Olumiant ® (baricitinib) tabletter

För fullständig produktresumé för Olumiant se FASS.

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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

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

In 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. Most cases of hepatic transaminase elevations were asymptomatic and transient.2

In treatment-naïve patients, the combination of baricitinib with potentially hepatotoxic medicinal products, such as methotrexate, resulted in increased frequency of these 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 %).2

The pattern and incidence of elevation in ALT/AST remained stable over time including in the long-term extension study.2

No cases meeting Hy’s Law criteria were reported in patients receiving BARI treatment.3

Hepatic Analyte Elevations With Baricitinib Use

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

  • data through 13 February 2018, and

  • 10,127 PYE.4,5

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.4,5

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).4,5

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.1,3

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

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.

3. 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

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. Ann Rheum Dis. 2019;78(2):308-309. http://dx.doi.org/10.1136/annrheumdis-2019-eular.691

5. 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.

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 2019 M02 15


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