment with Eczema Area and Severity Index and a pruritus numerical rating scale were limiting factors. Significance was primarily obtained in severe AD.
CONCLUSION
Fezakinumab was well-tolerated, with sustained clinical improvements after last drug dosing.
Interleukin 22 promotes epidermal hyperplasia and inhibits skin barrier function.
OBJECTIVE
Evaluate interleukin 22 blockade in adults with moderate-to-severe atopic dermatitis (AD).
METHODS
We performed a randomized, double-blind, placebo-controlled trial with intravenous fezakinumab monotherapy every 2 weeks for 10 weeks, with follow-up assessments until 20 weeks. The change in SCOring AD (SCORAD) score from baseline at 12 weeks served as the primary end point.
RESULTS
At 12 weeks, the mean declines in SCORAD for the entire study population were 13.8 ± 2.7 in the fezakinumab arm and 8.0 ± 3.1 in the placebo arm (P = .134). In the severe AD patient subset (with a baseline SCORAD of ≥50), SCORAD decline was significantly stronger in the drug-treated patients than placebo-treated patients at 12 weeks (21.6 ± 3.8 vs 9.6 ± 4.2, P = .029) and 20 weeks (27.4 ± 3.9 vs 11.5 ± 5.1, P = .010). At 12 weeks, improvements in body surface area involvement in the entire population were significantly stronger in the drug-treated than placebo-treated patients (12.4% ± 2.4 vs 6.2% ± 2.7; P = .009), and in the severe AD subset, the decline in Investigator Global Assessment was significantly higher in the drug-treated than placebo-treated patients (0.7 ± 0.2 vs 0.3 ± 0.1; P = .034). All scores showed progressive improvements after last dosing (10 weeks) until end of study (20 weeks). Common adverse events were upper respiratory tract infections.
LIMITATIONS
The limited sample size and lack of assessment with Eczema Area and Severity Index and a pruritus numerical rating scale were limiting factors. Significance was primarily obtained in severe AD.
CONCLUSION
Fezakinumab was well-tolerated, with sustained clinical improvements after last drug dosing.
- Language
-
- English
- Open access status
- hybrid
- Identifiers
-
- DOI 10.1016/j.jaad.2018.01.016
- PMID 29353025
- Persistent URL
- https://sonar.ch/global/documents/191296
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