Olumiant ® (baricitinib) tabletter

För fullständig produktresumé för Olumiant se FASS.

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Olumiant® ▼ (baricitinib): Njurrelaterade biverkningar och analytiska förändringar

En liten, reversibel och dosberoende ökningar av serumkreatinin observerades med baricitinib.

Information from the label

The recommended dose of BARI is 2 mg once daily in patients with creatinine clearance between 30 and 60 mL/min. BARI is not recommended for use in patients with creatinine clearance < 30 mL/min.1

BARI induced a mean increase in serum creatinine levels of 3.8 µmol/L after two weeks of treatment, as compared to placebo, which remained stable thereafter during up to 104 weeks of treatment. This may be due to inhibition of creatinine secretion by BARI in the renal tubules. Consequently, estimates of the glomerular filtration rate based on serum creatinine may be slightly reduced, without actual loss of renal function or the occurrence of renal adverse events.1

Renal-Related Adverse Events

Exposure-adjusted incidence rates were calculated as the number of patients with an event per 100 patient-years of exposure time, with exposure not censored at time of event.2

7-Study Placebo-Controlled Dataset

Description

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.2,3

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).2,3

Renal-Related Adverse Events

Through 24 weeks of assigned treatment or until rescue, the proportion of patients with a renal-related TEAE was

  • 2.6% (EAIR=6.4) in the BARI 4-mg group

  • 2.1% (EAIR=5.4] in the BARI 2-mg group, and

  • 1.9% (EAIR=5.1) in the placebo group.4

4-Study Extended Dataset

Description

The extended dataset included patients with RA randomized to BARI 4 mg (N=479, PYE=698.6) or BARI 2 mg (N=479, PYE=675.6) from 2 phase 2 and 2 phase 3 studies (RA-BUILD, RA-BEACON) and 1 long term extension study (RA-BEYOND). The evaluation time periods included randomization through last available observation incorporating extension data through 13 February 2018 unless otherwise specified. Data were censored at rescue or dose change.2,3

Renal-related Adverse Events

Through 13 February 2018, the proportion of patients with a renal-related TEAE was

  • 4.4% (EAIR=3.1) in the BARI 2-mg group, and

  • 4.8% (EAIR=3.3) BARI 4-mg group.4

All BARI RA Dataset

Description

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.2,3

Renal-related Adverse Events

Through 13 February 2018 renal-related TEAEs were reported in 232 (6.2%, EAIR=2.3) patients. These events included

  • 26 (EAIR=0.3) cases of renal impairment

  • 17 (EAIR=0.2) cases of renal failure

  • 14 (EAIR=0.1) cases of acute kidney injury, and

  • 13 (EAIR=0.1) cases of chronic kidney disease.4

Of the events,

  • 30 (0.8%) were reported as SAEs

  • 25 (0.7%) led to temporary interruption of study treatment, and 

  • 3 (0.1%) led to permanent discontinuation of study treatment.4

Serum Creatinine Mean Values

5-Study Pooled Dataset

Description

The 5-study pooled dataset included patients with RA randomized to BARI 4 mg or placebo from 1 phase 2 study and 4 phase 3 studies (RA-BEAM, RA-BUILD, RA-BEACON and RA-BALANCE). Data includes a long-term extension study (RA-BEYOND) with data through 13 February 2018.4

BARI 2 mg data is pooled from 3 of these studies in which both BARI 2 mg and BARI 4 mg were options during randomization (1 phase 2 studies as well as RA-BUILD and RA-BEACON).4

Mean Change in Serum Creatinine

In the 5-study pooled dataset, the LSM (SE) change from baseline to week 24 in serum creatinine was

  • 5.8 (0.3) μmol/L in the BARI 4-mg group (n=994)

  • 4.3 (0.5) μmol/L in the BARI 2-mg group (n=412), and

  • 0.0 (0.0) μmol/L in the placebo group (n=617).4

Reversibility of Elevated Serum Creatinine

For patients with at least 1 follow-up observation following the last dose of BARI (n=666 through 10 August 2015), mean (SD) and median creatinine values declined towards baseline compared with last on-treatment measurements: mean change = -3.1 (11.1) μmol/L; median change = -3.0 μmol/L.4

Mechanism of Increases in Serum Creatinine With Baricitinib Use

In vitro experiments indicated that BARI may competitively inhibit tubular secretion of creatinine. However, the mechanism of the small, reversible, and dose-dependent increases in serum creatinine observed with BARI treatment has not been fully characterized.4,5

References

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

2. 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.

3. 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

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

5. Zhang Y, Warren MS, Zhang X, et al. Impact on creatinine renal clearance by the interplay of multiple renal transporters: a case study with INCB039110. Drug Metab Dispos. 2015;43(4):485-489. http://dx.doi.org/10.1124/dmd.114.060673

Glossary

BARI = baricitinib

DMARD = disease-modifying antirheumatic drug

EAIR = exposure-adjusted incidence rate

LSM = least squares mean

MTX = methotrexate

PYE = patient-years of exposure

RA = rheumatoid arthritis

SAE = serious adverse event

TEAE = treatment-emergent adverse event

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 M03 14


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