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): Interruption of Treatment due to Safety in the Atopic Dermatitis Clinical Trials

In the atopic dermatitis clinical trials with baricitinb, the majority of temporary treatment interruptions were due to adverse events, with infections being the most common adverse events.

Baricitinib Label Information Related to Treatment Interruption

Recommendations Regarding Baricitinib Treatment Interruption

If an infection develops, the patient should be monitored carefully and baricitinib therapy should be temporarily interrupted if the patient is not responding to standard therapy. Baricitinib treatment should not be resumed until the infection resolves.1

If a patient develops herpes zoster, baricitinib treatment should be temporarily interrupted until the episode resolves.1

If clinical features of DVT/PE occur, baricitinib treatment should be discontinued and patients should be evaluated promptly, followed by appropriate treatment.1

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

  • ANC < 1 x 109 cells/L,

  • ALC < 0.5 x 109 cells/L or

  • haemoglobin < 8 g/dL

observed during routine patient management.1

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.1

Individuals of Reproductive Potential 

Baricitinib is contraindicated during pregnancy. Women of childbearing potential have to use effective contraception during and for at least 1 week after treatment.1

If a patient becomes pregnant while taking baricitinib the parents should be informed of the potential risk to the foetus.1

Clinical Decision

The treating physician may use the information provided, the patient’s medical information, clinical presentation, and other individual factors in formulating an assessment and approach for individual treatment interruption and restart of therapy. The treating physician should consider potential risks and benefits and use their best clinical judgment regarding treatment.

Temporary Interruption of Treatment in Atopic Dermatitis Clinical Trials

The integrated datasets used to evaluate temporary treatment interruptions are described in detail in Table 3.

Overall Treatment Interruptions

Table 1 presents an overview of temporary interruptions including reasons for interruption and duration of interruptions across the integrated datasets.

Table 1. Overview of Temporary Interruption of Treatment From Atopic Dermatitis Clinical Trials2

 

BARI 2 mg Placebo-Controlleda 

BARI 4 mg Placebo-Controlleda

BARI 2 mg vs 4 mga

BARI 2 mg vs 4 mg Ext

All BARI AD


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)

Total treatment interruptions, n

35

35

30

33

31

33

65

86

345

Resumed study treatment, n

30

28

25

30

26

30

54

73

301

2 interruptions, n

2

4

2

1

4

1

8

14

48

Reasons for interruption, n (% of N)

AEb

19 (2.1)

27 (3.7)

16 (2.2)

25 (5.1)

25 (4.3)

25 (5.1)

48 (8.3)

54 (11.0)

229 (9.0)

Abnormal lab result

7 (0.8)

3 (0.4)

5 (0.7)

3 (0.6)

2 (0.3)

3 (0.6)

2 (0.3)

9 (1.8)

27 (1.1)

Protocolc

3 (0.3)

0

3 (0.4)

0

0

0

4 (0.7)

2 (0.4)

9 (0.4)

Suspected pregnancy

0

0

0

0

0

0

1 (0.2)

0

1 (0.0)

Investigator decision

4 (0.4)

0

4 (0.5)

0

0

0

1 (0.2)

4 (0.8)

13 (0.5)

Missing

0

1 (0.1)

0

1 (0.2)

0

1 (0.2)

0

1 (0.2)

3 (0.1)

Time to first interruption, days

Mean (SD)

40.1 (29.6)

50.6 (36.7)

40.5 (31.7)

49.2 (40.0)

49.7 (34.3)

49.2 (40.0)

134.2 (110.6)

180.4 (149.1)

166.0 (140.4)

Median

41.0

37.0

37.5

34.0

37.0

34.0

114.5

141.5

135.5

Duration of interruption, days

Mean (SD)

12.2 (9.9)

12.4 (12.3)

11.6 (7.8)

10.0 (5.9)

11.9 (11.9)

10.0 (5.9)

14.2 (14.7)

17.6 (35.4)

15.0 (22.3)

Median

10.0

7.5

10.0

8.0

7.5

8.0

8.5

9.0

9.0

Abbreviations: AD = atopic dermatitis; AE = adverse events; BARI = baricitinib; ext = extended.

a Data through 16-week placebo-controlled period.

b Include all AEs that led to interruption.

c Criteria for temporary interruption of study drug were included in all study protocols. Some of these criteria may not have led to reports of AEs or abnormal laboratory findings.

Placebo-Controlled Period

Through 16 weeks, the results were similar between the BARI 2 mg, BARI 4 mg, and placebo groups in

  • number of treatment interruptions

  • median time to first interruption, and

  • mean duration of interruption.2

Adverse events were the most common reason for temporary interruption across all treatment groups.2

All Baricitinib-Treated Patients With Extended Data

Of the 2531 patients treated across all BARI doses studied in AD clinical trial, there were 345 total treatment interruptions. The majority of patients only had 1 treatment interruption and resumed treatment after the interruption.2

The most common reasons for temporary interruption were AEs, which resulted in 229 treatment interruptions.2,3

Treatment Interruptions Due to Adverse Events 

Adverse events leading to temporary treatment interruption by MedDRA SOC are presented in Table 2.

Table 2. Adverse Events Leading to Temporary Interruption of Treatment by System Organ Class2,3

 

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 treatment interruptionc

18 (2.0)

28 (3.5)

14 (1.6)

26 (4.6)d

27 (3.4)

26 (4.6)

47 (6.3) [10.4]

54 (9.7) [12.7]e

218 (8.6) [9.9]

Infections and infestations

6 (0.6)

17 (2.2)f

4 (0.4)

15 (2.7)g

17 (2.2)

15 (2.7)

32 (4.2) [6.8]

31 (5.6) [7.3]

137 (5.4) [6.1]h

Skin and subcutaneous tissue disorders

0

2 (0.2)

0

3 (0.6)f

2 (0.2)

3 (0.6)

4 (0.6) [0.9]

5 (1.0) [1.2]

16 (0.6) [0.7]i

Investigationsj

3 (0.3)

3 (0.3)

2 (0.2)

2 (0.4)

3 (0.3)

2 (0.4)

4 (0.5) [0.8]

5 (0.9) [1.1]

14 (0.6) [0.6]k

Respiratory, thoracic and mediastinal disorders

2 (0.3)

1 (0.1)

1 (0.2)

2 (0.3)

1 (0.1)

2 (0.3)

1 (0.1) [0.2]

3 (0.5) [0.7]

12 (0.5) [0.5]

Gastrointestinal disorders

3 (0.3)

3 (0.5)

3 (0.3)

0

3 (0.5)

0

3 (0.5) [0.7]

0

8 (0.3) [0.3]

Nervous system disorders

1 (0.1)

1 (0.1)

1 (0.1)

1 (0.1)

1 (0.1)

1 (0.1)

2 (0.2) [0.4]

2 (0.3) [0.4]

8 (0.3) [0.3]

Injury, poisoning and procedural complications

0

2 (0.2)

0

1 (0.2)

1 (0.1)

1 (0.2)

1 (0.1) [0.2]

1 (0.2) [0.2]

6 (0.2) [0.3]

Blood and lymphatic system disorders

1 (0.1)

0

1 (0.1)

1 (0.2)

0

1 (0.2)

0

2 (0.4) [0.5]

5 (0.2) [0.2]

Surgical and medical procedures

0

0

0

0

0

0

0

0

4 (0.2) [0.2]

Cardiac disorders

0

0

0

0

0

0

0

0

3 (0.1) [0.1]

Eye disorders

1 (0.1)

0

1 (0.1)

1 (0.1)

0

1 (0.1)

0

2 (0.3) [0.4]

3 (0.1) [0.1]

Ear and labyrinth disorders

0

0

0

0

0

0

0

1 (0.2) [0.2]

2 (0.1) [0.1]

General disorders and administration site conditions

0

0

0

0

0

0

0

0

2 (0.1) [0.1]

Hepatobiliary disorders

0

0

0

0

0

0

0

2 (0.4) [0.4]

2 (0.1) [0.1]

Musculoskeletal and connective tissue disorders

1 (0.1)

1 (0.0)

1 (0.1)

0

0

0

0

0

2 (0.1) [0.1]

Psychiatric disorders

1 (0.1)

1 (0.1)

1 (0.1)

0

1 (0.1)

0

1 (0.1) [0.2]

0

2 (0.1) [0.1]

Renal and urinary disorders

0

0

0

1 (0.2)

0

1 (0.2)

0

1 (0.2) [0.2]

2 (0.1) [0.1]

Vascular disorders

0

0

0

0

0

0

1 (0.2) [0.3]

1 (0.2) [0.2]

2 (0.1) [0.1]

Neoplasms benign, malignant, and unspecified

1 (0.1)

0

1 (0.1)

0

0

0

0

0

1 (0.0) [0.0]

Abbreviations: AD = atopic dermatitis; adj = adjusted; AEs = adverse events; ALT = alanine aminotransferase; BARI = baricitinib; CPK = creatine phosphokinase; ext = extended; IR = incidence rate; LFT = liver function tests.

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 (eg, 2:1:1:1 vs 1:1:1:1), the study-size adjusted percentages were calculated for the AEs to provide appropriate direct comparisons between treatment groups. 

c Include AEs which led to interruption after first dose date but at or before the interruption date.

d p≤.01 vs placebo.

e p≤.05 vs BARI 2 mg.

f p ≤.05 vs placebo.

g p≤.001 vs placebo.

h Most frequent include: herpes zoster (n=27), herpes simplex (n=18), eczema herpeticum (n=13), and cellulitis (n=8).

i Most frequent include: atopic dermatitis (n=3), blister (n=2), dyshidrotic eczema (n=2), and toxic skin eruption (n=2).

j Includes abnormal laboratory findings.

k Includes: CPK increased (n=5), ALT increased (n=3), neutrophil decreased (n=2), hepatic enzyme increased (n=1), LFT increased (n=1), lymphocyte decreased (n=1), and biopsy (n=1).

Placebo-Controlled Period

Through 16 weeks, compared to placebo, there was a significantly greater number of 

  • treatment interruptions due to AEs in the BARI 4 mg group, and

  • interruptions due to infections and infestations SOC in both the BARI 2 mg and BARI 4 mg groups.2

There was no significant difference in treatment interruptions by individual infection preferred terms between BARI treatments and placebo groups.2

All Baricitinib-Treated Patients With Extended Data

In the All BARI AD dataset, AEs in the infections and infestations SOC were the most common cause for treatment interruptions. Herpes zoster (n=27) and herpes simplex (n=18) were the most frequent infections causing temporary interruptions.2,3

Impact of Temporary Treatment Interruption on Efficacy and Safety

Analyses on the impact of temporary treatment interruption on efficacy and safety of BARI therapy in AD have not been conducted, therefore no information is available.

Integrated Safety Analysis Datasets

Table 3. Integrated Analysis Datasets Used to Evaluate Safety in Atopic Dermatitis Clinical Trials2,3

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

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

3. Bieber 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

Glossary

AD = atopic dermatitis

AE = adverse event

BARI = baricitinib

MedDRA = Medical Dictionary for Regulatory Activities

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: February 01, 2021


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