Tags

Type your tag names separated by a space and hit enter

Pooled safety analysis of baricitinib in adult patients with atopic dermatitis from 8 randomized clinical trials.
J Eur Acad Dermatol Venereol. 2021 Feb; 35(2):476-485.JE

Abstract

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

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

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

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

This integrated safety analysis in patients with moderate-to-severe AD confirms the established safety profile of baricitinib.

Authors+Show Affiliations

University Hospital of Bonn, Bonn, Germany.Department of Dermatology and Allergy, Herlev-Gentofte Hospital University of Copenhagen, Copenhagen, Denmark.University Med Cen Hamburg-Eppendorf, Hamburg, Germany.Oregon Health & Science University, Portland, OR, USA.Department of Dermatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.Department of Dermatology, Hospital Infantil Universitario Niño Jesús, Madrid, Spain.UMC Utrecht, Utrecht, the Netherlands.Comprehensive Center for Inflammation Medicine, University Hospital Schleswig Holstein, Luebeck, Germany.Innovaderm Research, Montreal, QC, Canada.SKiN Centre for Dermatology, Peterborough, ON, Canada.Medical Dermatology Specialists, Atlanta, GA, USA.Eli Lilly and Company, Indianapolis, IN, USA.Eli Lilly and Company, Indianapolis, IN, USA.Eli Lilly and Company, Indianapolis, IN, USA.Eli Lilly and Company, Indianapolis, IN, USA.Eli Lilly and Company, Indianapolis, IN, USA.Eli Lilly and Company, Indianapolis, IN, USA.Eli Lilly and Company, Indianapolis, IN, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32926462

Citation

Bieber, T, et al. "Pooled Safety Analysis of Baricitinib in Adult Patients With Atopic Dermatitis From 8 Randomized Clinical Trials." Journal of the European Academy of Dermatology and Venereology : JEADV, vol. 35, no. 2, 2021, pp. 476-485.
Bieber T, Thyssen JP, Reich K, et al. Pooled safety analysis of baricitinib in adult patients with atopic dermatitis from 8 randomized clinical trials. J Eur Acad Dermatol Venereol. 2021;35(2):476-485.
Bieber, T., Thyssen, J. P., Reich, K., Simpson, E. L., Katoh, N., Torrelo, A., De Bruin-Weller, M., Thaci, D., Bissonnette, R., Gooderham, M., Weisman, J., Nunes, F., Brinker, D., Issa, M., Holzwarth, K., Gamalo, M., Riedl, E., & Janes, J. (2021). Pooled safety analysis of baricitinib in adult patients with atopic dermatitis from 8 randomized clinical trials. Journal of the European Academy of Dermatology and Venereology : JEADV, 35(2), 476-485. https://doi.org/10.1111/jdv.16948
Bieber T, et al. Pooled Safety Analysis of Baricitinib in Adult Patients With Atopic Dermatitis From 8 Randomized Clinical Trials. J Eur Acad Dermatol Venereol. 2021;35(2):476-485. PubMed PMID: 32926462.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pooled safety analysis of baricitinib in adult patients with atopic dermatitis from 8 randomized clinical trials. AU - Bieber,T, AU - Thyssen,J P, AU - Reich,K, AU - Simpson,E L, AU - Katoh,N, AU - Torrelo,A, AU - De Bruin-Weller,M, AU - Thaci,D, AU - Bissonnette,R, AU - Gooderham,M, AU - Weisman,J, AU - Nunes,F, AU - Brinker,D, AU - Issa,M, AU - Holzwarth,K, AU - Gamalo,M, AU - Riedl,E, AU - Janes,J, Y1 - 2020/10/06/ PY - 2020/08/10/received PY - 2020/09/07/accepted PY - 2020/9/15/pubmed PY - 2021/5/15/medline PY - 2020/9/14/entrez SP - 476 EP - 485 JF - Journal of the European Academy of Dermatology and Venereology : JEADV JO - J Eur Acad Dermatol Venereol VL - 35 IS - 2 N2 - 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: 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: 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: 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: This integrated safety analysis in patients with moderate-to-severe AD confirms the established safety profile of baricitinib. SN - 1468-3083 UR - https://www.unboundmedicine.com/medline/citation/32926462/Pooled_safety_analysis_of_baricitinib_in_adult_patients_with_atopic_dermatitis_from_8_randomized_clinical_trials_ L2 - https://doi.org/10.1111/jdv.16948 DB - PRIME DP - Unbound Medicine ER -