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 Viral Hepatitis in Atopic Dermatitis Clinical Trial Program

Viral reactivation was reported in clinical studies with baricitinib. Screening for viral hepatitis should be performed in accordance with clinical guidelines before starting therapy with baricitinib.

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 Table 1.1

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

    • AST ≥2 times the ULN

    • 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 Table 1 for monitoring details and Table 2 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

Table 1. Hepatitis B virus DNA Monitoring During the Baricitinib Atopic Dermatitis Clinical Trials1a

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

a Patients 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 58 BARI-treated patients with postbaseline HBV DNA testing. Among the 58 patients, 56 (96.6%) had undetectable HBV DNA results postbaseline. Table 2 provides results by baseline serology.1

Table 2. Baseline Hepatitis B Serology in Patients with Postbaseline Hepatitis B Virus Deoxyribonucleic Acid Test1






All BARI AD
N=2531

Baseline Serologya

Postbaseline HBV DNA Tests

Undetectable DNA
n (%)

Detectable < LLOQ
n (%)

Detectable ≥ LLOQ
n (%)

Total

HBsAb+/HBcAb+

45 (95.7)

1b (2.1)

1c (2.1)

47

HBsAb-/HBcAb+

11 (100)

0

0

11

Total

56 (96.6)

1 (1.7)

1 (1.7)

58

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

a Patients 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. 

b Patient was receiving BARI 2 mg in original study and did not continue into long-term extension study. No other laboratory measure of HBV DNA were completed.

c Patient was receiving BARI 4 mg in originating and long-term extension study. In addition to the HBV DNA results, hepatomegaly was found on ultrasound and the patient was discontinued from the study. Approximately 3 weeks later laboratory findings were normal.

The All BARI AD safety dataset 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).1

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. There was no censoring of data at dose change.1

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.

Adverse Events of Viral Hepatitis in Atopic Dermatitis Clinical Trials

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

  • 1 (0.0%) report of positive HBsAg, and

  • 1 (0.0%) report of hepatitis E.1

Warnings and Precautions Related to Infections, Viral Reactivation and Hepatic Transaminase Elevations

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.2

The risks and benefits of treatment with baricitinib should be carefully considered prior to initiating therapy in patients with active, chronic or recurrent infections.2

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.2

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 DMARDs.2

Screening for viral hepatitis should be performed in accordance with clinical guidelines before starting therapy with baricitinib.2

  • 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.2

Hepatic Transaminase Elevations

Dose dependent increases in blood alanine transaminase (ALT) and aspartate transaminase (AST) activity were reported in patients treated with baricitinib compared to placebo. Increases in ALT and AST to ≥ 5 and ≥ 10 x upper limit of normal (ULN) were reported in less than 1 % of patients in clinical trials. In rheumatoid arthritis clinical studies in treatment-naïve patients, combination with methotrexate resulted in increased frequency of hepatic transaminase elevations compared with baricitinib monotherapy.2

If increases in ALT or AST are observed during routine patient management and drug-induced liver injury is suspected, baricitinib should be temporarily interrupted until this diagnosis is excluded.2

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

References

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

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

Glossary

AD = atopic dermatitis

ALT = alanine aminotransferase

AST = aspartate aminotransferase

BARI = baricitinib

DNA = deoxyribonucleic acid

HBcAB = hepatitis B core antibody

HBsAB = hepatitis B surface antibody

HBsAG = hepatitis B surface antigen

HBV = hepatitis B virus

HCV = hepatitis C virus

Ig = immunoglobulin

RNA = ribonucleic acid

ULN = upper limit of normal

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: July 28, 2020


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