Olumiant ® ▼ (baricitinib)

This information is intended for UK registered healthcare professionals only as a scientific exchange in response to your search for information. Please refer to the link for full prescribing information: Olumiant Summary of Product Characteristics (SmPC)

Olumiant® ▼ (baricitinib): Incidence of Eczema Herpeticum in Atopic Dermatitis

Eczema herpeticum did occur in patients treated with baricitinib in the atopic clinical trials. Most cases were mild or moderate.

Warnings and Precautions Related to Infections and Viral Reactivation

Infections

Baricitinib is associated with an increased rate of infections such as upper respiratory tract infections compared to placebo. In rheumatoid arthritis clinical studies, in treatment naïve patients, combination with methotrexate resulted in increased frequency of infections compared to baricitinib monotherapy.1

The risks and benefits of treatment with baricitinib should be carefully considered prior to initiating therapy in patients with active, chronic or recurrent infections.1

If an infection develops, the patient should be monitored carefully and baricitinib therapy should be temporarily interrupted if the patient is not responding to standard therapy. Baricitinib treatment should not be resumed until the infection resolves.1

Viral Reactivation

Viral reactivation, including cases of herpes virus reactivation (e.g., herpes zoster, herpes simplex), were reported in clinical studies.1

Risk of Eczema Herpeticum in Patients With Atopic Dermatitis

Patients with AD have an increased risk of bacterial and viral infections, both cutaneous and non-cutaneous, due to defective skin barrier and immunologic dysregulation.2 Eczema herpeticum (synonymous with Kaposi’s varicelliform eruption) is an acute, disseminated infection of the skin, most commonly caused by herpes simplex virus 1, and represents a typical complication of AD occurring in approximately 3% of patients with AD.3

Interferons are the first line of host defense against viral infections. There is an increased risk of recurrent and disseminated viral infections, including herpes simplex and herpes zoster, related to the insufficient production of IFNs with down regulation of the receptor, especially in patients with AD with a history of eczema herpeticum.4,5

Clinical Trial Exclusion Criteria Related to Eczema Herpeticum

In the phase 3 AD clinical trial program, patients were excluded if they had

  • symptomatic herpes simplex at time of randomization

  • a history of eczema herpeticum within 12 months prior to screening, or 

  • a history of 2 or more episodes of eczema herpeticum in the past.6,7 

Incidence of Eczema Herpeticum in the Atopic Dermatitis Clinical Development Program

In the AD clinical trials, both eczema herpeticum and Kaposi's varicelliform eruption were captured as adverse event preferred terms. For this discussion, the 2 preferred terms were combined and presented singularly as eczema herpeticum.6,7

The integrated datasets used to evaluate cases of eczema herpeticum are described in Table 1.

Placebo-Controlled Period

Through 16 weeks, the proportion of patients with treatment-emergent eczema herpeticum was

  • significantly higher in the BARI 4 mg group than the BARI 2 mg group (p≤.05), and

  • not significantly different between

    • BARI 2 mg (n=1) and placebo (n=4), or

    • BARI 4 mg (n=7) and placebo (n=4).6,7

All Baricitinib-Treated Patients With Extended Data

Of the 2531 patients treated across all BARI doses studied in AD, 43 had 50 treatment-emergent events of eczema herpeticum. Of these 50 events

  • 41 were mild to moderate in severity

  • 11 were reported as serious adverse events including

    • 2 with BARI 1 mg

    • 3 with BARI 2 mg, and

    • 6 with BARI 4 mg treatment

  • 44 occurred while receiving concomitant TCS therapy 

  • 68% involved 10% or less BSA

  • 68% occurred while AD was poorly controlled (IGA 3 or 4)

  • 15 led to treatment interruption, and

  • 2 led to permanent discontinuation.6,7

Of the 43 patients with treatment-emergent eczema herpeticum

  • 6 were receiving BARI 1 mg (N=538)

  • 17 were receiving BARI 2 mg (N=1580), and

  • 20 were receiving BARI 4 mg (N=914).6

Integrated Safety Analysis Datasets

Table 1. Integrated Analysis Datasets Used to Evaluate Safety in Atopic Dermatitis Clinical Trials6,7

Analysis Set

Description

BARI 2 mg Placebo-Controlled

Studies: JAHG, BREEZE-AD1, BREEZE-AD2, BREEZE- AD4, BREEZE- AD5, and BREEZE-AD7

Compares BARI 2 mg vs placebo

Includes patients with AD from 1 phase 2 and 5 phase 3 studies who were randomized to

  • BARI 2 mg (n=721, PYE=210.6), or

  • placebo (n=889, PYE=252.7).

Treatment period was 0 to 16 weeks.

BARI 4 mg Placebo-Controlled

Studies: JAHG, BREEZE-AD1, BREEZE-AD2, BREEZE- AD4, and BREEZE-AD7

Compares BARI 4 mg vs placebo

Includes patients with AD from 1 phase 2 and 4 phase 3 studies who were randomized to

  • BARI 4 mg (n=489, PYE=147.1), or

  • placebo (n=743, PYE=211.8).

Treatment period was 0 to 16 weeks.

BARI 2 mg vs 4 mg

Studies: JAHG, BREEZE-AD1, BREEZE-AD2, BREEZE-AD4, and BREEZE-AD7

Compares BARI 2 mg vs BARI 4 mg through 16 weeks

Includes patients with AD from 1 phase 2 and 4 phase 3 studies who were randomized to

  • BARI 2 mg (n=576, PYE=169.1), or

  • BARI 4 mg (n=489, PYE=147.1).

Treated for 0 to 16 weeks during the placebo-controlled period.

BARI 2 mg vs 4 mg Extended

Studies: JAHG, BREEZE-AD1, BREEZE-AD2, BREEZE-AD4, BREEZE-AD7, and extension study BREEZE-AD3

Compares BARI 2 mg vs BARI 4 mg including extended evaluations

Includes patients with AD from 1 phase 2 and 4 phase 3 studies and any further exposure for those patients in the phase 3 extension study, BREEZE-AD3, who were randomized to

  • BARI 2 mg (n=576, PYE=425.5), or

  • BARI 4 mg (n=489, PYE=459.3).

Data censored at dose or treatment change (rescue, dose switch, or re-randomization to a different BARI dose or placebo) for BREEZE-AD4 and BREEZE-AD3.

All BARI AD

Studies: JAHG, BREEZE-AD1, BREEZE-AD2, BREEZE-AD4, BREEZE-AD5, BREEZE-AD7, and extension studies BREEZE-AD3, BREEZE-AD6

No between-group comparisons

Includes 2531 (total PYE=2247.4) patients with AD from 1 phase 2, 5 phase 3, and 2 phase 3 extension studies who received BARI at a variety of doses, including

  • BARI 1 mg (n=538, PYE=245.9)

  • BARI 2 mg (n=1580, PYE=1129.5), and

  • BARI 4 mg (n=914, PYE=872.8).

Includes all patients who were exposed to any BARI dose at any time during the studies, either from randomization or from switch or rescue from placebo.

 No censoring of data at dose change.

Abbreviations: AD = atopic dermatitis; BARI = baricitinib; PYE = patient-years of exposure.

Note: BARI 1 mg was studied in pivotal trials, however it is not approved. Please refer to section 4.2 of the Olumiant Summary of Product Characteristics for approved dosage.

References

1. Olumiant [summary of product characteristics]. Eli Lilly Nederland B.V., The Netherlands.

2. Langan SM, Abuabara K, Henrickson SE, et al. Increased risk of cutaneous and systemic infections in atopic dermatitis - a cohort study. J Invest Dermatol. 2017;137(6):1375-1377. https://doi.org/10.1016/j.jid.2017.01.030

3. Ong PK, Leung DYM. Bacterial and viral infections in atopic dermatitis: a comprehensive review. Clin Rev Allergy Immunol. 2016;51(3):329-337. https://dx.doi.org/10.1007/s12016-016-8548-5

4. Kwon HJ, Bang DW, Kim EN et al. Asthma as a risk factor for zoster in adults: a population-based case-control study. J Allergy Clin Immunol. 2016;137(5):1406-1412. https://doi.org/10.1016/j.jaci.2015.10.032

5. Traidl S, Kienlin P, Begemann G, et al. Patients with atopic dermatitis and history of eczema herpeticum elicit herpes simplex virus-specific type 2 immune responses. J Allergy Clin Immunol. 2018;141(3):1144-1147.e5. https://doi.org/10.1016/j.jaci.2017.09.048

6. Data on file, Eli Lilly and Company and/or one of its subsidiaries.

7. 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. Published online September 14, 2020. https://doi.org/10.1111/jdv.16948

Glossary

AD = atopic dermatitis

BARI = baricitinib

BSA = body surface area

IFN = interferon

TCS = topical corticosteroids

This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions.

Date of Last Review: January 29, 2021


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