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): Major Adverse Cardiovascular Events in Atopic Dermatitis

In the BREEZE-AD clinical development program, treatment with baricitinib was not associated with an increased risk of major adverse cardiovascular events in patients with atopic dermatitis.

Incidence of Cardiovascular Events in Patients With Atopic Dermatitis

Severe and predominantly active atopic eczema are independently associated with modestly increased risk of CV events (approximately 10% to 40% increased risk compared to general population).1,2

Two population-based studies in patients with AD reported the IRs of 3 individual components commonly considered in the composite outcome of MACE

  • MI (IR=0.20)

  • stroke (0.27), and

  • CV death (0.29 to 0.44).1,3

Exclusion Criteria Related to Cardiovascular Events in the BREEZE-AD Clinical Development Program

In the AD phase 3 clinical trials, eligibility criteria relating to CV events excluded patients who

  • have screening electrocardiogram abnormalities that, in the opinion of the investigator or the sponsor, are clinically significant and indicate an unacceptable risk for the patient’s participation in the study

  • have a history of CV disease

  • have a history of recurrent (≥2) VTE or are considered at high risk of VTE as deemed by the investigator

  • within 12 weeks of study entry have experienced

    • MI

    • unstable ischemic heart disease

    • stroke, or

    • have New York Heart Association stage III/IV heart failure.4,5

Cardiovascular Event Adjudication Process in the BREEZE-AD Clinical Development Program

Cardiovascular events were identified by the investigative site or through medical review and were sent to a blinded external Clinical Event Committee for adjudication.4

Positively adjudicated CV events were categorized as either

  • MACE, which included

    • CV death

    • MI

    • stroke, or

  • other CV event, which included

    • transient ischemic attack

    • hospitalization for unstable angina

    • hospitalization for heart failure

    • serious arrhythmia

    • resuscitated sudden death

    • cardiogenic shock, or

    • coronary revascularizations.4,5

Incidence of Major Adverse Cardiovascular Events in the BREEZE-AD Clinical Development Program

The integrated datasets used to evaluate MACE are described in Table 1.

There were no cases of MACE in patients treated with either BARI 2 mg or 4 mg in the placebo-controlled datasets.4

There was 1 MACE (MI) reported in the BARI 2 mg vs 4 mg extended dataset following treatment with BARI 2 mg (IR=0.17).4

In the All BARI AD dataset, there were 2 (0.1%) MACE across all BARI doses with an IR of 0.09; one event was a stroke and the other a MI.4

Warnings and Precautions Related to Lipids

Dose dependent increases in blood lipid parameters were reported in patients treated with baricitinib compared to placebo.6

  • Elevations in LDL cholesterol decreased to pre- treatment levels in response to statin therapy.6

  • Lipid parameters should be assessed approximately 12 weeks following initiation of baricitinib therapy and thereafter patients should be managed according to international clinical guidelines for hyperlipidaemia.6

  • The effect of these lipid parameter elevations on cardiovascular morbidity and mortality has not been determined.6

Further information on this topic is available in section 4.8 of the Olumiant Summary of Product Characteristics.

Integrated Safety Datasets Table

Table 1. Integrated Analysis Datasets Used to Evaluate Safety in Atopic Dermatitis Clinical Trials4,5

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. Silverwood RJ, Forbes HJ, Abuabara K, et al. Severe and predominantly active atopic eczema in adulthood and long term risk of cardiovascular disease: population based cohort study. BMJ. 2018;361:k1786. https://doi.org/10.1136/bmj.k1786

2. Yuan M, Cao WF, Xie XF, et al. Relationship of atopic dermatitis with stroke and myocardial infarction: a meta-analysis. Medicine (Baltimore). 2018;97(49):e13512. https://dx.doi.org/10.1097%2FMD.0000000000013512

3. Andersen YMF, Egeberg A, Gislason GH, et al. Risk of myocardial infarction, ischemic stroke, and cardiovascular death in patients with atopic dermatitis. J Allergy Clin Immunol. 2016;138(1):310-312.e3. https://doi.org/10.1016/j.jaci.2016.01.015

4. 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. https://doi.org/10.1111/jdv.16948

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

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

Glossary

AD = atopic dermatitis

BARI = baricitinib

CV = cardiovascular

IR = incidence rate

IV = intravenous

MACE = major adverse cardiovascular event

MI = myocardial infarction

VTE = venous thromboembolism

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: February 19, 2021


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