Olumiant ® (baricitinib) tabletter

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Olumiant® ▼ (baricitinib): Effekter på leveranalyser

Ökningar i ALAT och ASAT observerades hos patienter som behandlades med baricitinib för reumatoid artrit.

Warnings and Precautions Related to Liver Enzyme Elevations

Increases in ALT and AST were observed in RA patients treated with BARI. If increases in ALT or AST are observed and drug-induced liver injury is suspected, BARI should be interrupted until diagnosis is excluded.1

No cases meeting Hy’s Law criteria were reported in patients receiving BARI treatment.2

Hepatic Analyte Elevations With Baricitinib Use in the Rheumatoid Arthritis Clinical Development Program

All BARI RA Dataset

The All BARI RA analysis set included 3770 patients with RA who received BARI at a variety of doses from 1 phase 1, 3 phase 2, and 5 phase 3 studies (RA-BEGIN, RA-BEAM, RA-BUILD, RA-BEACON, RA-BALANCE). Data includes a long-term extension study (RA-BEYOND) with

  • 10,127 total PYE

  • median exposure of 3.1 years

  • maximimum exposure of 6.9 years, and  

  • data through 13 February 2018.3,4

The proportion of patients who had an elevated ALT value of

  • 3X ULN was 4.3%

  • 5X ULN was 1.3%, and

  • 10X ULN was 0.3%.1

The proportion of patients who had an elevated 

  • AST value of ≥3X ULN was 2.5%

  • total bilirubin ≥2X ULN was 0.1%, and

  • ALP ≥1.5X ULN was 6.0%.1

7-Study Placebo-Controlled Dataset

The 7-study pooled dataset included patients with RA randomized to BARI 4 mg (N=1142, PYE=471.8) or placebo (N=1215, PYE=450.8) from 3 phase 2 studies and 4 phase 3 studies (RA-BEAM, RA-BUILD, RA-BEACON and RA-BALANCE). Patients in the placebo group could have been taking background MTX or other conventional DMARDs. Evaluation time periods included through

  • the 12-week placebo-controlled period in phase 2 studies

  • 16 weeks of assigned treatment before any opportunity for rescue therapy in phase 3 studies, and

  • 24 weeks of assigned treatment or until rescue in phase 3 studies.3

Data from BARI 2 mg (N=479, PYE=185.8) is derived from 4 of these studies in which both BARI 2 mg and BARI 4 mg were options during randomization (2 phase 2 studies as well as RA-BUILD and RA-BEACON).3

ALT ≥3X ULN

The proportion of patients who experience an ALT value ≥3X ULN was

  • 1.5% in the BARI 4-mg group

  • 1.5% in the BARI 2-mg group, and

  • 1.2% in the placebo group.1,2

AST ≥3X ULN

The proportion of patients who experience an AST value ≥3X ULN was

  • 1.1% in the BARI 4-mg group

  • 1.3% in the BARI 2-mg group, and

  • 1.1% in the placebo group.1

Total Bilirubin ≥2X ULN

The proportion of patients who experience a total bilirubin value ≥2X ULN was

  • 0% in the BARI 4-mg group

  • 0% in the BARI 2-mg group, and

  • 0.1% in the placebo group.1

ALP ≥1.5X ULN

The proportion of patients who experience an ALP value ≥1.5X ULN was

  • 4.9% in the BARI 4-mg group

  • 2.5% in the BARI 2-mg group, and

  • 4.9% in the placebo group.1

Information From the Label

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.5

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.5

In controlled studies, for up to 16 weeks AST increased ≥ 3 x ULN was uncommonly reported (≥ 1/1,000 to < 1/100 ) and ALT increased ≥ 3 x ULN was commonly reported (≥ 1/100 to < 1/10  ).

Frequency for ALT ≥3 x ULN is based on the pooled rheumatoid arthritis and atopic dermatitis clinical trials. In patients treated with baricitinib in the atopic dermatitis clinical trials, the frequency of those events was uncommon.5

Hepatic Transaminase Elevations

In rheumatoid arthritis controlled studies, for up to 16 weeks, alanine transaminase (ALT) and aspartate transaminase (AST) elevations ≥ 3 x upper limit of normal (ULN) were observed in

  • 1.4 % and 0.8 % of patients treated with Baricitinib, compared to

  • 1.0 % and 0.8 % respectively of patients treated with placebo.5

In treatment-naïve patients, the combination of baricitinib with potentially hepatotoxic medicinal products, such as methotrexate, resulted in increased frequency of hepatic transaminase elevations. For up to 52 weeks, the frequency of ALT and AST elevations ≥ 3 x ULN were

  • greater for the combination treatment of methotrexate and baricitinib (7.5 % and 3.8 %)

  • compared to methotrexate alone (2.9 % and 0.5 %) or

  • baricitinib alone (1.9 % and 1.3 %).5

In atopic dermatitis controlled studies, for up to 16 weeks, ALT and AST elevations ≥ 3 x ULN were uncommonly observed in 0.2 % and 0.5 % of patients treated with baricitinib 4 mg, compared to 0.8 % and 0.8 % respectively of patients treated with placebo.5

Across indications, dose dependent increases in blood ALT and AST activity were also reported in studies extended over week 16. Most cases of hepatic transaminase elevations were asymptomatic and transient. The pattern and incidence of elevation in ALT/AST remained stable over time including in the long-term extension study.5

References

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

2. Smolen JS, Genovese MC, Takeuchi T, et al. Safety profile of baricitinib in patients with active rheumatoid arthritis with over 2 years median time in treatment [published online September 15, 2018]. J Rheumatol. https://dx.doi.org/10.3899/jrheum.171361

3. Genovese MC, Smolen JS, Takeuchi T, et al. Safety profile of baricitinib for the treatment of rheumatoid arthritis over a median of 3 years of treatment: an updated integrated safety analysis. Lancet Rheumatol. 2020;2(6):E347-E357. https://doi.org/10.1016/S2665-9913(20)30032-1

4. Genovese MC, Smolen JS, Takeuchi T, et al. Safety profile of baricitinib for the treatment of rheumatoid arthritis up to 7 years: an updated integrated safety analysis. Presented as an oral presentation at: European League Against Rheumatism (EULAR) Annual Meeting; June 12-15, 2019; Madrid, Spain.

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

Glossary

ALP = alkaline phosphate

ALT = alanine aminotransferase

AST = aspartate aminotransferase

BARI = baricitinib

DMARD = disease-modifying antirheumatic drug

MTX = methotrexate

PYE = patient-years of exposure

RA = rheumatoid arthritis

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.

Datum fӧr senaste ӧversyn 2020 M06 08


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