Treatment of rheumatoid arthritis-associated interstitial lung disease: a perspective review

Abstract

Rheumatoid arthritis (RA) is a systemic autoimmune disease affecting 0.5-1% of the worldwide population. Whilst predominantly causing chronic pain and inflammation in synovial joints, it is also associated with significant extra-articular manifestations in a large proportion of patients. Among the various pulmonary manifestations, interstitial lung disease (ILD), a progressive fibrotic disease of the lung parenchyma, is the commonest and most important, contributing significantly to increased morbidity and mortality. The most frequent patterns of RA-associated ILD (RA-ILD) are usual interstitial pneumonia and nonspecific interstitial pneumonia. New insights during the past several years have highlighted the epidemiological impact of RA-ILD and have begun to identify factors contributing to its pathogenesis. Risk factors include smoking, male sex, human leukocyte antigen haplotype, rheumatoid factor and anticyclic citrullinated protein antibodies (ACPAs). Combined with clinical information, chest examination and pulmonary function testing, high-resolution computed tomography of the chest forms the basis of investigation and allows assessment of subtype and disease extent. The management of RA-ILD is a challenge. Several therapeutic agents have been suggested in the literature but as yet no large randomized controlled trials have been undertaken to guide clinical management. Therapy is further complicated by commonly prescribed drugs of proven articular benefit such as methotrexate, leflunomide (LEF) and anti-tumour necrosis factor α agents having been implicated in both ex novo occurrence and acceleration of existing ILD. Agents that offer promise include immunomodulators such as mycophenolate and rituximab as well as newly studied antifibrotic agents. In this review, we discuss the current literature to evaluate recommendations for the management of RA-ILD and discuss key gaps in our knowledge of this important disease.

Factors influencing the choice of first- and second-line biologic therapy for the treatment of rheumatoid arthritis: real-life data from the Italian LORHEN Registry

“…The presence of a concomitant pulmonary condition was associated with a relative risk (RR) of 2.19 (95% CI: 1.05-2.4) of choosing ABA compared to TNFi. Unfortunately, the nature of this registry study does not allow to explore this finding in deeper detail, but it may be speculated that interstitial lung disease (ILD) might represent the main underlying pulmonary comorbidities leading to the choice of ABA over TNFi [26,27]. Another possible explanation could regard the infectious risk.…”

Mortality in patients with interstitial lung disease treated with rituximab or TNFi as a first biologic

“…Though different from a typical cohort of patients with RA starting a biologic, those included in this analysis were reflective of patients with RA-ILD, 14 increasing the external validity of these findings. Unfortunately, data regarding the subtype or severity of the underlying RA-ILD, which have been associated with differences in mortality, were not available.…”

“…9 However, ILD has been reported as a complication of treatment in lymphoma patients treated with RTX 10 11 and less is known regarding the outcomes and mortality risk in patients with RA-ILD who receive RTX. [12][13][14] Previous analyses within the British Society for Rheumatology Biologics Register for RA (BSRBR-RA) 15 reported no significant difference in mortality rates between patients with RA-ILD treated with TNFi or csDMARDs. However, a greater proportion of deaths were attributed to RA-ILD in the TNFi cohort.…”

Rituximab therapy in interstitial lung disease associated with rheumatoid arthritis

“…Solomon et al . and Iqbal and Kelly emphasised that often RA‐ILD patients present an isolated early alteration of DLCO with normal lung volumes.…”

“…The principal symptoms associated with RA‐ILD are exertional dyspnoea and dry cough, however, a variable percentage of patients ranging from 30 to 90% are asymptomatic or show mild symptoms . A restrictive pattern at pulmonary function tests (PFT) with reduced diffusing capacity of the lung for carbon monoxide (DLCO) percentages are the most frequent functional alterations . Radiological patterns at high‐resolution computed tomography (HRCT), can be usual interstitial pneumonia (UIP), non‐specific interstitial pneumonia (NSIP), diffuse alveolar damage (DAD), lymphocytic interstitial pneumonia (LIP) and bronchiolitis obliterans organising pneumonia (BOOP).…”