Eosinophil
Counts
Absolute
eosinophil counts was part of the planned clinical laboratory tests
for the pivotal phase 3 RA trials for BARI.1
Baricitinib
Rheumatoid Arthritis Phase 3 Clinical Trial Exclusion Criteria
No
reference range for eosinophils was specified in the protocol
exclusion criterion in the pivotal phase 3 BARI trials in RA:
RA-BEAM, RA-BEACON, RA-BUILD, and RA-BEGIN. However, patients were
excluded if they had screening laboratory test values outside the
reference range for the population or investigative site that, in the
opinion of the investigator, pose an unacceptable risk for the
patient’s participation in the study.1
Incidence
of Eosinophilia or Eosinophil Count Increased in the Rheumatoid
Arthritis Clinical Development Program
Treatment-Emergent
Adverse Events
A
TEAE is an adverse event that either occurred or worsened in severity
after the first dose of study treatment and did not necessarily have
a causal relationship to study treatment.1
6-Study
Placebo-Controlled Dataset
Description
The
6-study placebo-controlled dataset compared BARI 4 mg vs placebo and
included patients with RA who were randomized to BARI 4 mg (N=997) or
placebo (N=1070) from 3 phase 2 and 3 phase 3 studies. In the
majority of the studies, patients were on background therapy either
with MTX or another csDMARD. The BARI 2-mg data is derived from 4
studies in which both BARI 2 mg (N=479) and BARI 4 mg were options
during randomization.2
Difference
in Eosinophil Counts
At
endpoint (up to 16 weeks), a smaller proportion of patients in the
BARI 4-mg group had abnormal high eosinophil counts vs placebo (Table
1).1
Table
1. Changes in Eosinophil Counts in the Baricitinib 4 mg Rheumatoid
Arthritis Placebo-Controlled Trials Up to 16 Weeks1
Eosinophils
(Billion Cells/L)
|
Baseline,
Mean (SD)
|
Change
From Baseline, LSM (SE)
|
Change
From Baseline (95% CI)
|
Difference
in LSM Between BARI 4-mg and PBO for Change From Baseline
|
BARI
4 mg (n=997)
|
0.144
(0.142)
|
-0.038
(0.0045)
|
(-0.047,
-0.029)
|
-0.042a
|
PBO
(n=1068)
|
0.136
(0.12)
|
0.004
(0.0043)
|
(-0.004,
0.012)
|
--
|
Abbreviations:
BARI = baricitinib; LSM = least squares mean; PBO = placebo.
a
p≤.05.
7-Study
Placebo-Controlled Dataset
Description
The
7-study pooled dataset included patients with RA randomized to BARI 4
mg (N=1142, PYE=471.8) or placebo (N=1215, PYE=450.8) from 3 phase 2
studies and 4 phase 3 studies (RA-BEAM, RA-BUILD, RA-BEACON, and
RA-BALANCE). Patients could have been taking background MTX or other
conventional DMARDs. Evaluation time periods included through
the
12-week placebo-controlled period in phase 2 studies
16
weeks of assigned treatment before any opportunity for rescue
therapy in phase 3 studies, and
24
weeks of assigned treatment or until rescue in phase 3 studies.3
Data
from BARI 2 mg (N=479, PYE=185.8) were derived from 4 of these
studies in which both BARI 2 mg and BARI 4 mg were options during
randomization (2 phase 2 studies as well as RA-BUILD and RA-BEACON).3
Incidence
of Eosinophilia or Eosinophil Count Increased in the 7-Study Placebo
Controlled Analysis Set
In
this safety analysis, through 24 weeks of treatment, TEAEs of
eosinophil count increased and eosinophilia are shown in Table
2.
Table
2. Incidence of Eosinophilia/Eosinophil Count Increased in the BARI
Safety Analysis, Through 24 Weeks
n
(%) [EAIR]
|
BARI
4 mg (n=1142)
|
BARI
2 mg (n=479)
|
PBO
(n=1215)
|
Eosinophil
count increased
|
0
|
0
|
2
(0.2) [0.4]
|
Eosinophilia
|
3
(0.3) [0.6]
|
1
(0.2) [0.5]
|
1
(0.1) [0.2]
|
Abbreviations:
BARI = baricitinib; EAIR = exposure-adjusted incidence rate; PBO =
placebo.
All
Baricitinib Rheumatoid Arthritis Analysis Dataset
Description
The
All BARI RA analysis set included 3770 patients with RA who received
BARI at a variety of doses from 1 phase 1, 3 phase 2, and 5 phase 3
studies (RA-BEGIN, RA-BEAM, RA-BUILD, RA-BEACON, and RA-BALANCE).
Data includes a long-term extension study (RA-BEYOND) with
13,148
PYE
median
exposure of 4.2 years
maximum
exposure of 8.4 years, and
data
through September 1, 2019.4,5
Incidence
of Eosinophilia or Eosinophil Count Increased in the All Baricitinib
Rheumatoid Arthritis Analysis Set
In
the All BARI RA analysis set through September 1, 2019, a TEAE of
eosinophilia or eosinophil count increased was reported in 24
patients.1
None
of the 24 TEAEs of eosinophilia or eosinophil count increased were
reported as serious. For more information on events, see Table
3.1
Table
3. Incidence of Eosinophilia or Eosinophil Count Increased in the All
BARI RA Analysis Set1
n
(%) [EAIR]
|
TEAE
|
Temporary
Interruption
|
Permanent
Discontinuation
|
Eosinophilia
|
16
(0.4) [0.1]
|
1
(0.0) [0.0]
|
1
(0.0) [0.0]
|
Eosinophil
count increased
|
8
(0.2) [0.1]
|
0
|
0
|
Abbreviations:
EAIR = exposure-adjusted incidence rate; TEAE = treatment-emergent
adverse event.
References
1.
Data on file, Eli Lilly and Company and/or one of its subsidiaries.
2.
Smolen JS, Genovese MC, Takeuchi T, et al. Safety profile of
baricitinib in patients with active rheumatoid arthritis with over 2
years median time in treatment. J Rheumatol. 2019;46(1):7-18.
http://dx.doi.org/10.3899/jrheum.171361
3.
Genovese MC, Smolen JS, Takeuchi T, et al. Safety profile of
baricitinib for the treatment of rheumatoid arthritis over a median
of 3 years of treatment: an updated integrated safety analysis.
Lancet Rheumatol. 2020;2(6):E347-E357.
https://doi.org/10.1016/S2665-9913(20)30032-1
4.
Genovese MC, Smolen JS, Takeuchi T, et al. Safety profile of
baricitinib for the treatment of rheumatoid arthritis up to 8.4
years: an updated integrated safety analysis [abstract]. Ann Rheum
Dis. 2020;79(suppl 1):638.
https://ard.bmj.com/content/79/Suppl_1/642.1
5.
Genovese MC, Smolen JS, Takeuchi T, et al. Safety profile of
baricitinib for the treatment of rheumatoid arthritis up to 8.4
years: an updated integrated safety analysis. Poster presented at:
European League Against Rheumatism Virtual Congress; June 3-6, 2020.
Glossary
BARI
= baricitinib
csDMARD
= conventional synthetic disease-modifying antirheumatic drug
DMARD
= disease-modifying antirheumatic drug
MTX
= methotrexate
PYE
= patient-years of exposure
RA =
rheumatoid arthritis
TEAE
= treatment-emergent adverse event
▼ 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.