Olumiant ® (baricitinib)

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What was the incidence of viral hepatitis with Olumiant® (baricitinib) in atopic dermatitis?

In all baricitinib treated patients, 3 AE related to viral hepatitis were reported in the AD clinical trials. There was 1 report of positive hepatitis B core antibody, 1 report of positive hepatitis B surface antigen, and 1 report of hepatitis E.

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BREEZE-AD Phase 3 Clinical Trial Protocol Information for Viral Hepatitis

Protocol Criteria Related to Viral Hepatitis

Hepatitis B

Patients with evidence of active or chronic hepatitis B infection were excluded from clinical trials.1

Prior to study enrollment, patients were tested for HBsAg, HBcAb, and HBV DNA. A positive test for hepatitis B virus was defined as

  • positive for HBsAg, or
  • positive for HBcAb and positive for HBV DNA.1

Patients were permitted to enroll if they were positive for HBcAb and negative for HBV DNA. These patients were monitored during the study, see Hepatitis B virus DNA Monitoring During the Baricitinib Atopic Dermatitis Clinical Trials.1

Hepatitis C

Patients with evidence of active or chronic hepatitis C infection were excluded from clinical trials. Patients were excluded if they were positive for anti-hepatitis C antibody with confirmed presence of HCV RNA.1

Patients were permitted to enroll if they had documented anti-HCV treatment for past HCV infection and were HCV RNA negative.1

Other Types of Viral Hepatitis

Other types of viral hepatitis were not specified in the exclusion criteria. However, patients were excluded from participation if they had

  • a current or recent clinically serious viral infection
  • the following lab abnormalities at screening
    • Aspartate aminotransferase (AST) ≥2 times the upper limit of normal (ULN)
    • Alanine aminotransferase (ALT) ≥2 times the ULN
    • total bilirubin ≥1.5 times the ULN, or
  • a history or presence of hepatic disorders or any other serious and/or unstable illness that, in the opinion of the investigator, could constitute an unacceptable risk when taking investigational product or could interfere with the interpretation of data.1

Monitoring of Viral Hepatitis During the Clinical Trials

Hepatitis B Monitoring

Patients who were HBcAb positive and HBV DNA negative (undetectable) at screening had an HBV DNA measurement at week 16, regardless of HBsAb status. See Hepatitis B virus DNA Monitoring During the Baricitinib Atopic Dermatitis Clinical Trials for monitoring details and Baseline Hepatitis B Serology in Patients with Postbaseline Hepatitis B Virus Deoxyribonucleic Acid Test for monitoring results.1

Hepatitis B virus DNA results were classified as

  • undetectable
  • detectable but below the lower limit of quantitation, or
  • detectable above the lower limit of quantitation.1
Hepatitis B virus DNA Monitoringa During the Baricitinib Atopic Dermatitis Clinical Trials1

If...

Then...

a single result was "below limit of quantitation"

the test was repeated within 2 weeks

the repeat test result was "undetectable"

monitoring was repeated based on study schedule

2 or more test results were "below limit of quantitation"

the patient was permanently discontinued from study drug and referred to hepatology specialist

a single test result of "above the limit of quantitation"

the patient was permanently discontinued from study drug and referred to hepatology specialist

Abbreviations: HBcAb = hepatitis B core antibody; HBV = hepatitis B virus; DNA = deoxyribonucleic acid.

aPatients who were HBcAb positive and HBV DNA negative (undetectable) had an HBV DNA measurement at week 16.

Other Types of Viral Hepatitis Monitoring

Serial HCV RNA testing and monitoring for other types of viral hepatitis were not routinely conducted in the clinical studies. However, selected tests may have been obtained in the event of a treatment-emergent hepatic abnormality. These included tests for

  • hepatitis A antibody (total and IgM)
  • hepatitis B (surface antigen, surface antibody, and core antibody)
  • hepatitis C antibody, and
  • hepatitis E antibody (IgG and IgM).1

Hepatitis B Virus DNA Status in the Atopic Dermatitis Clinical Trials

There were 72 baricitinib-treated patients with postbaseline hepatitis B virus (HBV) deoxyribonucleic acid (DNA) testing. Among the 72 patients, 69 (95.8%) had undetectable HBV DNA results postbaseline. Baseline Hepatitis B Serology in Patients with Postbaseline Hepatitis B Virus Deoxyribonucleic Acid Test provides results by baseline serology.1

Baseline Hepatitis B Serology in Patients with Postbaseline Hepatitis B Virus Deoxyribonucleic Acid Test1

All BARI AD
N=2636

Baseline Serology
a

Postbaseline HBV DNA Tests

Undetectable DNA
n (%)

Detectable < LLOD
n (%)

Detectable ≥ LLOD
n (%)

Total

HBsAb+/HBcAb+

51 (94.4)

2 (3.7)

1 (1.9)

54

HBsAb-/HBcAb+

18 (100)

0

0

18

Total

69 (95.8)

2 (2.8)

1 (1.4)

72

Abbreviations: AD = atopic dermatitis; BARI = baricitinib; HBcAb = Hepatitis B core antibody; HBsAb = Hepatitis B surface antibody; HBV DNA = Hepatitis B virus deoxyribonucleic acid; LLOD = lower limit of detection. 

aPatients were permitted to enroll in the atopic dermatitis clinical studies if they were positive for HBcAb and negative for HBV DNA. These patients were monitored during the study with postbaseline HBV DNA testing.

Adverse Events of Viral Hepatitis in Atopic Dermatitis Clinical Trials

The All BARI AD safety dataset includes 2636 (total patient-years of exposure [PYE]=4628.4) patients with AD from 1 phase 2, 5 phase 3, and 2 phase 3 extension studies who received baricitinib at a variety of doses, including

  • BARI 1 mg (n=605, PYE=441.5)
  • BARI 2 mg (n=1703, PYE=2420.9), and
  • BARI 4 mg (n=1012, PYE=1766.8).1,2

Includes all patients who were exposed to any baricitinib dose at any time during the studies, either from randomization or from switch or rescue from placebo. There was no censoring of data at dose change.1

Treatment-emergent adverse events (TEAEs) related to viral hepatitis in the All BARI AD safety dataset included

  • 1 (0.0%) report of positive hepatitis B core antibody (HBcAb)
  • 1 (0.0%) report of positive hepatitis B surface antigen (HBsAg), and
  • 1 (0.0%) report of hepatitis E.1

Baricitinib Label Information 

Warnings and Precautions Related to Infections

Baricitinib is associated with an increased rate of infections such as upper respiratory tract infections compared to placebo. In rheumatoid arthritis clinical studies, combination with methotrexate resulted in increased frequency of infections compared to baricitinib monotherapy.3

The risks and benefits of treatment with baricitinib should be carefully considered prior to initiating therapy in patients with active, chronic or recurrent infections.3

If an infection develops, the patient should be monitored carefully and therapy should be temporarily interrupted if the patient is not responding to standard therapy. Treatment should not be resumed until the infection resolves.3

Warnings and Precautions Related to Viral Reactivation

Viral reactivation, including cases of herpes virus reactivation (e.g., herpes zoster, herpes simplex), were reported in clinical studies. In rheumatoid arthritis clinical studies, herpes zoster was reported more commonly in patients ≥ 65 years of age who had previously been treated with both biologic and conventional disease-modifying antirheumatic drugs (DMARDs).3

Screening for viral hepatitis should be performed in accordance with clinical guidelines before starting therapy with baricitinib.3

  • Patients with evidence of active hepatitis B or C infection were excluded from clinical trials.
  • Patients, who were positive for hepatitis C antibody but negative for hepatitis C virus RNA, were allowed to participate.
  • Patients with hepatitis B surface antibody and hepatitis B core antibody, without hepatitis B surface antigen, were also allowed to participate; such patients should be monitored for expression of hepatitis B virus (HBV) DNA.
  • If HBV DNA is detected, a liver specialist should be consulted to determine if treatment interruption is warranted.

Warnings and Precautions Related to Hepatic Transaminase Elevations

Dose dependent increases in blood alanine transaminase (ALT) and aspartate transaminase (AST) activity were reported in patients treated with baricitinib.3

Increases in ALT and AST to ≥ 5 and ≥ 10 x upper limit of normal (ULN) were reported in clinical trials. In rheumatoid arthritis clinical studies, combination with methotrexate resulted in increased frequency of hepatic transaminase elevations compared with baricitinib monotherapy.3

If increases in ALT or AST are observed during routine patient management and drug-induced liver injury is suspected, treatment should be temporarily interrupted until this diagnosis is excluded.3

Further information on these topics are available in section 4.8 of the Olumiant Summary of Product Characteristics.

References

1Data on file, Eli Lilly and Company and/or one of its subsidiaries.

2Bieber T, Katoh N, Simpson EL, et al. Safety of baricitinib for the treatment of atopic dermatitis over a median of 1.6 and up to 3.9 years treatment: an updated integrated analysis of 8 clinical trials. Poster presented at: 31st Annual European Academy of Dermatology and Venereology Congress; September 7-10, 2022; Milan, Italy.

3Olumiant [summary of product characteristics]. Eli Lilly Nederland B.V., The Netherlands.

Date of Last Review: 11 August 2022


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