Baricitinib
and COVID-19
Baricitinib
is not approved for the treatment of COVID-19, COVID-19 pneumonia, or
COVID-19. Please see local labeling for approved indications.
COVID-19
Risk or Prevention in Patients with Rheumatoid Arthritis Treated with
Baricitinib
Although
BARI is being studied for the treatment of COVID-19, it is unknown if
patients treated with baricitinib for rheumatoid arthritis are at a
greater risk of both contracting COVID-19 and having COVID-19 related
complications.
Clinical
Registry Data for Patients With Rheumatological Disorders and
COVID-19
Clinical
registries have been formed to collect data from patients with
rheumatic diseases and COVID-19. These registries have assessed
baseline medications for rheumatoid arthritis as well as COVID-19
clinical outcomes.1-6
To
date, publications from these registries have reported an
insufficient volume of patients treated with JAK inhibitors,
including BARI, to draw conclusions regarding risk of contracting
COVID-19, risk for COVID-19 related complications or any potential
protective effect of JAK inhibitors.2,4-7
Risks
and Outcomes of COVID-19 in the Autoimmune Population
Analyses
on the risks and outcomes of COVID-19 in patients with autoimmune
disease, including rheumatoid arthritis, have been published.
Please see references for relevant citations.8-11
Efficacy
and Safety of Baricitinib in Patients With Rheumatoid Arthritis and
COVID-19
An
analysis of the efficacy and safety of baricitinib in patients
with RA and COVID-19 has not been conducted.
Baricitinib
Infection-Related Warnings and Precautions
COVID-19
is an active respiratory disease, which is typically mild but may
lead to acute respiratory distress syndrome which can be lethal.
Please note the important BARI infection-related warnings and
precautions listed below for consideration.
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.12
The
risks and benefits of treatment with baricitinib should be carefully
considered prior to initiating therapy in patients with active,
chronic or recurrent infections.12
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.12
Incidence
of Infections in Baricitinib Clinical trials
Upper
Respiratory Tract Infections
Upper
respiratory tract infections were very commonly (≥10%) reported
adverse events in RA BARI clinical trials.13
Table
1. Infections and Upper Respiratory Tract Infections From Rheumatoid
Arthritis Clinical Trials in the Placebo-Controlled Period13-15
|
7-Study
Dataseta
(to
Week 24)
|
n (EAIR)
|
Placebo
N=1215
PYE=450.8
|
BARI
2 mg
N=479
PYE=185.8
|
BARI
4 mg
N=1142
PYE=471.8
|
All
TE Infection
|
340
(75.4)
|
156
(84.0)
|
423
(89.7)
|
Upper
Respiratory Tract Infectionsb
|
184
(40.8)
|
91
(49.0)
|
224
(47.5)
|
Abbreviations:
BARI = baricitinib; EAIR = exposure adjusted incidence rate; IR =
incidence rate; PYE = patient-years of exposure; TE = treatment
emergent.
a
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. Patients in
the placebo group could have been taking background MTX or other
conventional DMARDs. Data from BARI 2 mg (N=479, PYE=185.8) is
derived from 4 of these studies in which both BARI 2 mg and BARI 4 mg
were options during randomization.
b
Includes acute sinusitis, epiglottitis, laryngitis,
nasopharyngitis, oropharyngeal pain, pharyngitis,
pharyngotonsillitis, rhinitis, sinusitis, sinobronchitis,
tonsillitis, tracheitis, and upper respiratory tract infection.
Serious
Infections in Rheumatoid Arthritis Clinical Trials
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, RA-BALANCE). Data
includes a long-term extension study (RA-BEYOND) with
data
through 13 February 2018
10,127
PYE, and
up
to 6.9 years of exposure.14,15
Of
the 3770 patients who received BARI in the RA clinical trials through
13 February 2018, there were 283 TE serious infections with an IR per
100 PYE, censored at time of event, of 2.8. The most frequent serious
infections reported were
pneumonia
(n=52, EAIR 0.5)
HZ
(n=35, EAIR 0.4)
urinary
tract infection (n=21, EAIR 0.2)
cellulitis
(n=15, EAIR 0.2)
sepsis
(n=18 including 14 cases of sepsis and 4 cases of urosepsis), and
gastroenteritis
(n=13, EAIR 0.13).13-15
Clinical
Factors Associated with Serious Infection
A
large group of clinical factors with the potential to affect the risk
of serious infection was evaluated using Cox models and data from the
All BARI RA dataset through 01 January 2016. The 5
independent risk factors identified for serious infection were
prior
biologic use
advanced
age
Asian
region of study enrollment, excluding Japan
non-normal
body mass index, and
concomitant
corticosteroid use.3
Additionally,
increasing grades of lymphopenia were associated with an increase in
frequency of any TE infection and serious infection in BARI-treated
patients.13
Clinical
Use
The
treating physician may use the information provided, the patient’s
prior medical history and concomitant medications, and other
individual factors, in formulating an assessment and approach. The
treating physician should consider potential risks and benefits of
treatment options, and monitor appropriately.
Infectious
Disease Resources
For
the most current information regarding COVID-19, please refer to the
WHO, ECDC and EULAR websites:
For
current NICE guidance, please refer to 'COVID-19 rapid guideline:
rheumatological autoimmune, inflammatory and metabolic bone
disorders' at www.nice.org.uk/guidance/ng167.
References
1.
Gianfrancesco M, Hyrich KL, Al-Adely S, et al. Characteristics
associated with hospitalisation for COVID-19 in people with rheumatic
disease: data from the COVID-19 Global Rheumatology Alliance
physician-reported registry. Ann Rheum Dis. Published online
May 29, 2020. http://dx.doi.org/10.1136/annrheumdis-2020-217871
2.
Gianfrancesco MA, Hyrich KL, Gossec L, et al. Rheumatic disease and
COVID-19: initial data from the COVID-19 Global Rheumatology Alliance
provider registries. Lancet Rheumatol. Published online April
16, 2020. https://doi.org/10.1016/S2665-9913(20)30095-3
3.
Winthrop KL, Genovese MC, Harigai M, et al. Serious infection and
associated risk factors in patients with moderate to severe
rheumatoid arthritis treated with baricitinib [abstract OP0248]. Ann
Rheum Dis. 2017;76(suppl 2):158.
http://ard.bmj.com/content/76/Suppl_2/158.2
4.
Scirè CA, Carrara G, Zanetti A, et al. Italian Registry of
the Italian Society for Rheumatology (CONTROL-19). COVID-19 in
rheumatic diseases in Italy: first results from the Italian registry
of the Italian Society for Rheumatology (CONTROL-19). Clin Exp
Rheumatol. 2020 Jul-Aug;38(4):748-753.
https://www.clinexprheumatol.org/article.asp?a=15906
5.
Michaud K, Wipfler K, Shaw Y, et al. Experiences of Patients With
Rheumatic Diseases in the United States During Early Days of the
COVID-19 Pandemic. ACR Open Rheumatol. 2020 Jun;2(6):335-343.
https://doi.org/10.1002/acr2.11148
6.
Hasseli R, Mueller-Ladner U, Schmeiser T, et al. National registry
for patients with inflammatory rheumatic diseases (IRD) infected with
SARS-CoV-2 in Germany (ReCoVery): a valuable mean to gain rapid and
reliable knowledge of the clinical course of SARS-CoV-2 infections in
patients with IRD. RMD Open. 2020;6:e001332.
http://dx.doi.org/10.1136/rmdopen-2020-001332
7.
Winthrop KL, Brunton AE, Beekmann S, et al. SARS CoV-2 infection
among patients using immunomodulatory therapies. Ann Rheum Dis.
Published online August 5, 2020.
http://dx.doi.org/10.1136/annrheumdis-2020-218580
8.
Freites Nuñez DD, Leon L, Mucientes A, et al. Risk factors
for hospital admissions related to COVID-19 in patients with
autoimmune inflammatory rheumatic diseases. Annals of the
Rheumatic Diseases 2020;79(11):1393-9.
https://www.doi.org/10.1136/annrheumdis-2020-217984
9.
Akiyama S, Hamdeh S, Micic D, et al. Prevalence and clinical
outcomes of COVID-19 in patients with autoimmune diseases: a systemic
review and meta-analysis. Ann Rheum Dis. 2020.
http://dx.doi.org/10.1136/annrheumdis-2020-218946
10.
Favalli EG, Monti S, Ingegnoli F, et al. Incidence of COVID-19 in
patients with rheumatic diseases treated with targeted
immunosuppressive drugs: what can we learn from observational data?
Arthritis Rheum. 2020;72(10):1600-1606.
http://dx.doi.org/10.1002/art.41388
11.
Haberman RH, Castillo R, Chen A, et al. COVID-19 in patients with
inflammatory arthritis: a prospective study on the effects of
comorbidities and DMARDs on clinical outcomes. Arthritis
Rheumatol. 2020. http://dx.doi.org/10.1002/art.41456
12.
Olumiant [summary of product characteristics]. Eli Lilly Nederland
B.V., The Netherlands.
13.
Data on file, Eli Lilly and Company and/or one of its subsidiaries.
14.
Genovese MC, Smolen JS, Takeuchi T, et al. Safety profile of
baricitinib for the treatment of rheumatoid arthritis up to 7 years:
an updated integrated safety analysis. Ann Rheum Dis.
2019;78(2):308-309.
http://dx.doi.org/10.1136/annrheumdis-2019-eular.691
15.
Genovese MC, Smolen JS, Takeuchi T, et al. Safety profile of
baricitinib for the treatment of rheumatoid arthritis up to 7 years:
an updated integrated safety analysis. Presented as an oral
presentation at: European League Against Rheumatism (EULAR) Annual
Meeting; June 12-15, 2019; Madrid, Spain.
Glossary
BARI
= baricitinib
COVID-19
= coronavirus disease 2019
EAIR
= exposure-adjusted incidence rate
ECDC
= European Center for Disease Prevention and Control
EULAR
= European League Against Rheumatism
JAK
= Janus kinase
PYE
= patient-years of exposure
RA =
rheumatoid arthritis
TE =
treatment-emergent
US =
United States
WHO
= World Health Organization
▼ 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.