Rheumatoid arthritis (RA) is a common autoimmune condition characterised by symmetrical inflammatory small joint polyarthropathy and loss of function. Systemic manifestations of RA including interstitial lung disease (ILD) are relatively common and thought to occur in up to 40% of patients [
1]. ILD is associated with significant increase in morbidity and mortality in RA compared to patients who do not have ILD [
2,
3]. ILD can have different patterns and the classification (and prognosis) of ILD is based on findings on the basis of radiological patterns as seen on computed tomography (CT) scans with the subtypes being usual interstitial pneumonia (UIP), non-specific interstitial pneumonia (NSIP), organising pneumonia (OP), desquamative interstitial pneumonia (DIP), respiratory bronchiolitis (RB-ILD) and diffuse alveolar damage (DAD) [
4]. Apart from RA and other autoimmune conditions, ILD may be associated with exposure to inorganic or organic particles or to drugs. When no such association occurs, it is known as idiopathic interstitial pneumonia [
5]. In 2000, following data showing an especially poor prognosis amongst patients with IIP with the pulmonary histopathology of usual interstitial pneumonia (UIP), idiopathic pulmonary fibrosis (IPF) were specifically defined as IIP with a UIP pattern on biopsy [
6]. Over the following years, international consensus statements have refined the radiological appearances allowing a diagnosis of IPF without biopsy [
7]. IPF has a very poor prognosis, with median survival of 3–5 years [
6]. Whereas immunosuppression is widely used to treat RA and other autoimmune conditions, triple therapy with Prednisolone, azathioprine and N-acetyl cysteine was found to increase mortality in IPF [
8]. This led to the development of antifibrotic agents such as pirfenidone [
9] and nintedanib [
10] which have been shown to reduce the rate of decline in forced vital capacity (FVC) in IPF and have become the standard of care [
11].
There is some evidence to suggest improvement in mortality trends in rheumatoid arthritis-associated ILD (RA-ILD) over the last couple of decades and data from the Early Rheumatoid Arthritis Network (ERAN) suggest a better prognosis compared to previous datasets [
12,
13]. There are also studies supporting a better prognosis for RA-ILD compared to IPF [
14,
15]. UIP pattern is typically seen in both conditions whilst idiopathic interstitial pneumonia that is not IPF (IIP–not IPF) also has a better prognosis [
6,
16].
Although ILD is well recognised in patients with RA, it is often picked up due to minor symptoms or on screening examinations [
17]. Very few studies have directly compared RA-ILD with IPF, and there remains uncertainty about whether survival benefits correlate with pathophysiology [
18]. Some recent studies have looked at progression in RA-ILD and a study on ‘early’ IPF showed slower rates of progression compared to more established disease [
19,
20]. Historically there were no specific treatments for RA-ILD and recently antifibrotic drugs have been studied. The TRAIL1 study which directly examined pirfenidone vs placebo in RA-ILD closed recruitment prematurely due to the COVID-19 pandemic and its primary endpoint was negative, although a secondary endpoint suggested pirfenidone may have some efficacy at slowing FVC decline in RA-ILD [
21]. RA-ILD was also one of the disease categories comprising ‘progressive fibrosing ILD’ (PFILD) in the INBUILD study [
22,
23] and showed that nintedanib slowed FVC decline in these subjects.
To investigate differences between RA-ILD and IPF, we decided to conduct this study based on routinely collected historical data from University Hospital Coventry and Warwickshire NHS Trust (UHCW) for patients with ILD. Since antifibrotics were only available for IPF, we were concerned about the bias this would introduce. Hence, we decided to restrict the inclusion prior to the widespread use of antifibrotics in ILD care (pirfenidone was the first antifibrotic and this became available within National Health Service (NHS) following the National Institute for Health and Care Excellence Technology Appraisal (NICE TA) in 2013) [
24] and compared baseline demographics, clinical and survival data.