Olumiant ® (baricitinib)

This information is intended for UK registered healthcare professionals only as a scientific exchange in response to your search for information.For current prescribing information for all Lilly products, including Summaries of Product Characteristics, Patient Information Leaflets and Instructions for Use, please visit: www.medicines.org.uk (England, Scotland, Wales) or www.emcmedicines.com/en-GB/northernireland/ (Northern Ireland).

Olumiant® (baricitinib) in Alopecia Areata: What is the Incidence of Major Cardiovascular Events?

In the alopecia areata clinical trials, there was one reported major adverse cardiovascular event (MACE) [IR 0.07].

UK_cFAQ_BAR132C_MACE_AA
UK_cFAQ_BAR132C_MACE_AA
en-GB

Safety Profile of Baricitinib for the Risk of Major Adverse Cardiovascular Events

In a large, randomized, postmarketing safety study of another Janus kinase (JAK) inhibitor in rheumatoid arthritis (RA) patients 50 years of age and older with at least one cardiovascular (CV) risk factor, a higher rate of major adverse cardiovascular events (MACE) defined as cardiovascular death, non-fatal myocardial infarction (MI), and non-fatal stroke was observed with the JAK inhibitor compared to those treated with TNF blockers. Patients who are current or past smokers are at additional increased risk.1,2

Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with baricitinib, particularly in patients who are current or past smokers and patients with other CV risk factors. Patients should be informed about the symptoms of serious CV events and the steps to take if they occur. 1

Incidence of Major Adverse Cardiovascular Events (MACE) in the Baricitinib Alopecia Areata Clinical Trials

Incidence of MACE

In the baricitinib (BARI) alopecia areata (AA) clinical trials, there was one reported MACE [IR 0.07] up to data cut-off of March 24, 2021 for BRAVE-AA2 and March 31, 2021 for BRAVE-AA1.

36-Week Placebo Controlled BARI AA

In the 36-week placebo-controlled period there was 1 MACE in the baricitinib 2 mg group, an acute MI approximately 9 months after starting baricitinib.3

The patient was a 48 year old male with multiple risk factors including current tobacco use, obesity, hypercholesterolemia, atrial fibrillation, and hypertension. Treatment was temporarily interrupted for 4 days while patient underwent a coronary revascularization procedure (reported as another cardiovascular event as seen below), and then resumed.3

Extended BARI AA analysis set

In the Extended BARI AA analysis set up to data cut-off of March 24, 2021, for BRAVE-AA2 and March 31, 2021, for BRAVE-AA1, no additional MACE (baricitinib 2 mg incidence rate [IR] 0.25; baricitinib 4 mg IR 0) were reported.3 

All BARI AA Analysis Set

In the All BARI AA analysis set up to data cut-off of March 24, 2021, for BRAVE-AA2 and March 31, 2021, for BRAVE-AA1, no additional MACE (IR 0.07) were reported.3

Incidence of Other Cardiovascular Events

36-Week Placebo Controlled BARI AA

There were 2 cases of other cardiovascular events. Additional details can be seen in Cases of Other Cardiovascular Events Reported in the 36-Week Placebo Controlled BARI AA Dataset.

Cases of Other Cardiovascular Events Reported in the 36-Week Placebo Controlled BARI AA Dataset3

Other cardiovascular event

Age

Dose

Risk Factors

Outcome

Ventricular tachycardia

70

Baricitinib 2 mga

Obesity
Hyperlipidemia
Palpitations

Permanent discontinuation of study drug
Recovered from event after 6 days

Coronary revascularizationb

48

Baricitinib 2 mg

Current tobacco use
Obesity
Hypercholesterolemia
Atrial fibrillation
Hypertension

Treatment resumed after revascularization procedure

Abbreviation: MACE = major adverse cardiovascular event

aPatient was randomized to baricitinib 4 mg, but dose reduced to baricitinib 2 mg due to renal function.

bThis event was linked to the case of MACE listed above.

Extended BARI AA Analysis Set

In the Extended BARI AA analysis set, no additional cardiovascular events (baricitinib 2 mg IR 0.25; baricitinib 4 mg IR 0.31) were reported.3

All BARI AA Analysis Set

In the All BARI AA analysis set, no additional cardiovascular events (IR 0.21) were reported.3

Additional Information Relevant to Major Adverse Cardiovascular Events

Assessment of MACE and Other Cardiac Events

Events were identified by the investigative site or through medical review and were sent to a blinded, external Clinical Event Committee for adjudication. These events included

  • potential MACE, including
    • cardiovascular death
    • MI, and
    • stroke
  • other cardiovascular events, including
    • transient ischemic attack
    • hospitalization for unstable angina
    • hospitalization for heart failure
    • serious arrhythmia
    • resuscitated sudden death
    • cardiogenic shock, and
    • coronary revascularizations, such as coronary artery bypass graft or percutaneous coronary intervention.3

Alopecia Areata Clinical Trial Exclusion Criteria

In the AA clinical trials, patients were excluded if they had

  • uncontrolled arterial hypertension characterized by a repeated systolic blood pressure >160 mm Hg or diastolic pressure >100 mm Hg in a seated position
  • a history of VTE, or are considered at high risk for VTE, as deemed by the investigator, or have 2 or more of the following risk factors for VTE:
    • aged >65 years
    • body mass index (BMI) >35 kg/m2
    • oral contraceptive use AND current smoker status
  • screening electrocardiogram abnormalities that, in the opinion of the investigator, are clinically significant and indicate an unacceptable risk for the patient's participation in the study
  • a history or presence of cardiovascular or other serious and/or unstable illness that, in the opinion of the investigator, could constitute an unacceptable risk or interfere with the interpretation of data, or
  • experienced within 12 weeks of screening
    • a myocardial infarction
    • unstable ischemic heart disease
    • stroke, or
    • New York Heart Association Stage III/IV heart failure.4

Description of the Clinical Trials

The baricitinib alopecia areata (AA) clinical trial program includes

The incidence of MACE in the BRAVE-AA trials were reported in 3 integrated safety datasets including the

  • 36-week placebo-controlled BARI AA dataset with patients exposed to placebo, baricitinib 2 mg, and baricitinib 4 mg from randomization to week 36
  • extended BARI AA dataset with patients exposed to baricitinib 2 mg or 4 mg from randomization to dose or treatment change, or data cut-off, and
  • All-BARI-AA dataset with all patients exposed to any baricitinib dose (1-mg, 2-mg, or 4-mg) at any time during the studies.7

Safety data were integrated from the BRAVE-AA1 Phase 2 and 3 cohorts (data cut-off March 31, 2021) and from BRAVE-AA2 (data cut-off March 24, 2021).7

More details on patient exposure and censoring rules in each dataset are provided in Integrated Analysis Datasets Used to Evaluate Safety in Alopecia Areata Clinical Trials .

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.8

References

1Olumiant [package insert]. Indianapolis, IN: Eli Lilly and Company; 2022.

2Ytterberg SR, Bhatt DL, Mikuls TR, et al; ORAL Surveillance Investigators. Cardiovascular and cancer risk with tofacitinib in rheumatoid arthritis. N Engl J Med. 2022;386(4):316-326. http://dx.doi.org/10.1056/NEJMoa2109927

3Data on file, Eli Lilly and Company and/or one of its subsidiaries.

4King B, Ohyama M, Kwon O, et al; BRAVE-AA investigators. Two phase 3 trials of baricitinib for alopecia areata. N Engl J Med. 2022;386(18):1687-1699. https://doi.org/10.1056/nejmoa2110343

5A study of baricitinib (LY3009104) in adults with severe or very severe alopecia areata (BRAVE-AA2). ClinicalTrials.gov identifier: NCT03899259. Updated January 26, 2022. Accessed March 4, 2022. https://clinicaltrials.gov/ct2/show/NCT03899259

6A study of baricitinib (LY3009104) in participants with severe or very severe alopecia areata (BRAVE-AA1). ClinicalTrials.gov identifier: NCT03570749. Updated February 3, 2022. Accessed March 4, 2022. https://clinicaltrials.gov/ct2/show/study/NCT03570749

7King B, Mostaghimi A, Shimomura Y, et al. Integrated safety analysis of baricitinib in adults with severe alopecia areata from two randomized clinical trials. Poster presented at: Annual Meeting of the American Academy of Dermatology Association (AAD); March 25-29, 2022; Boston, MA. Accessed April 29, 2022. https://aad-eposters.s3.amazonaws.com/AM2022/poster/33966/Integrated+safety+analysis+of+baricitinib+in+adults+with+severe+alopecia+areata+from+two+randomized+clinical+trials.pdf

8Olumiant [summary of product characteristics]. Eli Lilly Nederland B.V., The Netherlands.

Appendix

Description of Integrated Safety Dataset

Integrated Analysis Datasets Used to Evaluate Safety in Alopecia Areata Clinical Trials3,7 

Analysis Set

Description

36-Week placebo-controlled BARI AA

Assesses BARI 4 mg, BARI 2 mg, and placebo.

Includes patients from the phase 2/3 BRAVE-AA1 and phase 3 BRAVE-AA2 studies who were randomized to

  • BARI 4 mg (n=540, PYE=363.4)
  • BARI 2 mg (n=365, PYE=240.6), or
  • placebo (n=371, PYE=243.2).

Evaluation time period included randomization to week 36.

Extended BARI AA

Assesses BARI 4 mg and BARI 2 mg including extended evaluations.

Includes patients from the phase 2/3 BRAVE-AA1 and phase 3 BRAVE-AA2 studies who were randomized to

  • BARI 4 mg (n=540, PYE=624.3), or
  • BARI 2 mg (n=365, PYE=371.5).

Evaluation time period included randomization up to data cutoff, March 24, 2021 for BRAVE-AA2 and March 31, 2021 for BRAVE-AA1. Data were censored after a patient was switched to another dose or treatment.

All BARI AA

No between-group assessments.

Includes 1244 (total PYE=1362.2) patients from the phase 2/3 BRAVE-AA1 and phase 3 BRAVE-AA2 studies who were exposed to any BARI dose, including

  • BARI 4 mg (n=938, PYE=858.9)
  • BARI 2 mg (n=564, PYE=488.9), or
  • BARI 1 mg (n=28, PYE=14.6).

Evaluation time period included any time points during the studies either from randomization or from switch or rescue from placebo.

Abbreviations: AA = alopecia areata; BARI = baricitinib; PYE = patient-years of exposure.

Date of Last Review: 15 February 2022


Contact Lilly

Call or Email us

If you want to ask a Medical Information question or you want to report an adverse event or product complaint you can call us or email us at ukmedinfo@lilly.com

Available Mon - Fri, 10am - 4pm, excluding Bank Holidays

Or you can

Chat with Us

Click to Chat is Offline

If you have a question, you can chat online with a Lilly Medical Information professional.

Submit a request