Incidence
of Interstitial Lung Disease in Rheumatoid Arthritis
Depending
on the study population, the prevalence of clinically significant ILD
among RA patients has been reported to range between 5% to 30% or
higher.1-3
Interstitial
lung disease is a relatively common extra-articular manifestation of
RA with subclinical interstitial lung abnormalities detected in 30%
to 50% of RA patients.1,2
In
addition to being a relatively common complication of RA, ILD confers
a higher risk of mortality.2-4
Interstitial
Lung Disease and Pulmonary Fibrosis in the Rheumatoid Arthritis
Clinical Development Program
Description
of the All BARI RA Dataset
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
13,148
PYE,
median
exposure of 4.2 years,
maximum
exposure of 8.4 years, and
data
through 01 September 2019.5,6
Incidence
of Interstitial Lung Disease in the All BARI RA Dataset
In
the All BARI RA dataset, the MedDRA PT, ILD, was reported as a TEAE
in 17 patients treated with BARI (0.5%; 0.1 EAIR); an EAIR of 0.1 per
100 PYE for patients treated with BARI is consistent with the
background rate of ILD in patients with RA.7
Interstitial
Lung Disease Events Leading to Temporary Interruption, Permanent
Discontinuation, or Considered Serious
Of
the 17 reported TEAEs of ILD, 13 patients had events that led to
temporary interruption, permanent discontinuation, or were classified
as SAE (see Table 1).7
Table
1. Incidence of Interstitial Lung Disease in the All BARI RA Safety
Dataset7
|
TEAE
n
(EAIR)
|
Treatment
Interruption
n (EAIR)
|
Permanent
Study Discontinuation
n (EAIR)
|
SAE
n
(EAIR)
|
All
BARI RA (N=3770)
|
17
(0.1)
|
1
(0.0)
|
9
(0.1)
|
6
(0.05)
|
Abbreviations:
BARI = baricitinib; EAIR = exposure-adjusted incidence rate; RA
= rheumatoid arthritis; SAE = serious adverse event; TEAE = treatment
emergent adverse event.
Exposure-adjusted
incidence rates were calculated as the number of patients with an
event per 100 patient-years of exposure time, with exposure not
censored at time of event.
Past
Medical History
Three
patients had a past medical history of ILD. One patient experienced
an event >100 days after starting BARI.7
Confounding
Variables
Ten
patients were taking methotrexate concomitantly. Additionally, 2 of
the patients reported smoking cigarettes.7
Resolution
of Event
For
the 7 patients who were hospitalized for ILD the event was considered
resolved after hospitalization. Five patients were treated with
antibiotics for pneumonia based on imaging or presentation with
fever. Three patients had worsening cases, which resolved after
antibiotics or hospitalization.7
Three
patients that reported ILD adverse events died after hospitalization
due to
ILD
acute
respiratory failure, and
lung
infection.7
Incidence
of Pulmonary Fibrosis in the All BARI RA Dataset
In
the All BARI RA dataset, the MedDRA PT, pulmonary fibrosis, was
reported as a TEAE in 5 patients treated with BARI (0.1%; 0 EAIR).
None of these events was considered a SAE, and none of these events
led to temporary or permanent discontinuation of study drug.7
Information
from the Label
Interstitial
lung disease is not listed among the adverse events listed in the
summary of product characteristics.8
References
1.
Brito Y, Glassberg MK, Ascherman DP. Rheumatoid arthritis-associated
interstitial lung disease: Current concepts. Curr Rheumatol Rep.
2017;19(12):79. https://dx.doi.org/10.1007/s11926-017-0701-5
2.
Hyldgaard C, Hilberg O, et al. A population-based cohort study of
rheumatoid arthritis-associated interstitial lung disease:
comorbidity and mortality. Ann Rheum Dis.
2017;76(10):1700-1706.
https://dx.doi.org/10.1136/annrheumdis-2017-211138
3.
Bongartz T, Nannini C, et al. Incidence and mortality of
interstitial lungdisease in rheumatoid arthritis: a population-based
study. Arthritis Rheum. 2010;62(6):1583-1591.
https://dx.doi.org/10.1002/art.27405
4.
Zamora-Legoff JA, Krause ML, et al. Patterns of interstitial lung
disease and mortality in rheumatoid arthritis. Rheumatology
(Oxford). 2017;56(3):344-350.
https://dx.doi.org/10.1093/rheumatology/kew391
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 [abstract]. Ann Rheum
Dis. 2020;79(suppl 1):638.
https://ard.bmj.com/content/79/Suppl_1/642.1
6.
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.
7.
Data on file, Eli Lilly and Company and/or one of its subsidiaries.
8.
Olumiant [summary of product characteristics]. Eli Lilly Nederland
B.V., The Netherlands.
Glossary
BARI
= baricitinib
EAIR
= exposure-adjusted incidence rate
ILD
= interstitial lung disease
MedDRA
= Medical Dictionary for Regulatory Activities
PT =
preferred term
PYE
= patient-years of exposure
RA =
rheumatoid arthritis
SAE
= serious adverse event
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.