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)

How Was the Management of Viral Hepatitis With Olumiant®▼ (baricitinib) in the Rheumatoid Arthritis Clinical Trials?

Screen your patient for viral hepatitis according to clinical guidelines before starting the therapy with baricitinib.

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Warnings and Precautions for Viral Hepatitis 

  • Monitor patients with hepatitis B surface and core antibody without hepatitis B surface antigen for hepatitis B virus deoxyribonucleic acid (HBV DNA).
  • Consult a liver specialist if HBV DNA is detected to determine if the baricitinib treatment should be interrupted.1

Exclusion Criteria for Viral Hepatitis in the Rheumatoid Arthritis Phase 3 Clinical Trials

Hepatitis B

Patients with active hepatitis B infection were excluded from clinical trials. Prior to study enrollment patients were tested and considered positive for hepatitis B with 

  • positive for HBsAg,
  • positive for HBcAb but negative for HBsAb, or
  • positive for HBsAb and positive for HBV DNA.2

Patients were included if they were

  • positive for HBsAb and HBcAb but negative for HBsAg, or
  • positive for HBcAb, negative for HBsAb, and also negative for HBV DNA in Japan.2,3

Hepatitis C

Patients with active hepatitis C infection were excluded from clinical trials. Patients could enroll if they were positive for hepatitis C antibody but negative for hepatitis C virus ribonucleic acid (HCV RNA).3

Other Types of Viral Hepatitis

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

  • current or recent clinically serious viral infection,
  • history of chronic liver disease with the most recent available aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >1.5 times the upper limit of normal (ULN) or the most recent available 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 a risk when taking investigational product or could interfere with the interpretation of data.3

Monitoring of Viral Hepatitis During the Clinical Trials

Monthly HBV DNA testing was performed in Japan for patients with positive screening of HBcAb and/or HBsAb. HBV DNA monitoring was later expanded globally for patients with positive screening HBcAb tested every 3 to 6 months.2

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 immunoglobulin M [IgM])
  • hepatitis B (surface antigen, surface antibody, core antibody, and HBV DNA)
  • hepatitis C antibody
  • hepatitis E antibody (IgG and IgM).3

Hepatitis B Virus DNA Status in the Rheumatoid Arthritis Phase 3 Clinical Trials 

Patient Characteristics, Baseline Serology and HBV DNA Testing

An integrated analysis was conducted in all patients who received one or more doses of baricitinib (BARI) across 4 completed phase 3 studies and 1 ongoing long-term extension study in patients with rheumatoid arthritis. As of the data cut-off date of April 1, 2017, the analysis included 2890 patients representing 6993 patient-years exposure.2

Overall, 269 patients had baseline serology suggestive of prior hepatitis B infection, with the majority from Asian countries (see Baseline Serology Status and Post-Baseline HBV DNA Detectability by Geographical Region).2

Baseline Serology Status and Post-Baseline HBV DNA Detectability by Geographical Region2

Baseline serology status/HBV DNA detectability

Japan
n=371

China
n=50

Taiwan
n=92

South Korea
n=84

North America
n=601

South America
n=655

EU
n=669

Rest of World
n=359

Totala
N=2881

n (%) with post-baseline DNA test

82 (22)

20 (40)

46 (50)

36 (43)

24 (4)

18 (3)

31 (5)

33 (9)

290

HBsAb-/HBcAb-, n (%)

303 (82)

15 (30)

26 (28)

18 (21)

496 (83)

582 (89)

526 (79)

283 (79)

2249

Received post-baseline DNA test

15

0

0

2

8

6

7

7

45

Undetectable HBV DNA test

15

0

0

2

7

6

6

7

43

HBV DNA <29 IU/mL

0

0

0

0

1

0

1

0

2

HBV DNA ≥29 IU/mL

0

0

0

0

0

0

0

0

0

HBsAb+/HBcAb-, n (%)

14 (4)

13 (26)

19 (21)

35 (42)

87 (14)

61 (9)

91 (14)

43 (12)

363

Received post-baseline DNA test

14

0

2

5

4

2

2

1

30

Undetectable HBV DNA test

12

0

2

5

4

2

2

1

28

HBV DNA <29 IU/mL

1

0

0

0

0

0

0

0

1

HBV DNA ≥29 IU/mL

1

0

0

0

0

0

0

0

1

HBsAb+/HBcAb+, n (%)

46 (12)

21 (42)

47 (51)

31 (37)

17 (3)

11 (2)

52 (8)

30 (8)

225

Received post-baseline DNA test

45

19

44

29

11

9

22

22

201

Undetectable HBV DNA test

39

8

38

28

10

8

21

19

171

HBV DNA <29 IU/mL

4

11

3

0

1

0

1

3

23

HBV DNA ≥29 IU/mL

2

0

3

1

0

1

0

0

7

HBsAb-/HBcAb+, n (%)

8 (2)

1 (2)

0

1 (0)

1 (0)

0

3 (1)

14

Received post-baseline DNA test

8

1

0

0

1

1

0

3

14

Undetectable HBV DNA test

7

1

0

0

1

1

0

2

12

HBV DNA <29 IU/mL

1

0

0

0

0

0

0

0

1

HBV DNA ≥29 IU/mL

0

0

0

0

0

0

0

1

1

Abbreviations: EU = European Union; HBcAb = hepatitis B virus core antibody; HBsAb = hepatitis B virus surface antibody; HBV DNA = hepatitis B virus deoxyribonucleic acid.

aTotal number of patients with baseline serology. Data missing for 9 patients, 5 from N. America, 3 from S. America, and 1 from EU.

Post-Baseline HBV DNA Testing

In this analysis, 290 patients had post-baseline HBV DNA testing. Of these patients, 36 (12%) had a detectable HBV DNA result, including

  • 27 patients with qualitative HBV DNA levels (<29 IU/mL), and
  • 9 patients with a quantifiable HBV DNA level (≥29 IU/mL).2

Among the 9 patients who had a quantifiable elevation in HBV DNA, there were

  • 4 patients who discontinued, 3 of whom received antiviral therapy, and
  • 5 patients who continued on BARI, none of whom received antiviral therapy.2

In addition, in these 9 patients there were no investigator reports of hepatitis or elevations in ALT or AST ≥3 times the upper limit of normal.2

Please find the HBV serology and DNA detectability in patients treated with baricitinib in Phase 3 trials in HBV Serology and DNA Detectability in Phase 3 Clinical Trials.

3HBV Serology and DNA Detectability in Phase 3 Clinical Trials2,3

Abbreviations: AE, adverse event; ALT, alanine transaminase; AST, aspartate transaminase; BARI, baricitinib; HBcAb, hepatitis B virus core antibody; HBsAb, hepatitis B virus surface antibody; HBV, hepatitis B virus; DNA, deoxyribonucleic acid; Ph, phase; RA, rheumatoid arthritis; ULN, upper limit of normal.
a Of the 2890 patients, 9 were missing baseline serology (8 missing HBsAb and 1 missing HBcAb). Patients with baseline HbcAb- /HBsAb- results may have received HBV DNA testing as part of monitoring due to a treatment emergent hepatic abnormality or investigator’s discretion.
b Patients with detectable post-baseline HBV DNA were from China (n=11), Japan (n=9), Taiwan (n=6), Israel (n=2), Greece (n=2), Russia (n=2), United States (n=2), Argentina (n=1), and South Korea (n=1).
c Initial randomized treatment assignment was placebo (concomitant csDMARDs, MTX monotherapy, adalimumab [plus MTX]) BARI 2 mg (concomitant csDMARDs), or BARI 4 mg (monotherapy or concomitant csDMARDs). 

d One patient had a single post-baseline detectable HBV DNA result (92, not detected on retest). No antiviral treatment was administered, no hepatic enzymes were elevated or other relevant AEs reported, and the patient continued on BARI.

e 9 patients had quantifiable HBV DNA levels which ranged from 31 to 1547 IU/mL.

f Patient baseline HBV DNA status: not detected (n=17), not tested (n=5), detectable <29 IU/mL (n=1).

g Patient baseline HBV DNA status: not detected (n=5), not tested (n=2).
h Patient baseline HBV DNA status: not detected.

i One patient with ALT/AST ≥3x ULN was discontinued from study due to abnormal liver test. Patient had a single detectable HBV DNA result <29 IU/mL. AST and ALT were ≤3xULN at last observation.

References

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

2Harigai M, Winthrop K, Takeuchi T, et al. Evaluation of hepatitis B virus in clinical trials of baricitinib in rheumatoid arthritis. RMD Open. 2020;6:e001095. http://dx.doi.org/10.1136/rmdopen-2019-001095

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

Date of Last Review: June 09, 2020


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