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): Changes in Lymphocytes, Neutrophils and Platelets

Lymphocyte, neutrophil and platelet counts were routinely monitored during clinical studies of baricitinib.

Mean Changes in Lymphocytes, Neutrophils, and Platelets Over Time

Cell counts for lymphocytes, neutrophils, and platelets were pooled from phase 2 and phase 3 clinical studies, including the long-term extension study period, with data through April 1, 2017.1

Mean Lymphocyte Count Changes

In controlled studies, for up to 16 weeks, increases in platelet counts above 600 x 109 cells/L occurred in 2.0 % of patients treated with baricitinib 4 mg and 1.1 % of patients treated with placebo. No association was observed between increased platelet counts and adverse events of a thrombotic nature. The pattern and incidence of increases in platelet counts remained stable at a higher value than baseline over time including in the long term extension study.2

Mean absolute lymphocyte count increased by 1 week after starting treatment with baricitinib, returned to baseline by week 24, and then remained stable through at least 104 weeks. For most patients, changes in lymphocyte count occurred within the normal reference range.2

Mean lymphocyte counts increased within 4 weeks of initiation of BARI treatment, then stabilized and returned to baseline with prolonged administration.1,3,4

Mean Neutrophil Count Changes

Mean neutrophil counts decreased within 4 weeks of initiation of BARI treatment, followed by stabilization and an increase to baseline after treatment discontinuation.1,3,4

Mean Platelet Count Changes

Mean platelet counts

  • increased early with a peak at week 2

  • returned towards baseline at week 4, and

  • stabilized after week 8 with extended BARI exposure.1,3,4

The pattern and incidence of increased platelet counts remained stable at a higher value than baseline over time. Reversibility of increased platelet count was observed with the return of mean values to baseline after treatment discontinuation.1

Mean Changes in Lymphocytes, Neutrophils, and Platelets Over Time

Cell counts for lymphocytes, neutrophils, and platelets were pooled from phase 2 and phase 3 clinical studies, including the long-term extension study period, with data through April 1, 2017.1

Mean Lymphocyte Count Changes

In controlled studies, for up to 16 weeks, increases in platelet counts above 600 x 109 cells/L occurred in 2.0 % of patients treated with baricitinib 4 mg and 1.1 % of patients treated with placebo. No association was observed between increased platelet counts and adverse events of a thrombotic nature. The pattern and incidence of increases in platelet counts remained stable at a higher value than baseline over time including in the long term extension study.2

Mean absolute lymphocyte count increased by 1 week after starting treatment with baricitinib, returned to baseline by week 24, and then remained stable through at least 104 weeks. For most patients, changes in lymphocyte count occurred within the normal reference range.2

Mean lymphocyte counts increased within 4 weeks of initiation of BARI treatment, then stabilized and returned to baseline with prolonged administration.1,3,4

Mean Neutrophil Count Changes

Mean neutrophil counts decreased within 4 weeks of initiation of BARI treatment, followed by stabilization and an increase to baseline after treatment discontinuation.1,3,4

Mean Platelet Count Changes

Mean platelet counts

  • increased early with a peak at week 2

  • returned towards baseline at week 4, and

  • stabilized after week 8 with extended BARI exposure.1,3,4

The pattern and incidence of increased platelet counts remained stable at a higher value than baseline over time. Reversibility of increased platelet count was observed with the return of mean values to baseline after treatment discontinuation.1

Adverse Events of Lymphopenia and Neutropenia

ALC and ANC should be monitored before treatment initiation and thereafter according to routine patient management.2 

Treatment should not be initiated in patients with an absolute lymphocyte count (ALC) less than 0.5 x 109 cells/L, an absolute neutrophil count (ANC) less than 1 x 109 cells/L, or who have a haemoglobin value less than 8 g/dL. Treatment may be initiated once values have improved above these limits.2

ANC < 1x109 cells/L and ALC < 0.5 x 109 cells/L were reported in less than 1 % of patients in clinical trials. Treatment should be interrupted if ANC < 1 x 109 cellls or ALC < 0.5 x 109 cells/L and may be restarted once values return above there limits.2

Lymphopenia

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

  • 0.6% in the BARI 2-mg group

  • 0.6% in the BARI 4-mg group, and

  • 0.4% in the placebo group.5

Lymphopenia and Infection Risk

Increasing grades of lymphopenia were associated with an increased frequency of infections in the BARI 4-mg group.3

No SAEs of lymphopenia were reported in the integrated analysis datasets.5

Neutropenia

In controlled studies, for up to 16 weeks, neutropenia (<1 x 109 cells/L) was uncommonly reported (≥ 1/1000).2

In controlled studies, for up to 16 weeks, decreases in neutrophil counts below 1 x 109 cells/L occurred in 0.3 % of patients treated with baricitinib compared to 0 % of patients treated with placebo. There was no clear relationship between decreases in neutrophil counts and the occurrence of serious infections. However, in clinical studies, treatment was interrupted in response to ANC < 1 x 109 cells/L. The pattern and incidence of decreases in neutrophil counts remained stable at a lower value than baseline over time including in the long-term extension study.2

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

  • 0.0% in the BARI 2-mg group

  • 0.4% in the BARI 4-mg group, and

  • 0.2% in the placebo group.5

Neutropenia and Infection Risk

Neutropenia did not appear to be associated with a higher risk of serious infections with BARI.5

Thrombocytosis and Thromboembolic Adverse Events

In controlled studies, for up to 16 weeks, thrombocytosis (>600 x 109 cells/L) was commonly reported (≥ 1/100 to <1/10).2

DVT and PE are listed as uncommon in the table of adverse reactions in the summary of product characteristics.2

Events of deep venous thrombosis (DVT) and pulmonary embolism (PE) have been reported in patients receiving baricitinib. Baricitinib should be used with caution in patients with risk factors for DVT/PE, such as older age, obesity, a medical history of DVT/PE, or patients undergoing surgery and immobilisation. If clinical features of DVT/PE occur, baricitinib treatment should be discontinued and patients should be evaluated promptly, followed by appropriate treatment.2

The association between thrombocytosis and adverse events of a thrombotic nature were evaluated in patients from the All BARI RA 12-month safety update analysis set.1

Among the 31 patients in the All BARI RA dataset with a reported adverse event of VTE through September 1, 2016, the proportion of patients with high platelet levels was comparable between patients with VTE vs those without VTE. No association was observed between increased platelet counts and VTE events.1,4

References

1. Kremer J, Huizinga TWJ, Chen L, et al. Analysis of neutrophils, lymphocytes, and platelets in pooled phase 2 and phase 3 studies of baricitinib for rheumatoid arthritis. Poster presented at: European League Against Rheumatism (EULAR) Annual Meeting; June 14-17, 2017; Madrid, Spain.

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

3. Eli Lilly and Company. Lilly FDA Advisory Committee Meeting NDA 207924 Briefing Document. https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/ArthritisAdvisoryCommittee/UCM605062.pdf. Accessed May 2, 2018a. https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/ArthritisAdvisoryCommittee/UCM605062.pdf

4. 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

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

Glossary

ALC = absolute lymphocyte count

ANC = absolute neutrophil count

BARI = baricitinib

RA = rheumatoid arthritis

SAE = serious adverse event

TEAE = treatment-emergent adverse event

VTE = venous thromboembolism

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: October 15, 2018

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