Pooled safety analysis of baricitinib in adult patients with atopic dermatitis from 8 randomized clinical trials.
Journal
Journal of the European Academy of Dermatology and Venereology : JEADV
ISSN: 1468-3083
Titre abrégé: J Eur Acad Dermatol Venereol
Pays: England
ID NLM: 9216037
Informations de publication
Date de publication:
Feb 2021
Feb 2021
Historique:
received:
10
08
2020
accepted:
07
09
2020
pubmed:
15
9
2020
medline:
15
5
2021
entrez:
14
9
2020
Statut:
ppublish
Résumé
Janus kinase (JAK) inhibition is a new mode of action in atopic dermatitis (AD); clarity about drug class safety considerations in the context of AD is important. Baricitinib, an oral, reversible, selective inhibitor of JAK1/JAK2, is in late-stage development for adult patients with moderate-to-severe AD. To report pooled safety data for baricitinib in patients with moderate-to-severe AD in the clinical development program including long-term extension (LTE) studies. This analysis included patient-level safety data from six double-blinded, randomized, placebo-controlled studies (one phase 2 and five phase 3), one double-blinded, randomized, LTE study and one open-label LTE study, reported in three data sets: placebo-controlled, 2-mg - 4-mg extended and All-bari AD. Safety outcomes include treatment-emergent adverse events, adverse events of special interest and abnormal laboratory changes. Proportions of patients with events and incidence rates were calculated. Data were collected for 2531 patients who were given baricitinib for 2247 patient-years (median duration 310 days). The frequency of serious infections, opportunistic infections and conjunctival disorders was low and similar between treatment groups in the placebo-controlled period. The most common serious infections were eczema herpeticum [n = 11, incidence rates (IR) = 0.5], cellulitis (n = 6, IR = 0.3) and pneumonia (n = 3, IR = 0.1). There were four opportunistic infections (IR = 0.2). No malignancies, gastrointestinal perforations, positively adjudicated cardiovascular events or tuberculosis were reported in the placebo-controlled period in baricitinib-treated patients. Frequency of herpes simplex was higher in the 4-mg group (6.1%) vs. the 2-mg (3.6%) and placebo group (2.7%); IRs in the extended data set (2-mg IR = 9.6; 4-mg IR = 14.5) were lower vs. the placebo-controlled data set (2-mg IR = 12.4; 4-mg IR = 21.3). In the All-bari AD data set, there were two positively adjudicated major adverse cardiovascular events (2-mg group): two venous thrombosis events (4-mg group) and one death. This integrated safety analysis in patients with moderate-to-severe AD confirms the established safety profile of baricitinib.
Sections du résumé
BACKGROUND
BACKGROUND
Janus kinase (JAK) inhibition is a new mode of action in atopic dermatitis (AD); clarity about drug class safety considerations in the context of AD is important. Baricitinib, an oral, reversible, selective inhibitor of JAK1/JAK2, is in late-stage development for adult patients with moderate-to-severe AD.
OBJECTIVE
OBJECTIVE
To report pooled safety data for baricitinib in patients with moderate-to-severe AD in the clinical development program including long-term extension (LTE) studies.
METHODS
METHODS
This analysis included patient-level safety data from six double-blinded, randomized, placebo-controlled studies (one phase 2 and five phase 3), one double-blinded, randomized, LTE study and one open-label LTE study, reported in three data sets: placebo-controlled, 2-mg - 4-mg extended and All-bari AD. Safety outcomes include treatment-emergent adverse events, adverse events of special interest and abnormal laboratory changes. Proportions of patients with events and incidence rates were calculated.
RESULTS
RESULTS
Data were collected for 2531 patients who were given baricitinib for 2247 patient-years (median duration 310 days). The frequency of serious infections, opportunistic infections and conjunctival disorders was low and similar between treatment groups in the placebo-controlled period. The most common serious infections were eczema herpeticum [n = 11, incidence rates (IR) = 0.5], cellulitis (n = 6, IR = 0.3) and pneumonia (n = 3, IR = 0.1). There were four opportunistic infections (IR = 0.2). No malignancies, gastrointestinal perforations, positively adjudicated cardiovascular events or tuberculosis were reported in the placebo-controlled period in baricitinib-treated patients. Frequency of herpes simplex was higher in the 4-mg group (6.1%) vs. the 2-mg (3.6%) and placebo group (2.7%); IRs in the extended data set (2-mg IR = 9.6; 4-mg IR = 14.5) were lower vs. the placebo-controlled data set (2-mg IR = 12.4; 4-mg IR = 21.3). In the All-bari AD data set, there were two positively adjudicated major adverse cardiovascular events (2-mg group): two venous thrombosis events (4-mg group) and one death.
CONCLUSION
CONCLUSIONS
This integrated safety analysis in patients with moderate-to-severe AD confirms the established safety profile of baricitinib.
Substances chimiques
Azetidines
0
Pharmaceutical Preparations
0
Purines
0
Pyrazoles
0
Sulfonamides
0
baricitinib
ISP4442I3Y
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
476-485Subventions
Organisme : Incyte
Organisme : Eli Lilly and Company
Informations de copyright
© 2020 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.
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