RESEARCH AND COMMENTARY - RA, interstitial lung disease, mortality and anti-TNF therapy: BSRBR

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Rheumatoid Arthritis, Interstitial Lung Disease, Mortality and

Anti-TNF Therapy: Results from the BSR Biologics Register (BSRBR) - OP

0014

Authors: Dixon, , Lunt, Hyrich, Manchester, UK

Jon Giles, M.D.

Eular 2007

Background:

Despite a high prevalence of asymptomatic pulmonary findings in RA

patients, the development of symptomatic pulmonary disease (including

interstitial lung disease (ILD)) is quite rare. Despite this rarity,

an increase in morbidity and mortality has been reported in patients

with RA-associated ILD. The safety of TNF inhibitor use in this

high-risk subgroup of RA patients was explored by Dixon et al, using

data from the British Society for Rheumatology Biologics Registry

(BSRBR).

Methods:

The BSRBR is a prospective registry of patients with rheumatic

diseases newly treated with TNF inhibitors in Britain starting in

2002. A comparison cohort of subjects not treated with TNF inhibitors

was recruited in parallel. For this analysis, mortality (linked to

the U.K. Office for National Statistics) was compared in RA patients

reporting physician-diagnosed ILD at enrollment between TNF inhibitor

treated and untreated patients, with subgroup analyses for subjects

with other extra-articular manifestations or RA and those seropositive

for rheumatoid factor (RF) using regression analysis.

Results:

9294 TNF inhibitor treated patients with RA were compared to 2454 RA

patients treated with non-biologic DMARDs with a median of between

0.92 to 2.20 person-years of follow-up. The prevalence of baseline

physician-reported ILD was higher in the TNF inhibitor treated group

compared to the non-biologic DMARD group (2.9 vs. 1.8%, respectively;

p=0.002). Patients with baseline ILD had a 3-fold higher odds of

other extra-articular manifestations of RA (OR 3.1 (95% CI 2.5 – 3.9))

and an almost 2-fold higher odds of RF seropositivity (OR 1.9 (95% CI

1.5 – 2.5)) compared to those without ILD. All cause mortality was

more than 2-fold higher in patients with baseline ILD (IRR 2.12 (95%

CI 1.52 – 2.95)).

In patients with baseline ILD, 40 of the 269 TNF inhibitor treated ILD

patients died during follow-up (14.9%) compared to 4 of the 44 non-TNF

inhibitor treated ILD patients (9.1%); p=NS. ILD was the cause of

death in 11 of the 40 death in the TNF inhibitor treated ILD patients

(27.5%) and none of the 4 non-TNF inhibitor treated ILD patients.

Conclusions:

Baseline RA-associated ILD is associated with increased mortality.

TNF inhibitor treatment may contribute to this increase.

Editorial Comment:

Pulmonary disease, particularly ILD, in RA is understudied, likely as

it is an uncommon finding. This study emphasizes the risk associated

with ILD in RA patients. The finding that 14% of the ILD patients

died in such a short follow-up period (median of about 2 years)

emphasizes the risks associated with this diagnosis. However, whether

TNF inhibitor treatment contributes to mortality is not convincingly

demonstrated by this study, as the differences in mortality (even with

the large sample size) were not significantly different according to

treatment. The numerical difference in mortality between TNF

inhibitor treated and untreated patients could be due to confounding

by indication, since the TNF inhibitor treated patients are also more

likely to have more active and severe RA (a known risk factor for

mortality in RA). Despite this, care should be taken when prescribing

biologic DMARDs to patients with advanced pulmonary disease. For

example, a link between COPD exacerbation and the use of abatacept has

been identified and TNF inhibitor treated ILD patients may have more

difficulty resisting frequent pulmonary infections.

http://www.hopkins-arthritis.org/physician-corner/education/eular2007/rheumatoid\

-arthritis-interstitial-lung-disease-mortality-and-anti-tfn-therapy.html

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