Olumiant ® (baricitinib)

This information is intended for UK registered healthcare professionals only as a scientific exchange in response to your search for information.For current prescribing information for all Lilly products, including Summaries of Product Characteristics, Patient Information Leaflets and Instructions for Use, please visit: www.medicines.org.uk (England, Scotland, Wales) or www.emcmedicines.com/en-GB/northernireland/ (Northern Ireland).

What is the incidence of infections with baricitinib treatment in the alopecia areata clinical development program?

Upper respiratory tract infection, nasopharyngitis, and urinary tract infection were common TEAEs observed in baricitinib-treated patients with alopecia areata. Most infections were mild or moderate in severity and serious infections were uncommon.

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Information from the label 

Baricitinib is associated with an increased rate of infections such as upper respiratory tract infections compared to placebo. In rheumatoid arthritis clinical studies, 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 therapy should be temporarily interrupted if the patient is not responding to standard therapy. Treatment should not be resumed until the infection resolves.1

Absolute Neutrophil Count (ANC) < 1 x 109 cells/L, Absolute Lymphocyte Count (ALC) < 0.5 x 109 cells/L, and haemoglobin < 8 g/dL were reported in clinical trials.1

Treatment should not be initiated in patients with

  • an absolute lymphocyte count (ALC) less than 0.5 x 109 cells/L,
  • an absolute neutrophil count (ANC) less than 1 x 109 cells/L, or who have
  • a haemoglobin value less than 8 g/dL.1

Treatment may be initiated once values have improved above these limits.1

Patients should be screened for tuberculosis (TB) before starting therapy.1

  • Baricitinib should not be given to patients with active TB.1
  • Anti-TB therapy should be considered prior to initiation of treatment in patients with previously untreated latent TB.1

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 (HZ) was reported more commonly in patients ≥ 65 years of age who had previously been treated with both biologic and conventional disease-modifying antirheumatic drugs (DMARDs).1

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

Screening for viral hepatitis should be performed in accordance with clinical guidelines before starting therapy with baricitinib.1

  • Patients with evidence of active hepatitis B or C infection were excluded from clinical trials.
  • Patients, who were positive for hepatitis C antibody but negative for hepatitis C virus RNA, were allowed to participate.
  • Patients with hepatitis B surface antibody and hepatitis B core antibody, without hepatitis B surface antigen, were also allowed to participate; such patients should be monitored for expression of hepatitis B virus (HBV) DNA.
  • If HBV DNA is detected, a liver specialist should be consulted to determine if treatment interruption is warranted.

Infections in Alopecia Areata Clinical Trials

The baricitinib alopecia areata (AA) clinical trial program includes

The incidence of infections in the BRAVE-AA trials was reported in 3 integrated safety datasets, including the

  • 36-week placebo-controlled BARI AA dataset with patients exposed to placebo, baricitinib 2 mg, and baricitinib 4 mg from randomization to week 36
  • extended BARI AA dataset with patients exposed to baricitinib 2 mg or 4 mg from randomization to dose or treatment change, or data cutoff, and
  • All-BARI-AA dataset with all patients exposed to any baricitinib dose (1-mg, 2-mg, or 4-mg) at any time during the studies.5

Safety data were integrated from the BRAVE-AA1 phase 2 and 3 cohorts (data cutoff March 31, 2021) and from BRAVE-AA2 (data cutoff March 24, 2021).5

More details on patient exposure and censoring rules in each dataset are provided in Integrated Analysis Datasets Used to Evaluate Safety in Alopecia Areata Clinical Trials .

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.

Across the baricitinib AA analysis sets,

  • most infections were of mild or moderate severity
  • herpes zoster was the most reported event term that led to temporary interruption of study drug as mandated in the protocol, all patients recovered, and
  • no opportunistic infections were reported.6

See Summary of Infections in the Alopecia Areata Clinical Trials for a summary of infections in the AA clinical trials and Treatment-Emergent Adverse Events in the Infections and Infestations System Organ Class Occurring in ≥1% of Baricitinib-Treated Patients in the Alopecia Areata Clinical Trials for treatment-emergent (TE) infections reported in ≥1% of baricitinib-treated patients. Upper respiratory tract infection, nasopharyngitis, and urinary tract infection were the most common TE infections observed in baricitinib-treated patients with AA.6

Summary of Infections in the Alopecia Areata Clinical Trials5,6

 

36-Week Placebo-Controlled Period

Extended BARI AA

All BARI AA

 

Placebo
N=371
PYE=243.2

BARI 2 mg
N=365
PYE=240.6

BARI 4 mg
N=540
PYE=363.4

BARI 2 mg
N=365
PYE=371.5

BARI 4 mg
N=540
PYE=624.3

All Doses
N=1244
PYE=1362.2


n (%) [IR]

n [IR]

Patients with ≥1 TEAEa

108 (29.1)
[55.5]

118 (32.3)
[62.9]

165 (30.6)
[57.3]

145
[52.8]

216
[47.3]

458
[46.4]

Serious AE

0

2 (0.5)
[0.8]

1 (0.2)
[0.3]

2
[0.5]

4
[0.6]

9
[0.6]

  Pyelonephritis

0

1 (0.3)
[0.4]

1 (0.2)
[0.3]

1
[0.3]

1
[0.2]

2
[0.1]

  COVID-19 pneumonia 

0

1 (0.3)
[0.4]

0

1
[0.3]

0

2
[0.1]

  COVID-19b 

0

0

0

0

1
[0.2]

2
[0.1]

  Diverticulitis

0

0

0

0

1
[0.2]

1
[0.1 

  Herpes zoster

0

0

0

0

1
[0.2]

1
[0.1]

  Varicella

0

0

0

0

0

1
[0.1]

Led to temporary interruption

10 (2.7)
[4.1]

12 (3.3)
[5.0]

11 (2.0)
[3.0]

14
[3.7]

21
[3.3]

51
[3.7]

Led to permanent discontinuation

0

1 (0.3)
[0.4]

0

1
[0.3]

1
[0.2]

2c
[0.1]

Abbreviations: AA = alopecia areata; AE = adverse event; BARI = baricitinib; IR = incidence rate; PYE = patient-years of exposure; TEAE = treatment-emergent adverse event.

Note: IRs are calculated based on patient-years at risk.

aThe most frequently reported infection terms in BARI-treated patients were upper respiratory tract infection, nasopharyngitis, and urinary tract infection.

b‘SARS-CoV-2 test positive’ term in placebo-controlled period was recoded to ‘COVID-19’ for the Extended and All BARI analysis sets.

c1 event of lower respiratory tract infection and 1 event of COVID-19.

Treatment-Emergent Adverse Events in the Infections and Infestations System Organ Class Occurring in ≥1% of Baricitinib-Treated Patients in the Alopecia Areata Clinical Trials6

 

36-Week Placebo-Controlled Period

Extended BARI AA

All BARI AA

 

Placebo
N=371
PYE=243.2

BARI 2 mg
N=365
PYE=240.6

BARI 4 mg
N=540
PYE=363.4

BARI 2 mg
N=365
PYE=371.5

BARI 4 mg
N=540
PYE=624.3

All Doses
N=1244
PYE=1362.2

Preferred Term

n (%) [IR]

n (%) [IR]

Upper respiratory tract infection

26 (7.0)
[11.2]

24 (6.6)
[10.3]

41 (7.6)
[11.8]

33 (9.0)
[9.0]

51 (9.4)
[8.5]

101 (8.1)
[7.8]

Nasopharyngitis

19 (5.1)
[8.0]

16 (4.4)
[6.8]

37 (6.9)
[10.7]

22 (6.0)
[5.8]

44 (8.1)
[7.3]

77 (6.2)
[5.8]

Urinary tract infection

6 (1.6)
[2.5]

14 (3.8)
[5.9]

18 (3.3)
[5.0]

19 (5.2)
[5.0]

26 (4.8)
[4.1]

57 (4.6)
[4.2]

Influenza

7 (1.9)
[2.9]

6 (1.6)
[2.5]

14 (2.6)
[3.9]

7 (1.9)
[1.8]

16 (3.0)
[2.5]

25 (2.0)
[1.8]

Folliculitis

3 (0.8)
[1.2]

5 (1.4)
[2.1]

12 (2.2)
[3.3]

6 (1.6)
[1.5]

15 (2.8)
[2.4]

30 (2.4)
[2.2]

Viral upper respiratory tract infection

6 (1.6)
[2.5]

8 (2.2)
[3.4]

8 (1.5)
[2.2]

8 (2.2)
[2.1]

10 (1.9)
[1.6]

20 (1.6)
[1.5]

Oral herpes

9 (2.4)
[3.7]

6 (1.6)
[2.5]

7 (1.3)
[1.9]

7 (1.9)
[1.8]

13 (2.4)
[2.0

25 (2.0)
[1.8]

Bronchitis

1 (0.3)
[0.4]

3 (0.8)
[1.2]

6 (1.1)
[1.7]

3 (0.8)
[0.8]

7 (1.3)
[1.1]

12 (1.0)
[0.9]

Herpes zoster

2 (0.5)
[0.8]

5 (1.4)
[2.1]

5 (0.9)
[1.4]

7 (1.9)
[1.8]

9 (1.7)
[1.4]

20 (1.6)
[1.4]

Sinusitis

6 (1.6)
[2.5]

4 (1.1)
[1.7]

5 (0.9)
[1.4]

7 (1.9)
[1.8]

10 (1.9)
[1.6]

21 (1.7)
[1.5]

Gastroenteritis

6 (1.6)
[2.5]

6 (1.6)
[2.5]

4 (0.7)
[1.1]

8 (2.2)
[2.1]

5 (0.9)
[0.8]

18 (1.4)
[1.3]

Vulvovaginal candidiasisa

0

6 (2.6)
[4.0]

4 (1.2)
[1.8]

6 (2.6)
[2.4]

6 (1.8)
[1.5]

16 (2.1)
[1.9]

COVID-19

2 (0.5)
[0.8]

1 (0.3)
[0.4]

1 (0.2)
[0.3]

5 (1.4)
[1.3]

18 (3.3)
[2.8]

44 (3.5)
[3.2]

Pharyngitis

2 (0.5)
[0.8]

3 (0.8)
[1.2]

5 (0.9)
[1.4]

3 (0.8)
[0.8]

8 (1.5)
[1.2]

13 (1.0)
[0.9]

Gastroenteritis viral

1 (0.3)
[0.4]

1 (0.3)
[0.4]

4 (0.7)
[1.1]

2 (0.5)
[0.5]

6 (1.1)
[0.9]

11 (0.9)
[0.8]

Hordeolum

1 (0.3)
[0.4]

3 (0.8)
[1.2]

2 (0.4)
[0.5]

4 (1.1)
[1.0]

3 (0.6)
[0.5]

11 (0.9)
[0.8]

Otitis externa

1 (0.3)
[0.4]

2 (0.5)
[0.8]

1 (0.2)
[0.3]

4 (1.1)
[1.0]

2 (0.4)
[0.3]

7 (0.6)
[0.5]

Tooth infection

0

3 (0.8)
[1.2]

1 (0.2)
[0.3]

4 (1.1)
[1.0]

1 (0.2)
[0.2]

5 (0.4)
[0.4]

Vaginal infectiona

0

2 (0.9)
[1.3]

1 (0.3)
[0.4]

3 (1.3)
[1.2]

1 (0.3)
[0.2]

4 (0.5)
[0.5]

Abbreviations: AA = alopecia areata; BARI = baricitinib; COVID-19 = coronavirus disease 2019; IR = incidence rate; PYE = patient-years of exposure.

Note: IRs are calculated based on patient-years at risk.

aDenominator and patient years adjusted because event is specific to females: N=222 (placebo), N=223 (BARI 2-mg), N=333 (BARI 4-mg).

36-Week Placebo-Controlled Period

During the 36-week placebo-controlled period,

  • a similar proportion of patients reported TE infections in baricitinib and placebo groups
  • no dose-related differences were observed, and
  • no patients in the placebo group and 3 patients in the baricitinib groups reported serious infections.6

Extended BARI AA Analysis Set

In the extended BARI AA analysis set, the incidence rates of TE infections in the baricitinib 2-mg and baricitinib 4-mg groups were similar or lower compared to the respective dose group in the placebo-controlled period.6

Urinary Tract infections

36-Week Placebo-Controlled Period

In the 36-week placebo-controlled period, TE urinary tract infections were more frequent in the baricitinib 2-mg (3.8%) and baricitinib 4-mg (3.3%) groups compared with placebo (1.6%). Differences between baricitinib and placebo were not significant.6

Of the 38 patients who reported a TE urinary tract infection in the placebo, baricitinib 2 mg and 4 mg groups, 37 were female patients and 1 was male.6

Baricitinib treatment is associated with an increased rate of infections and urinary tract infections have been recognized as an adverse drug reaction in the established safety profile of baricitinib.6

All BARI AA Analysis Set

In the All BARI AA dataset, TE urinary tract infections were reported in 57 patients. None of the reported events of urinary tract infections were serious, or led to treatment interruption or permanent discontinuation of study drug.6

Clinical Trial Protocol Information Related to Infections

Clinical Trial Exclusion Criteria Related to Infections

Patients were excluded from the AA clinical trials if they had a current or recent and/or serious viral, bacterial, fungal, or parasitic infection, including but not limited to

  • clinically serious infection, or received intravenous antibiotics for an infection within 4 weeks before randomization, or
  • any other active or recent infection within 4 weeks of randomization that, in the opinion of the investigator, would pose an unacceptable risk to the patient if participating in the study.6

A recent viral upper respiratory tract infection or uncomplicated urinary tract infection was not considered clinically serious.6

Infections During Clinical Trials

Infections were defined using preferred terms from the Medical Dictionary for Regulatory Activities infections and infestations system organ class.6

Serious infections were defined as all infections that met the International Conference of Harmonisation serious adverse event criteria.6

If a patient developed an infection,

  • investigators could temporarily interrupt investigational product if merited, and
  • resume the investigational product when the infection is resolved.6

References

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

2King B, Ohyama M, Kwon O, et al; BRAVE-AA investigators. Two phase 3 trials of baricitinib for alopecia areata. N Engl J Med. 2022;386(18):1687-1699. https://doi.org/10.1056/nejmoa2110343

3A study of baricitinib (LY3009104) in adults with severe or very severe alopecia areata (BRAVE-AA2). ClinicalTrials.gov identifier: NCT03899259. Updated January 26, 2022. Accessed March 4, 2022. https://clinicaltrials.gov/ct2/show/NCT03899259

4A study of baricitinib (LY3009104) in participants with severe or very severe alopecia areata (BRAVE-AA1). ClinicalTrials.gov identifier: NCT03570749. Updated February 3, 2022. Accessed March 4, 2022. https://clinicaltrials.gov/ct2/show/study/NCT03570749

5King B, Mostaghimi A, Shimomura Y, et al. Integrated safety analysis of baricitinib in adults with severe alopecia areata from two randomized clinical trials. Poster presented at: Annual Meeting of the American Academy of Dermatology Association (AAD); March 25-29, 2022; Boston, MA. Accessed April 29, 2022. https://aad-eposters.s3.amazonaws.com/AM2022/poster/33966/Integrated+safety+analysis+of+baricitinib+in+adults+with+severe+alopecia+areata+from+two+randomized+clinical+trials.pdf

6Data on file, Eli Lilly and Company and/or one of its subsidiaries.

Integrated Safety Datasets Table

Integrated Analysis Datasets Used to Evaluate Safety in Alopecia Areata Clinical Trials5,6 

Analysis Set

Description

36-Week placebo-controlled BARI AA

Assesses BARI 4 mg, BARI 2 mg, and placebo.

Includes patients from the phase 2/3 BRAVE-AA1 and phase 3 BRAVE-AA2 studies who were randomized to

  • BARI 4 mg (n=540, PYE=363.4)
  • BARI 2 mg (n=365, PYE=240.6), or
  • placebo (n=371, PYE=243.2).

Evaluation time period included randomization to week 36.

Extended BARI AA

Assesses BARI 4 mg and BARI 2 mg including extended evaluations.

Includes patients from the phase 2/3 BRAVE-AA1 and phase 3 BRAVE-AA2 studies who were randomized to

  • BARI 4 mg (n=540, PYE=624.3), or
  • BARI 2 mg (n=365, PYE=371.5).

Evaluation time period included randomization up to data cutoff, March 24, 2021 for BRAVE-AA2 and March 31, 2021 for BRAVE-AA1. Data were censored after a patient was switched to another dose or treatment.

All BARI AA

No between-group assessments.

Includes 1244 (total PYE=1362.2) patients from the phase 2/3 BRAVE-AA1 and phase 3 BRAVE-AA2 studies who were exposed to any BARI dose, including

  • BARI 4 mg (n=938, PYE=858.9)
  • BARI 2 mg (n=564, PYE=488.9), or
  • BARI 1 mg (n=28, PYE=14.6).

Evaluation time period included any time points during the studies either from randomization or from switch or rescue from placebo.

Abbreviations: AA = alopecia areata; BARI = baricitinib; PYE = patient-years of exposure.

Date of Last Review: 13 June 2022


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