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): Overall and Serious Infections in Atopic Dermatitis

Baricitinib treatment is associated with an increased rate of infections.

Baricitinib Label Information Related to Infections

Warnings and Precautions

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

Adverse Drug Reactions in Atopic Dermatitis

In controlled studies, for up to 16 weeks, the incidence rate of all infections (rate of patients with ≥ 1 event per 100 patient-years of exposure) was

  • 155 with baricitinib 4 mg compared to

  • 118 in the placebo group.

Most infections were mild to moderate in severity.1

Infections were reported in 31.5 %, 29.8 % and 24.2 % of patients up to 16 weeks in the 4 mg, 2 mg and placebo groups, respectively.1

The percentage of patients reporting infection-related ADRs for baricitinib 4 mg compared to placebo were:

  • Upper respiratory tract infections (17.5 % vs. 14.1 %),

  • urinary tract infections (2.0 % vs. 0.8 %),

  • gastroenteritis (1.2 % vs. 0.5 %),

  • herpes simplex (6.1 % vs. 2.7 %),

  • herpes zoster (0 % vs. 0.3 %) and

  • pneumonia (0 % vs 0.1 %).1

In atopic dermatitis clinical studies, the frequency of infections was generally similar to those observed in rheumatoid arthritis patients except for pneumonia which was uncommon and herpes zoster which was very rare.1

There were less skin infections requiring antibiotic treatment with baricitinib 4 mg (3.4 %) than with placebo (4.4 %). 1

The same percentage of patients with serious infections was observed with baricitinib 4 mg and placebo (0.6 %). The overall incidence rate of serious infections with baricitinib in the atopic dermatitis clinical trial programme was 2.1 per 100 patient-years. 1

Atopic Dermatitis Safety Datasets

The integrated safety datasets used to evaluate infections are described in more detail in Table 4.

Infections in Atopic Dermatitis Clinical Trials

Infections were defined using MedDRA preferred terms in the infections and infestations system organ class. Infections were defined as serious infections if they met the International Conference on Harmonsation criteria for a serious AE.2

Placebo-Controlled Period

Overall Infections

Through 16 weeks, the proportion of patients with a treatment-emergent infection was

  • significantly higher in for BARI 2 mg and BARI 4 mg groups than placebo group (p values ≤.05), and

  • similar between the compared BARI 2 mg and BARI 4 mg groups (see details in Table 1).2

Serious Infections

Through 16 weeks, the proportion of patients with a treatment-emergent serious infection was not significantly different between the BARI 2 mg and BARI 4 mg groups compared to placebo groups (see Table 1).2

All Baricitinib-Treated Patients With Extended Data

Overall Infections

Of the 2531 patients treated with all BARI doses in the AD clinical trials, 1272 (IR=91.7) patients had a treatment-emergent infection. The most frequent infections reported were

  • nasopharyngitis (n=439, IR=22.0)

  • upper respiratory tract infection (n=160, IR=7.2)

  • oral herpes (n=110, IR=4.9)

  • influenza (n=100, IR=4.4)

  • herpes simplex (n=91, IR=4.0)

  • folliculitis (n=72, IR=3.2), and

  • urinary tract infection (n=72, IR=3.2).2

See Table 1 for more information including the incidence of skin infections requiring antibiotics.

Of the 137 infections that led to temporary interruption of BARI, the most frequent were HZ (n=27) and herpes simplex (n=31).2

Serious Infections

Of the infections in patients treated with BARI, 48 (IR=2.1) were considered serious. The most frequent serious infections reported were

  • eczema herpeticum (n=11, IR=0.5)

  • cellulitis (n=6, IR=0.3), and

  • pneumonia (n=3, IR=0.1).2

Table 1. Summary of Infections in the Atopic Dermatitis Clinical Trials2

 

 

 

 

 

 

 

 

 

 

 

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]
c


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

Infections

252 (28.4)

251 (34.4)d

216 (24.2)

183 (31.5)e

212 (29.8)

183 (31.5)

294 (42.5) [115.4]

281 (48.9) [117.4]f

1272 (50.3) [91.7]

Serious infections

6 (0.7)

4 (0.5)

5 (0.6)

3 (0.6)

3 (0.4)

3 (0.6)

8 (0.9) [1.5]

13 (2.5) [3.0]

48 (1.9) [2.1]

Led to temp int

6 (0.6)

17 (2.2)d

4 (0.4)

15 (2.7)g

17 (2.2)

15 (2.7)

32 (4.2) [6.8]

31 (5.6) [7.3]

137 (5.4) [6.1]

Led to perm D/C

3 (0.3)

2 (0.3)

2 (0.2)

2 (0.4)

2 (0.3)

2 (0.4)

5 (0.6) [0.9]

6 (1.2) [1.5]

20 (0.8) [0.9]

Skin infections requiring antibiotics

46 (5.4)

37 (5.5)

38 (4.4)

18 (3.4)

31 (4.8)

18 (3.4)

31 (4.8) [7.5]

18 (3.4) [4.3]

75 (3.1) [3.4]

Abbreviations: AD = atopic dermatitis; adj = adjusted; BARI = baricitinib; ext = extended IR = incidence rate; perm D/C = permanent discontinuation; 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≤.05 vs placebo

e p≤.01 vs placebo.

f p≤.01 vs BARI 2 mg.

g p≤.001 vs placebo.

Lymphopenia or Neutropenia and Infection

Baricitinib Label Information Related to Lymphocytes and Neutrophils Counts

Absolute Neutrophil Count (ANC) < 1 x 109 cells/L and Absolute Lymphocyte Count (ALC) < 0.5 x 109 cells/L were reported in less than 1 % of patients in clinical trials.1

Treatment should not be initiated, or should be temporarily interrupted, in patients with an

  • ANC < 1 x 109 cells/L, or

  • ALC < 0.5 x 109 cells/L 

observed during routine patient management.1

Association Between Infection and Neutropenia or Lymphopenia

To evaluate the association between infection and neutropenia or lymphopenia, the frequency of infections was analyzed by patient subgroups defined by the worst CTCAE grades of neutropenia and lymphopenia. For this analysis, no statistical comparison was provided. See results in Table 2 and Table 3.2

Table 2.  Treatment-Emergent Infections by Worst CTCAE Grade for Lymphopenia in Atopic Dermatitis Clinical Trials2

 

 

 

 

 

 

 

 

 

 

Lymphopenia Grades and Infection Categories

BARI 2 mg Placebo-Controlled

BARI 4 mg Placebo-Controlled

BARI 2 mg vs 4 mg

BARI 2 mg vs 4 mg ext

All BARI AD

Placebo
n=872

BARI 2 mg
n=708

Placebo
n=730

BARI 4 mg
n=487

BARI 2 mg
n=570

BARI 4 mg
n=487

BARI 2 mg
n=570

BARI 4 mg
n=487

All doses
N=2498

Patients with ≥1 TE infection
n-infection [serious]/n-Grade (adj %)
ab

Grade 0 (≥1.1 billion cells/L)

198 [3]
/694 (28.9)

192 [3]
/561 (33.2)

165 [3]
/582 (23.9)

135 [3]
/397 (28.3)

162 [2]
/453 (28.5)

135 [3]
/397 (28.3)

209 [5]
/410 (42.2)

189 [9]
/345 (46.4)

882 [33]
/1801 (49.0)

Grade 1 (<1.1 and ≥0.8 billion cells/L)

40 [1]
/140 (28.0)

46 [1]
/122 (37.8)

39 [1]
/118 (27.2)

39 [0]
/72 (46.2)

40 [1]
/101 (33.0)

39 [0]
/72 (46.2)

70 [2]
/136 (43.4)

67 [4]
/105 (53.7)

291 [10]
/545 (53.4)

Grade 2 (<0.8 and ≥0.5 billion cells/L)

14 [2]
/36 (29.1)

12 [0]
/24 (52.1)

12 [1]
/29 (24.2)

7 [0]
/15 (42.3)

9 [0]
/16 (45.8)

7 [0]
/15 (42.3)

14 [1]
/24 (55.5)

23 [0]
/33 (66.5)

89 [4]
/140 (63.6)

Grade 3 (<0.5 and ≥0.2 billion cells/L)

0/2

0/1 

0/1

2[0]
/3 (24.2)

0/0

2[0]
/3 (24.2)

0/0

2 [0]
/4 (24.2)

4 [0]
/12 (33.3)

Grade 4 (<0.2 billion cells/L)

0/0

0/0

0/0

0/0

0/0

0/0

0/0

0/0

0/0

Abbreviations: AD = atopic dermatitis; adj = adjusted; BARI = baricitinib; CTCAE = Common Terminology Criteria for Adverse Events; TE = treatment-emergent.

a All BARI AD dataset is presented as percentage, all others datasets are presented as adjusted percentage.

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. 

Table 3. Treatment-Emergent Infections by Worst CTCAE Grade for Neutropenia in Atopic Dermatitis Clinical Trials2











Neutropenia Grades and Infection Categories

BARI 2 mg Placebo-Controlled

BARI 4 mg Placebo-Controlled

BARI 2 mg vs 4 mg

BARI 2 mg vs 4 mg ext

All BARI AD

Placebo
n=872

BARI 2 mg
n=708

Placebo
n=730

BARI 4 mg
n=487

BARI 2 mg
n=570

BARI 4 mg
n=487

BARI 2 mg
n=570

BARI 4 mg
n=487

All doses
N=2498

Patients with ≥1 TE infection
n-infection [serious]/n-Grade (adj %)
ab

Grade 0 (≥2 billion cells/L)

234 [6]
/819 (28.5)

228 [3]
/645 (34.8)

201 [5]
/690 (24.2)

158 [2]
/427 (31.0)

192 [2]
/521 (29.9)

158 [2]
/427 (31.0)

260 [7]
/504 (42.7)

228 [12]
/397 (48.9)

1091 [44]
/2147 (50.8)

Grade 1 (<2 and ≥1.5 billion cells/L)

15 [0]
/44 (34.1)

18 [1]
/48 (34.8)

12 [0]
/34 (29.0)

18 [0]
/45 (29.4)

17 [1]
/41 (32.4)

18 [0]
/45 (29.4)

27 [1]
/52 (42.0)

37 [0]
/63 (48.1)

128 [1]
/254 (50.4)

Grade 2 (<1.5 and ≥1.0 billion cells/L)

3 [0]
/9 (36.0)

4 [0]
/14 (13.8)

3 [0]
/6 (36.0)

6 [1]
/14 (40.0)

2 [0]
/7 (8.9)

6 [1]
/14 (40.0)

6 [1]
/13 (33.9)

14 [1]
/24 (51.1)

44 [2]
/88 (50.0)

Grade 3 (<1.0 and ≥0.5 billion cells/L)

0/0

0/1

0/0

1 [0]
/1 (12.7)

0/0

1 [0]
/1 (12.7)

0/1

2 [0]
/3 (21.6)

3 [0]
/9 (33.3)

Grade 4 (<0.5 billion cells/L)

0/0

0/0

0/0

0/0

0/0

0/0

0/0

0/0

0/0

Abbreviations: AD = atopic dermatitis; BARI = baricitinib; CTCAE = Common Terminology Criteria for Adverse Events; TE = treatment-emergent.

a All BARI AD dataset is presented as percentage, all others datasets are presented as adjusted percentage.

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. 

Integrated Safety Datasets Table

Table 4. Integrated Analysis Datasets Used to Evaluate Safety in Atopic Dermatitis Clinical Trials2

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

Glossary

AD = atopic dermatitis

AE = adverse event

ALC = absolute lymphocyte count

ANC = absolute neutrophil count

BARI = baricitinib

CTCAE = Common Terminology Criteria for Adverse Events

HZ = herpes zoster

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: July 17, 2020


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