Olumiant ® (baricitinib)

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Olumiant® (baricitinib): What was the incidence of gastrointestinal events in patients with atopic dermatitis?

Nausea and diverticulitis have been reported uncommonly (≥ 1/1,000 to < 1/100). Abdominal pain has been reported commonly (≥ 1/100 to < 1/10).

UK_cFAQ_BAR102B_GASTROINTESTINAL_TEAE_AD
UK_cFAQ_BAR102B_GASTROINTESTINAL_TEAE_AD
en-GB

Gastrointestinal adverse events reported in the label

Special warnings and precautions for use

Cases of diverticulitis and gastrointestinal perforation have been reported in clinical trials and from postmarketing sources.1

Baricitinib should be used with caution in patients with diverticular disease and especially in patients chronically treated with concomitant medicinal products associated with an increased risk of diverticulitis: nonsteroidal anti-inflammatory drugs, corticosteroids, and opioids.1

Patients presenting with new onset abdominal signs and symptoms should be evaluated promptly for early identification of diverticulitis or gastrointestinal perforation.1

Undesirable effects 

In atopic dermatitis clinical trials, the frequency of nausea was uncommon (≥ 1/1 000 to < 1/100).

The frequency of abdominal pain and diverticulitis, based on integrated data from clinical trials and/or postmarketing settings across rheumatoid arthritis, atopic dermatitis, and alopecia areata indications, was common (≥ 1/100 to < 1/10) and uncommon (≥ 1/1 000 to < 1/100) respectively. 1

In the integrated data from rheumatoid arthritis, atopic dermatitis and alopecia areata clinical trials, nausea was most frequent during the first 2 weeks of treatment.1

Cases or abdominal pain were usually mild, transient, not associated with infectious or inflammatory gastrointestinal disorders, and did not lead to treatment interruption.1

Gastrointestinal treatment-emergent adverse events observed in atopic dermatitis clinical trials

Based on data from clinical studies for BARI

  • nausea and abdominal pain were reported as common (≥1% and <10%) adverse drug reactions, and
  • gastrointestinal (GI) perforation is not a commonly reported treatment emergent adverse event (TEAE) with BARI treatment.2

Please find described the integrated datasets used to evaluate GI TEAEs in patients with AD described in Integrated analysis datasets used to evaluate safety in atopic dermatitis clinical trials .

Incidence of treatment-emergent gastrointestinal adverse events 

Gastrointestinal disorders system organ class treatment-emergent adverse events from the atopic dermatitis clinical program 2,3


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]


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

Gastrointestinal disorders

74 (8.4)

80 (10.9)

64 (7.3)

52 (9.2)  

60 (8.5)

52 (9.2)

81 (11.6) [19.9]

74 (13.2) [19.7]

333 (13.2) [16.1]

Nausea

11 (1.1)

19 (2.3)

8 (0.8)

4 (0.8)

14 (1.8)

4 (0.8)

16 (2.1) [3.4]

8 (1.4) [1.8]

49 (1.9) [2.1]

Diarrhoea

17 (2.0)  

16 (2.0)

15 (1.8)

15 (2.7)

10 (1.3)

15 (2.7)

15 (2.0) [3.1]

19 (3.2) [4.6]

78 (3.1) [3.5]

Abdominal pain

10 (1.3)

11 (1.5)

9 (1.2)

7 (1.3)

11 (1.5)

7 (1.3)

13 (1.9) [2.9]

7 (1.3) [1.8]

32 (1.3) [1.4]

Upper abdominal pain

11 (1.3)

11 (1.7)

10 (1.2)

14 (2.5)

10 (1.6)

14 (2.5)

14 (2.1) [3.2]

15 (2.7) [3.6]

42 (1.7) [1.8]

Lower abdominal pain

0

0

0

1 (0.2)

0

1 (0.2)

0

2 (0.4) [0.5]

2 (0.1) [0.1]

Constipation

1 (0.1)

7 (0.9)

1 (0.1)

1 (0.2)

4 (0.5)

1 (0.2)

6 (0.7) [1.1]

2 (0.4) [0.4]

22 (0.9) [1.0]

Gastritis

5 (0.5)

1 (0.2)

5 (0.5)

3 (0.5)

1 (0.2)

3 (0.5)

1 (0.2) [0.3]

6 (1.0) [1.3]

17 (0.7) [0.7]

Gastroesophageal 
reflux disease

1 (0.2)

5 (0.6)

1 (0.2)

0

2 (0.3)

0

4 (0.6) [0.8]

1 (0.2) [0.2]

16 (0.6) [0.7]

Vomiting

9 (1.0)

7 (0.9)

8 (0.9)

3 (0.6)

5 (0.7)

3 (0.6)

8 (1.2) [1.7]

3 (0.6) [0.6]

25 (1.0) [1.1]

Abbreviations: AD = atopic dermatitis; adj = adjusted; BARI = baricitinib; ext = extended; IR = incidence rate.

aData through 16-week placebo-controlled period.

bFor 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. 

The GI events reported by at least 1% of patients in either the BARI 4-mg or 2-mg group were

  • abdominal pain
  • diarrhoea
  • gastritis
  • nausea
  • upper abdominal pain, and
  • vomiting.2

Abdominal pain and nausea treatment-emergent adverse events

In the All BARI AD dataset, the majority of the abdominal pain and nausea GI-related TEAEs

Incidence of treatment-emergent abdominal pain and nausea from the atopic dermatitis clinical program 2,3

TEAE

All BARI AD Dataset
(N=2531)
[Total PYE=2247.4]

Nausea, n (%) [rate per 100 PYE]

49 (1.9) [ 2.1]

Serious cases, n

0

Led to treatment interruption, n

0

Led to permanent discontinuation, n

1

Abdominal pain, n (%) [rate per 100 PYE]

32 (1.3) [1.4]

Serious cases, n

0

Led to treatment interruption, n

1

Led to permanent discontinuation, n

2

Upper abdominal pain, n (%) [rate per 100 PYE]

42 (1.7) [1.8]

Serious cases, n

0

Led to treatment interruption, n

0

Led to permanent discontinuation, n

0

Lower abdominal pain, n (%) [rate per 100 PYE]

2 (0.1) [0.1]

Serious cases, n

0

Led to treatment interruption, n

0

Led to permanent discontinuation, n

0

Abbreviations: AD = atopic dermatitis; BARI = baricitinib; PYE = patient years of exposure; TEAE = treatment emergent adverse event.

Treatment-emergent adverse events of gastrointestinal perforations

There were no reports of GI perforations in AD clinical program.3

There were 2 reports of anal fistulas that were medically reviewed and confirmed not to be a GI perforation.2

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.

3Bieber 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

Appendix

Integrated analysis datasets used to evaluate safety in atopic dermatitis clinical trials 2,3

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.

Date of Last Review: 02 February 2021


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