We have certainly changed the course of RA, and have improved the severity of the disease. At the same time, there are many extraarticular manifestations of the disease that we used to see but rarely ever encounter today. For instance, we rarely see Felty’s syndrome, which is associated with seropositive RA and is characterized by the classic triad of RA, splenomegaly, and granulocytopenia. In addition, we do not see rheumatoid nodules as frequently today, and we rarely see episcleritis or rheumatoid vasculitis.

Patients today are healthier and do not have as much baseline damage when they become enrolled in randomized controlled trials because they have been treated with methotrexate or even leflunomide. The best predictor of structural progression is baseline damage, and today we see that patients with RA have had less structural damage, so the risk for additional structural progression is reduced. We are also seeing far fewer small joint replacements and articular surgeries in patients with RA, although I do not believe that the rates of hip or knee replacements have changed significantly.

However, we are seeing more ILD, along with many of the drivers of RA, itself, as either a comorbidity or a predictor of those people who will go on to develop seropositive, anti–citrullinated protein antibody (ACPA)–positive RA. I believe that ILD has been underrecognized in the past and is a condition we are now recognizing much more frequently. This is, at least in part, due to increased detection using modern imaging techniques.

Although the incidence of clinically significant RA-associated ILD is relatively low, its presence portends approximately 3-fold the risk for mortality compared with RA and no ILD. Additionally, approximately one-third of patients have subclinical RA-associated ILD with varying degrees of functional impairment.

Pathophysiologically, it is known that lung inflammation occurs at the earliest stages of RA. Parenchymal changes and citrullinated proteins have been identified in the lungs of patients with early ACPA-positive RA. Data from the SERA (Scottish Early Rheumatoid Arthritis) cohort study have demonstrated the presence of antibodies against acetylated vimentin in the sera of patients with early RA. Further, ILD may precede the development of RA, which underscores the importance of monitoring ILD patients for signs and symptoms of arthritis. However, we really lack the data at this point to help us understand how best to treat RA-associated ILD. Of course, we need to control the underlying RA as best as we are able, but the ILD may progress regardless, leading to declines in function and early mortality. RA-associated ILD responds to glucocorticoid therapy, however steroid-sparing immunosuppressive agents are often necessitated. In such cases, I would avoid methotrexate, and, based primarily on experience in Systemic Sclerosis-associated ILD, mycophenolate mofetil offers the best alternative.