Olumiant ® (baricitinib)

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Olumiant® (baricitinib): What was the incidence of hypersensitivity in atopic dermatitis clinical trials?

In the 2636 patients treated with baricitinib for atopic dermatitis up to 3.9 years, the incidence rate per 100 patient-years at risk was 1.8 for rash, 1.0 for urticaria, and 0.4 for swelling of the face.

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Baricitinib Label Information Related to Hypersensitivity

Contraindications, Warnings and Precautions

Baricitinib is contraindicated in case of hypersensitivity to the active substance or to any of the excipients.1

In post-marketing experience, cases of hypersensitivity associated with baricitinib administration have been reported.1

If any serious allergic or anaphylactic reaction occurs, treatment should be discontinued immediately.1

Adverse Drug Reactions: Rash, Urticaria, and Swelling of the Face 

Rash, urticaria, and swelling of the face have been reported in postmarketing spontaneous reports and are identified adverse drug reactions (ADRs) associated with baricitinib therapy.2

Rash was reported as a common event (≥1% and <10%) with baricitinib. Urticaria and swelling of the face were reported as uncommon events (≥0.1% and <1%).1,2

Clinical Trial Criteria Related to Hypersensitivity

In the atopic dermatitis (AD) clinical trials, baricitinib was not to be used in patients with hypersensitivity to the active substance or to any of its excipients.2

Allergic Reactions and Hypersensitivities in the Baricitinib Atopic Dermatitis Clinical Trials

In the AD trials, data were reported in 3 integrated safety datasets as described in Integrated Analysis Datasets Used to Evaluate Safety in Atopic Dermatitis Clinical Trials.

Hypersensitivity events in the AD trials were identified using the Standardized Medical Dictionary for Regulatory Activities Queries (SMQs) of

  • hypersensitivity
  • angioedema, and
  • anaphylactic reaction.2,3

The incidence of hypersensitivity events by SMQ and other hypersensitivity events of interest are provided in Hypersensitivity Events and Hypersensitivity Events of Special Interest in the Baricitinib Atopic Dermatitis Trials.

    Hypersensitivity Events and Hypersensitivity Events of Special Interest in the Baricitinib Atopic Dermatitis Trials2,4

     

    Placebo-Controlled
    (to week 16)
    n (adj %)a

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

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

    Placebo
    n=743

    BARI 2 mg
    n=576

    BARI 4 mg
    n=489

    BARI 2 mg
    n=584

    BARI 4 mg
    n=497

    All doses
    N=2636

    Hypersensitivityb

    46 (5.1)

    38 (5.5)

    30 (5.0)

    65 (9.3) [9.5]

    76 (12.3) [10.4]c 

    326 [7.5]

    Angioedemab

    8 (0.9)

    7 (0.9)

    5 (1.0)

    15 (2.1) [2.0]

    22 (3.6) [2.9]

    80 [1.7]

    Anaphylactic reactionb

    0

    0

    0

    1 (0.2) [0.2]

    0

    4 [0.1]d 

    Urticariae

    4 (0.5)

    3 (0.4)

    2 (0.4)

    7 (1.0) [0.9]

    12 (2.0) [1.6]

    45 [1.0]

    Rashf

    12 (1.2)

    9 (1.3)

    8 (1.3)

    17 (2.5) [2.4]

    19 (3.2) [2.5] 

    81 [1.8]

    Face Swellingg

    3 (0.3)

    4 (0.5)

    3 (0.6)

    4 (0.5) [0.5]

    6 (0.9) [0.7]

    18 [0.4]

    Abbreviations: AD = atopic dermatitis; adj = adjusted; BARI = baricitinib; IR = incidence rate; MedDRA = Medical Dictionary for Regulatory Activities; SMQ = standardized MedDRA query.

    Note: For a complete list of the preferred terms under each SMQ (narrow), please visit the BioPortal from the National Center for Biomedical Ontology. Note that some preferred terms within each SMQ are duplicated, as the 3 SMQs are not mutually exclusive and contain overlapping terms.2 

    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 adverse events to provide appropriate direct comparisons between treatment groups.

    bEvents identified using the SMQs of Hypersensitivity, Angioedema, or Anaphylactic Reaction (narrow search).

    cp<.05 for BARI 4 mg vs BARI 2 mg.

    dIncluded 3 cases of anaphylactic reactions and 1 case of anaphylactic shock.

    eBased on individual MedDRA preferred term.

    fBased on a cluster of related MedDRA preferred terms including rash, dermatitis, dermatitis contact, eczema, dermatitis allergic, rash maculo-papular, rash pruritic, rash pustular, drug eruption, rash erythematous, rash macular, rash papular.

    gBased on a cluster of related MedDRA preferred terms including swelling face, lip swelling, eye swelling, swelling of eyelid, face oedema, mouth swelling.

    Placebo-Controlled Period

    In the 16-week placebo-controlled period, there was no significant difference in the frequency of hypersensitivity and angioedema events between the baricitinib 4 mg or 2 mg compared to placebo groups (Hypersensitivity Events and Hypersensitivity Events of Special Interest in the Baricitinib Atopic Dermatitis Trials).2 

    No events of anaphylactic reaction were reported.2

    The frequency of urticaria, rash, and swelling of the face was also not significantly different between the baricitinib 4 mg or 2 mg compared to placebo groups.2

    All Baricitinib-Treated Patients With Extended Period

    In the Extended period, the adjusted incidence rate (adj IR) of hypersensitivity events was significantly greater in the baricitinib 4 mg vs 2 mg groups (adj IR=10.4 vs 9.5; p<.05; see Hypersensitivity Events and Hypersensitivity Events of Special Interest in the Baricitinib Atopic Dermatitis Trials).

    Among the 2636 patients in the All BARI AD dataset, hypersensitivity events reported by more than 1% were

    • dermatitis atopic (n=52, 2.0%)
    • conjunctivitis allergic (n=49, 1.9%)
    • urticaria (n=45, 1.7%), and
    • dermatitis contact (n=36, 1.4%).2

    In the All BARI AD dataset, 3 cases of anaphylactic reactions and 1 case of anaphylactic shock were reported. One anaphylactic reaction was reported as serious and led to temporary interruption of baricitinib. One case of anaphylactic shock by dairy ingestion was reported in a patient with food allergy. This event was not considered serious and did not lead to temporary interruption or discontinuation of baricitinib.2

    Of the 45 cases of urticaria reported in the All BARI AD dataset, 1 was considered a serious and 3 led to temporary interruption of baricitinib.2

    In the All BARI AD dataset, no patients reported an event of swelling of the face that was considered serious or led to treatment interruption or discontinuation.2

    Risk of Allergic Reactions and Hypersensitivities in Patients With Atopic Dermatitis

    Patients with AD have an increased risk of general allergic reactions, including food and airborne allergens. The risk of developing allergies is related to the epidermal permeability barrier defect and a genetic predisposition in patients with elevated serum immunoglobulin (ig) E and allergen-specific Ig E, facilitating allergen sensitization.5 

    Integrated Safety Datasets Table

    Integrated Analysis Datasets Used to Evaluate Safety in Atopic Dermatitis Clinical Trials2,4,6,7

    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.

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

    3Mozzicato P. Standardised MedDRA Queries. Drug-Safety. 2007;30:617–619. https://doi.org/10.2165/00002018-200730070-00009

    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.

    5Tham EH, Leung DY. Mechanisms by which atopic dermatitis predisposes to food allergy and the atopic march. Allergy Asthma Immunol Res. 2019;11(1):4-15. https://doi.org/10.4168/aair.2019.11.1.4

    6Bieber 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

    7King 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: 01 September 2022


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