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): Herpes Zoster in Atopic Dermatitis

Viral reactivation, including cases of herpes virus reactivation, were reported in clinical studies with baricitinib. If a patient develops herpes zoster, baricitinib treatment should be interrupted until the episode resolves.

Baricitinib Label Information Related to Herpes Zoster

Warnings and Precautions Related Viral Reactivation

Viral reactivation, including cases of herpes virus reactivation (e.g., herpes zoster, herpes simplex), were reported in clinical studies. In rheumatoid arthritis clinical studies, herpes zoster was reported more commonly in patients ≥ 65 years of age who had previously been treated with both biologic and conventional DMARDs.1

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

Warnings and Precautions Related to Vaccination

No data are available on the response to vaccination with live vaccines in patients receiving baricitinib. Use with live, attenuated vaccines during, or immediately prior to, baricitinib therapy is not recommended.1

Prior to initiating baricitinib, it is recommended that all patients be brought up to date with all immunisations in agreement with current immunisation guidelines.1

No studies have been conducted on the use of BARI with a non-live HZ vaccine, therefore no information is available.

Adverse Drug Reaction of Herpes Zoster

Herpes zoster is a common adverse drug reaction (≥ 1/100 to < 1/10) with baricitinib treatment. Frequency for herpes zoster is based on rheumatoid arthritis clinical trials.1

In patients treated with baricitinib in the atopic dermatitis clinical trials, the frequency of herpes zoster was very rare (< 1/10,000).1

The percentage of patients with atopic dermatitis reporting herpes zoster for baricitinib 4 mg compared to placebo were 0 % vs. 0.3 %.1

Clinical Trial Protocol Information Related to Herpes Zoster

Clinical Trial Exclusion Criteria Related to Herpes Zoster

Live vaccines, including HZ vaccination, were prohibited during the phase 3 studies of BARI for the treatment of AD. Patients were excluded from the studies if they

  • were exposed to HZ vaccination within 4 weeks of planned randomization

  • had symptomatic HZ infection within 12 weeks prior to study entry, or

  • had history of disseminated or complicated HZ, defined as

    • multidermatomal involvement

    • ophthalmic zoster

    • central nervous system involvement, or

    • postherpetic neuralgia.2,3

In the phase 3 clinical trials, patients were encouraged to receive a HZ vaccine, if eligible based on local guidelines, at least 4 weeks prior to randomization.3

Herpes Zoster During Clinical Trials

During the clinical trials, if a patient developed symptomatic HZ, investigators were instructed to

  • interrupt study treatment, and

  • resume study treatment when all skin lesions had crusted and resolved.3

Herpes Zoster in Atopic Dermatitis Clinical Trials

The integrated datasets used to evaluate cases of HZ are described in more detail in Table 1.

Prior Herpes Zoster and Vaccination in Baricitinib-Treated Patients

Of the 2531 patients treated across all BARI doses studied in AD

  • 116 (4.6%) had a prior case of HZ, and

  • 112 (4.8%) had received the HZ vaccine.3

Treatment-Emergent Herpes Zoster

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.3

Placebo-Controlled Period

Through the 16-week placebo-controlled period, the proportion of patients with treatment-emergent HZ was not significantly different between the BARI 2 mg and BARI 4 mg groups compared to placebo group. There were more HZ cases in the BARI 2 mg group than the BARI 4 mg (p≤.05).2,3 Table 1 provides more details on HZ in the AD clinical trials for all integrated safety datasets.

All Baricitinib-Treated Patients With Extended Data

Of the 2531 patients treated across all BARI doses studied in AD, 53 (IR=2.3) had a treatment-emergent case of HZ. Of the 53 HZ events

  • 96% of cases were mild to moderate in severity

  • 0 were reported as SAEs

  • 3 cases were multidermatomal, and

  • 1 case was disseminated.2,3

See Table 1 for more details.

Table 1. Summary of Herpes Zoster in the Atopic Dermatitis Clinical Trials2,3

 

 

 

 

 

 

 

 

 

 

 

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

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

BARI 2 vs 4a
n (adj %)
b

BARI 2 vs 4 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

Herpes Zoster

3 (0.3)

6 (0.8)

3 (0.3)

0

6 (0.8)c

0

16 (2.5) [3.8]

8 (1.5) [1.8]

53 (2.1) [2.3]

Serious AE

0

0

0

0

0

0

0

0

0

Led to temp int

1 (0.1)

5 (0.7)

1 (0.1)

0

5 (0.7)c

0

8 (1.3) [1.9]

5 (1.0) [1.1]

27 (1.1) [1.2]

Led to perm D/C

0

0

0

0

0

0

0

0

1 (0.0) [0.0]

Treated w/ antiviral

2 (0.2)

4 (0.6)

2 (0.2)

0

4 (0.6)

0

13 (2.2) [3.2]

8 (1.5) [1.8]

43 (1.7) [1.8]

Recovered or resolved

2 (0.2)

5 (0.6)

2 (0.2)

0

5 (0.6)c

0

15 (2.3) [3.5]

7 (1.3) [1.5]

50 (2.0) [2.2]

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

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 AEs to provide appropriate direct comparisons between treatment groups. 

c p≤.05 vs BARI 4 mg.

Integrated Safety Analysis Datasets

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.

References

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

2. 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

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

Glossary

AD = atopic dermatitis

BARI = baricitinib

HZ = herpes zoster

IR = incidence rate

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 22, 2021


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