Olumiant ® (baricitinib)

This information is intended for UK registered healthcare professionals only as a scientific exchange in response to your search for information.For current prescribing information for all Lilly products, including Summaries of Product Characteristics, Patient Information Leaflets and Instructions for Use, please visit: www.medicines.org.uk (England, Scotland, Wales) or www.emcmedicines.com/en-GB/northernireland/ (Northern Ireland).

Do lymphocyte and neutrophil counts change in patients treated with Olumiant® (baricitinib) for atopic dermatitis?

Mean neutrophil counts decreased but stabilized over the 68-week period, whereas mean lymphocyte counts initially increased with baricitinib and returned to baseline values over the course of the extended period.

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Baricitinib Label Information Related to Neutrophils and Lymphocytes

Warnings and Precautions

Absolute Neutrophil Count (ANC) < 1 x 109 cells/L and Absolute Lymphocyte Count (ALC) < 0.5 x 109 cells/L were reported in less than 1 % of patients in clinical trials.1

Treatment should not be initiated, or should be temporarily interrupted, in patients with an

  • ANC < 1 x 109 cells/L, or
  • ALC < 0.5 x 109 cells/L 

observed during routine patient management.1

Neutropenia

Mean neutrophil counts decreased at 4 weeks and remained stable at a lower value than baseline over time. There was no clear relationship between neutropaenia and the occurrence of serious infections. However, in clinical studies, treatment was interrupted in response to ANC < 1 x 109 cells/L.1 

Changes of Lymphocytes and Neutrophils in the Baricitinib BREEZE-AD Clinical Program

Integrated Safety Datasets

Integrated Analysis Datasets Used to Evaluate Safety in Atopic Dermatitis Clinical Trials describes the integrated datasets that were used to evaluate lymphocyte and neutrophil changes, common terminology criteria for adverse events (CTCAE) grade shifts of abnormal lymphocyte and neutrophil values, and the incidence of lymphopenia and neutropenia.

Mean Changes in Lymphocytes and Neutrophils Over Time

Changes in Lymphocytes Over Time

Mean ALC

Time Course of Lymphocyte Levels in Patients From the BREEZE-AD Clinical Program3

Abbreviations: AD = atopic dermatitis; BARI = baricitinib.

Changes in Neutrophils Over Time

Mean ANC

Time Course of Neutrophil Levels in Patients From the BREEZE-AD Clinical Program3

Abbreviations: AD = atopic dermatitis; BARI = baricitinib.

Patients With CTCAE Grade Shifts and Abnormal Lymphocyte and Neutrophil Values

CTCAE Grade Shifts in Lymphocytes and Neutrophils

Categorical changes in treatment emergent (TE) abnormal laboratory values were analyzed based on the

  • TE shifts in CTCAE grades, and
  • upper limit of normal (ULN) and lower limit of normal (LLN).2

Abnormal Lymphocyte Levels

Significant differences in TE abnormal high were reported in patients treated with baricitinib compared with placebo and between baricitinib doses. No significant differences were observed in TE abnormal low (see column 1 and 2 of Overview of Treatment-Emergent Abnormal Low and High and CTCAE Grade Shifts in Lymphocytes From BREEZE-AD Clinical Development Program).3

Most lymphocyte shifts were to CTCAE grade 1 or 2, and there were no shifts to CTCAE grade 4 (Overview of Treatment-Emergent Abnormal Low and High and CTCAE Grade Shifts in Lymphocytes From BREEZE-AD Clinical Development Program).3

Overview of Treatment-Emergent Abnormal Low and High and CTCAE Grade Shifts in Lymphocytes From BREEZE-AD Clinical Development Program2,3

Treatment-Emergent Abnormal Low
n/NAR (adj %)

Treatment-Emergent Abnormal High
n/NAR (adj %)

Shift From:
Grade <1 to Grade ≥1
n/NAR (%)

Shift From:
Grade <2 to Grade ≥2
n/NAR (%)

Shift From:
Grade <3 to Grade ≥3
n/NAR (%)

Shift From:
Grade <4 to Grade ≥4
n/NAR (%)

16-Week Placebo-Controlled BARI ADa


Placebo, n=743

50/641 (6.3)

18/719 (2.1)

59/593 (9.9)

21/707 (3.0)

1/726 (0.1)

0/727 (0)

BARI 2 mg, n=576

44/496 (7.2)

16/558 (2.3)

51/452 (11.3)

8/557 (1.4)

0/570 (0)

0/570 (0)

BARI 4 mg, n=489

30/414 (5.8)

27/481 (5.0)b

35/387 (9.0)

14/470 (3.0)

3/487 (0.6)

0/487 (0)

BARI 2 mg and 4 mg Extended ADa


BARI 2 mg, n=584

94/503 (15.8)

27/566 (3.9)

102/459 (22.2)

24/565 (4.2)

1/578 (0.2)

0/578 (0)

BARI 4 mg, n=497

79/422 (15.9)

36/489 (6.5)c

87/395 (22.0)

38/478 (7.9)c

4/495 (0.8)

0/495 (0)

All BARI ADde, n/NAR (%)


All doses, N=2636

448/2224 (20.1)

162/2553 (6.3)

491/2052 (23.9)

195/2507 (7.8)

22/2597 (0.8)

0/2601 (0)

Abbreviations: AD = atopic dermatitis; adj = adjusted; BARI = baricitinib; CTCAE = Common Terminology Criteria for Adverse Events; NAR = number of patients at risk for specified abnormality.

aFor the integrated controlled analysis sets where the randomized ratio of patients receiving BARI to placebo or BARI to active control is not the same across all the integrated studies (example 2:1:1:1 vs 1:1:1:1), the study-size adjusted percentages were calculated for the adverse events to provide appropriate direct comparisons between treatment groups.

bp<.05 vs placebo.

cp<.05 BARI 4 mg vs BARI 2 mg.

dAll-BARI AD includes BARI 1-mg, 2-mg, and 4-mg.

eData is up to 3.9 years of treatment.

Abnormal Neutrophil Levels

Significant differences in TE abnormal low/high were reported in patients treated with baricitinib compared with placebo and between baricitinib doses (see column 1 of Overview of Treatment-Emergent Abnormal Low and CTCAE Grade Shifts in Neutrophils From BREEZE-AD Clinical Development Program).3

Most neutrophil shifts were to CTCAE grade 1 or 2, and there were no shifts to CTCAE grade 4 (Overview of Treatment-Emergent Abnormal Low and CTCAE Grade Shifts in Neutrophils From BREEZE-AD Clinical Development Program).3

Overview of Treatment-Emergent Abnormal Low and CTCAE Grade Shifts in Neutrophils From BREEZE-AD Clinical Development Program2,3

Treatment-Emergent Abnormal Low
n/NAR (adj %)

Shift From
Grade <1 to Grade ≥1
n/NAR (%)

Shift From
Grade <2 to Grade ≥2
n/NAR (%)

Shift From
Grade <3 to Grade ≥3
n/NAR (%)

Shift From
Grade <4 to Grade ≥4
n/NAR (%)

16-Week Placebo-Controlled BARI ADa


Placebo, n=743

37/710 (4.5)

34/711 (4.8)

6/723 (0.8)

0/727 (0)

0/727 (0)

BARI 2 mg, n=576

45/556 (6.7)

41/556 (7.4)

8/568 (1.4)

1/570 (0.2)

0/570 (0)

BARI 4 mg, n=489

52/470 (8.9)b

50/471 (10.6)b

14/486 (2.9)c

1/487 (0.2)

0/487 (0)

BARI 2 mg and 4 mg Extended ADa


BARI 2 mg, n=584

65/564 (9.5)

61/564 (10.8)

18/576 (3.1)

2/578 (0.3)

0/578 (0)

BARI 4 mg, n=497

97/478 (17.0)d

93/479 (19.4)d

33/494 (6.7)e

6/495 (1.2)e

0/495 (0)

All BARI ADfg, n/NAR (%)


All doses, N=2636

375/2469 (15.2)

363/2475 (14.7)

127/2576 (4.9)

13/2595 (0.5)

0/2600 (0)

Abbreviations: AD = atopic dermatitis; adj = adjusted; BARI = baricitinib; CTCAE = Common Terminology Criteria for Adverse Events; NAR = number of patients at risk for specified abnormality.

aFor the integrated controlled analysis sets where the randomized ratio of patients receiving BARI to placebo or BARI to active control is not the same across all the integrated studies (example 2:1:1:1 vs 1:1:1:1), the study-size adjusted percentages were calculated for the adverse events to provide appropriate direct comparisons between treatment groups.

bp<.001 vs placebo.

cp<.05 vs placebo.

dp<.001 BARI 4 mg vs BARI 2 mg.

ep<.05 BARI 4 mg vs BARI 2 mg.

fAll-BARI AD includes BARI 1-mg, 2-mg, and 4-mg.

gData is up to 3.9 years of treatment.

Interruption of Treatment During Atopic Dermatitis Clinical Trials

In phase 3 clinical trials, study treatment was temporarily interrupted in patients with an

  • ALC <0.5 billion cells/L (500 cells/mm3), or
  • ANC <1.0 billion cells/L (1000 cells/mm3).3

In the phase 3 clinical trials, study treatment was permanently discontinued in patients with an

  • ALC <0.2 billion cells/L (200 cells/mm3), or
  • ANC <0.5 billion cells/L (500 cells/mm3).3

Adverse Events of Lymphopenia and Neutropenia

Overview of Treatment-Emergent Adverse Events of Lymphopenia and Neutropenia provides rates of treatment-emergent adverse events (TEAEs) as well as treatment interruption and permanent discontinuation of study treatment due to TEAEs of lymphopenia and neutropenia for all of the integrated analysis datasets.

Overview of Treatment-Emergent Adverse Events of Lymphopenia and Neutropenia3

Lymphopenia

Neutropenia


TEAE

Temporary Interruption of Treatment

Permanent DC of Treatment

TEAE

Temporary Interruption of Treatment

Permanent DC of Treatment

16-Week Placebo-Controlled BARI ADa, n (adj %)



Placebo, n=743

4 (0.4) 

0

3 (0.3)

2 (0.2)

0

0

BARI 2 mg, n=576

2 (0.3)

0

0

1 (0.1)

0

1 (0.1)

BARI 4 mg, n=489

3 (0.4)

0

0

2 (0.2)

0

0

BARI 2 mg and 4 mg Extended ADa, n (adj %) [adj IR]



BARI 2 mg, n=584

4 (0.5) [0.6]

1 (0.1) [0.1]

0

2 (0.2) [0.3]

0

1 (0.1) [0.1]

BARI 4 mg, n=497

6 (0.9) [0.7]

1 (0.1) [0.1]

0

7 (1.0) [0.9]

3 (0.5) [0.4]

0

All BARI ADbc, n (%) [IR]



All doses, N=2636

22 (0.8) [0.5]

9 (0.3) [0.2]

0

19 (0.7) [0.4]

4 (0.2) [0.1]

1 (0) [0]

Abbreviations: AD = atopic dermatitis; adj = adjusted; BARI = baricitinib; DC = discontinuation; IR = incidence rate; TEAE = treatment-emergent adverse event.

aFor the integrated controlled analysis sets where the randomized ratio of patients receiving BARI to placebo or BARI to active control is not the same across all the integrated studies (eg, 2:1:1:1 vs 1:1:1:1), the study-size–adjusted percentages were calculated for the adverse events to provide appropriate direct comparisons between treatment groups.

bAll-BARI AD includes BARI 1-mg, 2-mg, and 4-mg.

cData is up to 3.9 years of treatment.

Integrated Safety Dataset Table

Integrated Analysis Datasets Used to Evaluate Safety in Atopic Dermatitis Clinical Trials2-5

Analysis Set

Description

16-Week Placebo-Controlled BARI AD

Studies: JAHG, BREEZE-AD1, BREEZE-AD2, BREEZE-AD4, and BREEZE-AD7

Compares BARI 2 mg, BARI 4 mg and placebo.

Includes patients with AD from 1 phase 2 and 4 phase 3 studies who were randomized to

  • BARI 2 mg (n=576, PYE=169.1)
  • BARI 4 mg (n=489, PYE=147.1), or
  • placebo (n=743, PYE=211.8).

Treated for 0 to 16 weeks during the placebo-controlled period.

BARI 2 mg and 4 mg Extended ADa

Studies: JAHG, BREEZE-AD1, BREEZE-AD2, BREEZE-AD4, BREEZE-AD7, and extension study BREEZE-AD3

Compares BARI 2 mg vs BARI 4 mg including extended evaluations

Includes patients with AD from 1 phase 2 and 4 phase 3 studies and any further exposure for those patients in the phase 3 extension study, BREEZE-AD3, who were randomized to

  • BARI 2 mg (n=584, PYE=727.1), or
  • BARI 4 mg (n=497, PYE=800.1).

Data censored at dose or treatment change (rescue, dose switch, or re-randomization to a different BARI dose or placebo) for BREEZE-AD4 and BREEZE-AD3.

All BARI ADb

Studies: JAHG, BREEZE-AD1, BREEZE-AD2, BREEZE-AD4, BREEZE-AD5, BREEZE-AD7, and extension studies BREEZE-AD3, BREEZE-AD6

No between-group comparisons

Includes 2636 (total PYE=4628.4) patients with AD from 1 phase 2, 5 phase 3, and 2 phase 3 extension studies who received BARI at a variety of doses, including

  • BARI 1 mg (n=605, PYE=441.5)
  • BARI 2 mg (n=1703, PYE=2420.9), and
  • BARI 4 mg (n=1012, PYE=1766.8).

Includes all patients who were exposed to any BARI dose at any time during the studies, either from randomization or from switch or rescue from placebo.

 No censoring of data at dose change.

Abbreviations: AD = atopic dermatitis; BARI = baricitinib; PYE = patient-years of exposure.

aData cut as of November 3, 2021 for BREEZE-AD3 and December 15, 2021 for BREEZE-AD4

bData cut as of November 3, 2021 for BREEZE-AD3, December 15, 2021 for BREEZE-AD4, and December 21, 2021 for BREEZE AD6

Note: BARI 1 mg was studied in pivotal trials, however it is not approved. Please refer to section 4.2 of the Olumiant Summary of Product Characteristics for approved dosage.

References

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

2Bieber T, Thyssen JP, Reich K, et al. Pooled safety analysis of baricitinib in adult patients with atopic dermatitis from 8 randomized clinical trials. J Eur Acad Dermatol Venereol. 2021;35(2):476-485. https://doi.org/10.1111/jdv.16948

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

4King B, Maari C, Lain E, et al. Extended safety analysis of baricitinib 2 mg in adult patients with atopic dermatitis: an integrated analysis from eight randomized clinical trials. Am J Clin Dermatol. 2021;22(3):395-405. https://doi.org/10.1007/s40257-021-00602-x

5Bieber T, Katoh N, Simpson EL, et al. Safety of baricitinib for the treatment of atopic dermatitis over a median of 1.6 and up to 3.9 years treatment: an updated integrated analysis of 8 clinical trials. Poster presented at: 31st Annual European Academy of Dermatology and Venereology Congress; September 7-10, 2022; Milan, Italy.

Date of Last Review: 22 August 2022


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