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Olumiant ® ▼ (baricitinib)
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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.3Information specific to eczema herpeticum is described in a separate response.
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
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
7 (0.3%) ophthalmic herpes simplex
1 (0.0%) herpes ophthalmic
4 (0.2%) genital herpes, and
3 (0.1%) genital herpes simplex.3
Table 1. Summary of Herpes Simplex in the Atopic Dermatitis Clinical Trials2,3
|
|
|
|
|
|
|
|
|
|
|
|
|
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 |
BARI
2 mg |
Placebo |
BARI
4 mg |
BARI
2 mg |
BARI
4 mg |
BARI
2 mg |
BARI
4 mg |
All
doses |
|
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.
Table 2. 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.
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. Published online September 14, 2020. https://doi.org/10.1111/jdv.16948
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: January 29, 2021
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