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): Permanent Discontinuations and Deaths in Atopic Dermatitis Clinical Trials

In patients treated with baricitinib, adverse events leading to permanent discontinuation were <3% through 16 weeks, and <5% with extended treatment.

Adverse Events Leading to Permanent Discontinuation

Table 2 describes the integrated safety datasets used to evaluate AEs leading to permanent discontinuations.

Placebo-Controlled Period

Through 16 weeks, AEs leading to permanent discontinuation were seen in less than 3% of patients in any treatment group with no significant difference between BARI 2 mg, BARI 4 mg, or placebo. Table 1 provides more details including AEs leading to permanent discontinuations by SOC.1

 

Table 1. Adverse Events Leading to Permanent Discontinuation of Treatment 1

 

 

 

 

 

 

 

 

 

 

 

BARI 2 mg Placebo-Controlleda
n (adj %)
b

BARI 4 mg Placebo-Controlleda
n (adj %)
b

BARI 2 mg vs 4 mga
n (adj %)
b

BARI 2 mg vs 4 mg ext
n (adj %)
b [adj IR]

All BARI AD
n (%) [IR]


Placebo
n=889

BARI 2 mg
n=721

Placebo
n=743

BARI 4 mg
n=489

BARI 2 mg
n=576

BARI 4 mg
n=489

BARI 2 mg
n=576

BARI 4 mg
n=489

All Doses
N=2531

AEs Leading to Permanent D/C

17 (1.8)

14 (1.9)

13 (1.4)

15 (2.1)

10 (1.5)

15 (2.1)

18 (2.4 ) [3.6]

27 (4.4) [5.5]c

105 (4.1) [4.6]

SAEs Leading to Permanent D/C

4 (0.4)

4 (0.5)

4 (0.4)

2 (0.2)

3 (0.4)

2 (0.2)

6 (0.8) [1.2]

7 (1.3) [1.3]

35 (1.4) [1.5]

By System Organ Class

Skin and subcutaneous tissue disorders

4 (0.4)

2 (0.2)

3 (0.3)

5 (0.7)

2 (0.2)

5 (0.7)

3 (0.4) [0.6]

9 (1.4) [1.7]

27 (1.1) [1.2]

Infections and infestations

3 (0.3)

2 (0.3)

2 (0.2)

2 (0.4)

2 (0.3)

2 (0.4)

5 (0.6) [0.9]

6 (1.2) [1.5]

20 (0.8) [0.9]

Investigationsd

2 (0.3)

2 (0.3)

1 (0.2)

3 (0.4)

1 (0.2)

3 (0.4)

1 (0.2) [0.3]

6 (0.9) [1.1]

15 (0.6) [0.6]e

Gastrointestinal disorders

1 (0.1)

1 (0.1)

0

1 (0.1)

1 (0.1)

1 (0.1)

2 (0.2) [0.3]

1 (0.1) [0.2]

8 (0.3) [0.3]

Nervous system disorders

2 (0.2)

2 (0.2)

2 (0.2)

1 (0.1)

0

1 (0.1)

0

1 (0.1) [0.2]

5 (0.2) [0.2]

Cardiac disorders

0

0

0

0

0

0

1 (0.1) [0.2]

0

4 (0.2) [0.2]

General disorders

0

1 (0.1)

0

0

1 (0.1)

0

2 (0.2) [0.3]

0

4 (0.2) [0.2]

Neoplasmf

2 (0.2)

0

2 (0.2)

0

0

0

0

0

3 (0.1) [0.1]

Respiratory, thoracic and mediastinal disorders

0

0

0

2 (0.2)

0

2 (0.2)

0

1 (0.1) [0.2]

3 (0.1) [0.1]

Vascular disorders

0

0

0

0

0

0

1 (0.2) [0.3]

1 (0.2) [0.2]

3 (0.1) [0.1]

Blood and lymphatic system disorders

3 (0.3)

1 (0.1)

3 (0.3)

0

1 (0.1)

0

1 (0.1) [0.2]

0

2 (0.1) [0.1]

Congenital, familial, and genetic disorders

0

1 (0.1)

0

0

0

0

0

0

2 (0.1) [0.1]

Eye disorders

0

1 (0.2)

0

0

1 (0.2)

0

1 (0.2 ) [0.3]

0

2 (0.1) [0.1]

Injury, poisoning, and procedural complications

0

0

0

0

0

0

0

0

2 (0.1) [0.1]

Psychiatric disorders

0

1 (0.2)

0

0

1 (0.2)

0

1 (0.2) [0.3]

0

2 (0.1) [0.1]

Ear and labyrinth disorders

0

0

0

0

0

0

0

0

1 (0.0) [0.0]

Hepatobiliary disorders

0

0

0

0

0

0

0

1 (0.2) [0.2]

1 (0.0) [0.0]

Renal and urinary disorders

0

0

0

1 (0.2)

0

1 (0.2)

0

1 (0.2) [0.2]

1 (0.0) [0.0]

Abbreviations: AD = atopic dermatitis; adj = adjusted;  AEs = adverse events; ALT = alanine aminotransferase; AST = aspartate aminotransferase; BARI = baricitinib; CPK = creatine phosphokinase; D/C = discontinuation; ext = extended; IR = incidence rate; SAEs = serious adverse events; WBC = white blood cell.

a Data through 16-week placebo-controlled period.

b For 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. 

c p≤.05 vs BARI 2 mg.

d Includes laboratory abnormalities.

e Includes AST increased (n=3), ALT increased (n=2), blood CPK increased (n=2), neutrophil count decreased (n=2), WBC count decreased (n=2), hepatic enzyme increased (n=1), lymphocyte count abnormal (n=1), ultrasound abdomen abnormal (n=1), and weight increased (n=1).

f Benign, malignant, and unspecified, including cysts and polyps.

All Baricitinib-Treated with Extended Data

Of the 2531 patients treated with all BARI doses in the AD clinical trials, 105 (IR=4.6) had AEs leading to permanent discontinuation. Of these 105 events,

  • 35 were due to serious AEs

  • 27 were from the SOC skin and subcutaneous tissue disorders, and

  • 20 were from the SOC infections and infestations.1

See Table 1 for more details.

Death in Atopic Dermatitis Clinical Trials

Of the 2531 patients treated across all BARI doses studied in AD clinical trials, there was 1 death. The death was assessed as unrelated to study drug by the investigator.1

A 53-year-old male patient died of GI bleed while on BARI treatment for more than 12 months. The patient was randomized to receive BARI 1 mg in BREEZE-AD2 and then switched to the BARI 4 mg treatment arm in BREEZE-AD3 but received BARI 2 mg due to a GFR <60 mL/min/1.73 m2. Concomitant medications included ramipril and torasemide for hypertension and unspecified edema.1

The patient had no known risk factors for a GI bleed; however, the patient did have low erythrocytes and hematocrit levels at baseline and during the study, as well as decreased hemoglobin level 3 months prior to death.1

Integrated Safety Datasets Table

Table 2. Integrated Analysis Datasets Used to Evaluate Safety in Atopic Dermatitis Clinical Trials1

Analysis Set

Description

BARI 2 mg Placebo-Controlled

Studies: JAHG, BREEZE-AD1, BREEZE-AD2, BREEZE- AD4, BREEZE- AD5, and BREEZE-AD7

Compares BARI 2 mg vs placebo

Includes patients with AD from 1 phase 2 and 5 phase 3 studies who were randomized to

  • BARI 2 mg (n=721, PYE=210.6), or

  • placebo (n=889, PYE=252.7).

Treatment period was 0 to 16 weeks.

BARI 4 mg Placebo-Controlled

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

Compares BARI 4 mg vs placebo

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

  • BARI 4 mg (n=489, PYE=147.1), or

  • placebo (n=743, PYE=211.8).

Treatment period was 0 to 16 weeks.

BARI 2 mg vs 4 mg

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

Compares BARI 2 mg vs BARI 4 mg through 16 weeks

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), or

  • BARI 4 mg (n=489, PYE=147.1).

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

BARI 2 mg vs 4 mg Extended

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=576, PYE=425.5), or

  • BARI 4 mg (n=489, PYE=459.3).

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 AD

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

No between-group comparisons

Includes 2531 (total PYE=2247.4) 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=538, PYE=245.9)

  • BARI 2 mg (n=1580, PYE=1129.5), and

  • BARI 4 mg (n=914, PYE=872.8).

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.

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

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

Glossary

AD = atopic dermatitis

AE = adverse event

BARI = baricitinib

GFR = glomerular filtration rate

GI = gastrointestinal

SOC = system organ class

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: August 12, 2020


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