Olumiant ® (baricitinib)

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What is the incidence rate of herpes zoster with Olumiant® (baricitinib) treatment for atopic dermatitis?

The incidence of HZ was 127 (IR=2.8) in the 2636 patients treated with BARI for AD up to 3.9 years. Viral reactivation (including HZ) was reported in clinical studies. If a patient develops HZ, treatment should be interrupted until the episode resolves.

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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, treatment should be temporarily interrupted until the episode resolves.1

Adverse Drug Reaction of Herpes Zoster

Frequency of herpes zoster was very rare (<1/10,000) in atopic dermatitis. 

    The frequency is based on integrated data from1

    • clinical trials and/or
    • postmarketing setting.

    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 Integrated Analysis Datasets Used to Evaluate Safety in Atopic Dermatitis Clinical Trials.

    Prior Herpes Zoster and Vaccination in Baricitinib-Treated Patients

    Of the 2636 patients treated across all baricitinib doses studied in atopic dermatitis (AD)

    • 118 (4.5%) had a prior case of HZ, and
    • 124 (4.7%) 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 higher in the baricitinib 2 mg group than the baricitinib 4 mg and placebo groups.2Summary of Herpes Zoster in the Atopic Dermatitis Clinical Trials provides more details on HZ in the AD clinical trials for all integrated safety datasets.

    All Baricitinib-Treated Patients With Extended Data

    Of the 2636 patients treated across all baricitinib doses studied in AD, 127 (IR=2.8) had a treatment-emergent case of HZ. Of the 127 HZ events

    • 95% of cases were mild to moderate in severity
    • 2 were reported as serious adverse events (SAEs)
    • 6 cases were multidermatomal, and
    • 5 case was disseminated.3,4

    See Summary of Herpes Zoster in the Atopic Dermatitis Clinical Trials for more details.

    Summary of Herpes Zoster in the Atopic Dermatitis Clinical Trials3,4

     

    Placebo-Controlled
    (to Week 16)
    n (adj%) [adj IR]a

    BARI 2 mg and 4 mg Extended
    (up to 3.9 years)
    n [adj IR]a

    All BARI AD
    (up to 3.9 years)
    n [IR]

     

    Placebo
    n=743
    PYE=211.8

    BARI 2 mg
    n=576
    PYE=169.1

    BARI 4 mg
    N=489
    PYE=147.1

    BARI 2 mg
    n=584
    PYE=727.1

    BARI 4 mg 
    n=497
    PYE=800.1

    All Doses
    N=2636
    PYE=4628.4

    Herpes Zoster clusterb

    3 (0.3) [1.0]

    6 (0.8) [2.7]

    0

    23 [3.2]

    22 [3.0]

    127 [2.8]

    Serious AE

    0

    0

    0

    1 [0.2]

    0

    2 [0.0]

    Led to temp int

    1 (0.1)

    5 (0.7)

    0

    13 [1.9]

    12 [1.6]

    80 [1.7]

    Led to perm D/C

    0

    0

    0

    0

    1 [0.2]

    3 [0.1]

    Treated w/ antiviral

    2 (0.2)

    4 (0.6)

    0

    20 [2.9]

    18 [2.5]

    100 [2.2]

    Recovered or resolved

    2 (0.2)

    5 (0.6)

    0

    22 [3.1]

    21 [2.8]

    119 [2.6]

    Abbreviations: AD = atopic dermatitis; adj = adjusted; AE = adverse event; BARI = baricitinib; IR = incidence rate; MedDRA = Medical Dictionary for Regulatory Activities; perm D/C = permanent discontinued; PYE = patient-years of exposure; temp int = temporary interruption; w/ = with.

    aFor 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.

    bHerpes zoster cluster includes MedDRA preferred terms of herpes zoster, herpes zosters disseminated, opthalmic herpes zoster, and varicella zoster virus infection.

    Integrated Safety Analysis Datasets

    Integrated Analysis Datasets Used to Evaluate Safety in Atopic Dermatitis Clinical Trials2-5

    Analysis Set

    Description

    16-Week Placebo-Controlled BARI AD

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

    Compares BARI 2 mg, BARI 4 mg and placebo.

    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)
    • BARI 4 mg (n=489, PYE=147.1), or
    • placebo (n=743, PYE=211.8).

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

    BARI 2 mg and 4 mg Extended ADa

    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=584, PYE=727.1), or
    • BARI 4 mg (n=497, PYE=800.1).

    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-AD6a

    No between-group comparisons

    Includes 2636 (total PYE=4628.4) 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=605, PYE=441.5)
    • BARI 2 mg (n=1703, PYE=2420.9), and
    • BARI 4 mg (n=1012, PYE=1766.8).

    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.

    aData cut as of November 3, 2021 for BREEZE-AD3 and December 15, 2021 for BREEZE-AD4

    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

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

    2Bieber 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

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

    4Bieber T, Katoh N, Simpson EL, et al. Safety of baricitinib for the treatment of atopic dermatitis over a median of 1.6 and up to 3.9 years treatment: an updated integrated analysis of 8 clinical trials. Poster presented at: 31st Annual European Academy of Dermatology and Venereology Congress; September 7-10, 2022; Milan, Italy.

    5King B, Maari C, Lain E, et al. Extended safety analysis of baricitinib 2 mg in adult patients with atopic dermatitis: an integrated analysis from eight randomized clinical trials. Am J Clin Dermatol. 2021;22(3):395-405. https://doi.org/10.1007/s40257-021-00602-x

    Date of Last Review: 22 September 2022


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