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): Incidence of Herpes Simplex in Atopic Dermatitis

Viral reactivation, including cases of herpes virus reactivation, were reported in clinical studies with baricitinib. Herpes simplex was a common (≥1% and <10%) adverse drug reaction in baricitinib clinical trials.

Baricitinib Label Information Related to Infections, Viral Reactivation and Herpes simplex

Warnings and Precautions Related to Infections

Baricitinib is associated with an increased rate of infections such as upper respiratory tract infections compared to placebo. In rheumatoid arthritis clinical studies, in treatment naïve patients, combination with methotrexate resulted in increased frequency of infections compared to baricitinib monotherapy.1

The risks and benefits of treatment with baricitinib should be carefully considered prior to initiating therapy in patients with active, chronic or recurrent infections.1

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

Warnings and Precautions Related to Viral Reactivation

Viral reactivation, including cases of herpes virus reactivation (e.g., herpes zoster, herpes simplex), were reported in clinical studies.1

Adverse Drug Reaction of Herpes simplex

Herpes simplex is a common (≥1% and <10%) adverse drug reaction with baricitinib treatment.1

The percentages of patients with atopic dermatitis reporting herpex simplex for baricitinib 4 mg compared to placebo were 6.1 % vs. 2.7 %.1

Clinical Trial Criteria

In the phase 3 AD clinical trial program, patients with symptomatic herpes simplex at time of randomization were excluded.2

Incidence of Herpes Simplex in Atopic Dermatitis Clinical Trials

Herpes simplex is a cluster of the MedDRA preferred terms of herpes simplex, oral herpes, eczema herpeticum, Kaposi's varicelliform eruption, ophthalmic herpes simplex, genital herpes, and genital herpes simplex.2 

The integrated datasets used to evaluate cases of herpes simplex are described more in Table 2.

Placebo-Controlled Period

Through 16 weeks, the proportion of patients with treatment-emergent herpes simplex was

  • not significantly different between BARI 2 mg and placebo groups

  • significantly higher in the BARI 4 mg group than the placebo group (p≤.01), and

  • significantly higher in the BARI 4 mg group than the BARI 2 mg group (p≤.05).2

All Baricitinib-Treated Patients With Extended Data

Of the 2531 patients treated across all BARI doses studied in AD, 224 (IR=10.33) had a treatment-emergent report of herpes simplex. Of the 224 reports

  • 93% were mild to moderate in severity

  • 11 (5%) were reported as serious, and

  • 5 (2%) led to permanent discontinuation of study drug.2

Among the herpes simplex cluster, the number of cases by each preferred term was

  • 110 (4.3%) oral herpes

  • 91 (3.6%) herpes simplex

  • 32 (1.3%) eczema herpeticum

  • 11 (0.4%) Kaposi's varicelliform eruption

  • 8 (0.3%) ophthalmic herpes simplex

  • 4 (0.2%) genital herpes, and

  • 3 (0.1%) genital herpes simplex.2

Table 1. Summary of Herpes Simplex in the Atopic Dermatitis Clinical Trials2

 

 

 

 

 

 

 

 

 

 

 

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]
c


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

Herpes Simplex

23 (2.8)

27 (3.8)

22 (2.7)

35 (6.1)d

25 (3.6)

35 (6.1)e

41 (5.8) [9.62]

59 (10.5) [14.47]f

224 (8.9) [10.33]

Serious AE

2 (0.2)

0

2 (0.2)

0

0

0

1 (0.1) [0.16]

3 (0.6) [0.56]

11 (0.4) [0.48]

Led to temp int

2 (0.2)

3 (0.5)

2 (0.2)

7 (1.2)g

3 (0.5)

7 (1.2)

6 (0.9) [1.37]

11 (1.9) [2.70]

39 (1.5) [1.70]

Led to perm D/C

0

0

0

0

0

0

2 (0.2) [0.32]

2 (0.4) [0.51]

5 (0.2) [0.22]

Treated with antiviral

13 (1.6)

14 (1.9)

12 (1.5)

16 (2.9)

14 (1.9)

16 (2.9)

27 (3.7) [6.12]

31 (5.7) [6.98]

131 (5.2) [5.86]

Recovered or resolved

21 (2.6)

26 (3.6)

20 (2.5)

33 (5.9)h

24 (3.4)

33 (5.9)e

38 (5.5) [9.07]

55 (9.9) [13.59]f

213 (8.4) [9.80]

Abbreviations: AD = atopic dermatitis; adj = adjusted; AE = adverse event; BARI = baricitinib; D/C = discontinuation; ext = extended; IR = incidence rate; temp int = temporary interruption.

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 Incidence rates were calculated as the number of patients with an event per 100 patient-years of exposure time, with exposure censored at time of event.

d p≤.01 vs placebo.

e p≤.05 vs BARI 2 mg.

f p≤.01 vs BARI 2 mg.

g p≤.05 vs placebo.

h p≤.001 vs placebo.

Integrated Safety Datasets

Table 2. Integrated Analysis Datasets Used to Evaluate Safety in Atopic Dermatitis Clinical Trials2

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.

Glossary

AD = atopic dermatitis

BARI = baricitinib

MedDRA = Medical Dictionary for Regulatory Activities

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: July 23, 2020


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