A Rheumatologist & Pulmonologist Discuss RA-ILD

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Introduction

The understanding and treatment of rheuma­toid arthritis (RA) has evolved dramatically in the past 20 years. As gains have been made in treating joint disease in RA, our understanding of the impact of extra-articular manifestations of RA, such as cardiac and lung disease—specifically interstitial lung disease (ILD)—has gradually increased.

While rheumatologists increasingly appreciate the impact of ILD in their patients with RA and that treatment strategies are now emerging, they have found it challenging to incorporate screening strategies into their clinical practice given the lack of guidance from either rheumatology or pul­monary societies. In their article in Rheuma­tology, Joshua Solomon, MD, of the Division of Pulmonary, Critical Care and Sleep Medicine at National Jewish Health, Denver, and Paul Dellaripa, MD, of the Division of Rheumatology, Brigham and Women’s Hospital, Boston, provide insights into our present understanding of this life-threatening complication based on a worldwide survey of practicing rheumatologists and pulmonologists they conducted.¹

In this lively dialogue, Drs Solomon and Dellaripa share the results of their study and discuss some of their thoughts on strategies going forward that may aid clinicians in the identification and treatment of patients with RA-ILD.

The Conversation

Paul: Josh, it’s such a treat today to shoot the breeze on a topic near and dear to both of us, RA-ILD. As you know, RA-ILD lived in the shadows of clinical care in RA for years, given our focus on controlling joint inflammation. But studies have shown that pulmonary complications in RA have a substantial impact on our patients in terms of quality of life and mortality.

Josh: Paul, I agree, RA-ILD was relegated to secondary consideration as rheuma­tologists struggled to gain success with articular disease, and now the range of therapeutic options available for articular RA is astonishing. As someone who specializes in ILD, I am honestly quite jealous. However, while patients have better control of their joint disease, we have begun to realize that a segment of these patients have underlying respiratory problems, like ILD and emphysema, and it turns out that it is a not a minor complication.

RA-ILD is prevalent in anywhere from 10–30% of patients with RA and can show radiographic progression in 60% of patients over an 18-month period. It can shorten life spans compared with RA patients without ILD, and has a significant impact on quality of life, with RA-ILD patients scoring the same or worse on quality-of-life measures as those with idiopathic pulmonary fibrosis (IPF), a progressive fatal fibrosing interstitial pneumonia.^2-7

In addition to its impact on mortality and quality of life, the presence of ILD in RA further increases the burden on the healthcare system, with a mean total five-year healthcare cost for RA-ILD subjects in the U.S. of $173,405 per patient over five years. In the U.S. alone that leads to an annual excess healthcare cost of $19.3 billion.⁸

Paul: Wow, I think what really gets the attention of the rheumatologist is that the type of lung disease that RA patients are prone to can be as bad as the dreaded IPF diagnosis, which for years had no treatment until the recent approval of two antifibrotics. That said, even with these new agents, they are not a cure and only slow disease progression—although it is a start.

Josh: Right, Paul, it is a start, and the former nihilism with fibrotic lung disease has really gone 180º, given that there are treatment options and multiple clinical trials available for patients. That brings us to how we as clinicians approach RA patients in the year 2021 and assess their risk for ILD, which will help us decide how to screen for ILD. To be honest, Paul, I think responsibility for this falls predominately on the shoulders of your tribe, the rheumatologists.

Paul: It always comes down to tribe doesn’t it; so RA-ILD is the rheumatologist’s fault?

Josh: No, what I mean is that the vast majority of patients with RA-ILD present to a rheumatologist first and get the bulk of their care from rheumatologist, so assessment for risk for ILD starts with them. It’s only later that pulmonologists like me get involved, and frankly it can be late in the game, at which point lung transplant may be the only viable option.

Paul: I hear you. So really what is important as a starting point is to get a better handle on what rheumatologists understand right now about RA-ILD, known risk factors and their attitudes toward evaluation and therapies. It just so happens that this was the major question on our minds when we conducted our international survey looking at the attitudes and practices of rheumatologists and pulmonologists regarding RA-ILD.¹ Can you summarize some of the major findings of our survey?

Josh: Happy to, Paul. First we found that up to 25% of rheumatologists underestimate the prevalence of ILD in RA, but that their overall understanding of known risks factors for RA-ILD (e.g., smoking, seropositivity, older than 55, male) was very high.

Regarding screening strategies in RA-ILD, a significant number of rheumatologists still consider chest X-ray as a screening tool, which is clearly not adequate for the detection of ILD, especially early ILD.

Also, when we presented respondents with a variety of clinical scenarios of RA patients at risk for, or likely to have, ILD, the majority of rheumatologists initiated a pulmonary evaluation when the scenario patient had clinical symptoms or physical signs, but nearly half of the rheumatologists declined to initiate a screening pulmonary evaluation of any sort in an asymptomatic patient with multiple identifiable risk factors for ILD. Quite concerning was that in those scenarios in which ILD was likely or evident, only a third of rheumatologists considered a pulmonary referral as part of the patient’s clinical care.

Paul: So rheumatologists understand what constitutes risk but the threshold to look for ILD seems pretty high—either the patient is coughing or short of breath or they have crackles on lung exam—and that is most definitely not what we call screening. So we really need better education, information and guidance for our rheumatology colleagues on who and how to consider screening, which has not been established by any of the professional societies to this point.

Josh: We sure do, and I think that what we need to offer is clearer guidance going forward with what we know, and at this point that will mean a consensus approach among experts in both rheumatology and pulmonary medicine until better data are available.

Where do you think the field is going, Paul?

‘We really need better education, information & guidance for our rheumatology colleagues on who & how to consider screening [for ILD], which has not been established by any of the professional societies to this point.’ —Dr. Dellaripa

Paul: Josh, I think as we gain more insight into who is at risk via genetic data like MUC5B, proteomics and other biomarkers, such as certain isosforms of ACPA, that many of our colleagues (and you) are working on, we will be able to combine those with our available clinical risk factors to better assess risk probability and then offer more clear recommendations on who and when to screen.

It’s a real challenge. The natural history of RA-ILD, which is still incompletely understood, suggests that ILD in RA doesn’t start on day 1 of RA onset in most patients, but maybe several or many years later.

The idea of serial CT scanning in all patients is not practical—or advisable from a radiation exposure standpoint—and not at all economically feasible in most parts of the world where resources are limited. Serial pulmonary function tests (PFTs) is another approach, although not specific for ILD. Maybe lung ultrasound (US) can help us, given its emerging use in ILD and other lung disorders?

Josh: You rheumatologists have really embraced US haven’t you? But all kidding aside, if US is a tool that can identify early ILD and clinicians can be trained in it, that could be one approach to screening or perhaps a combination of tools like PFTs and emerging biomarkers and molecular tools that we don’t have just yet is another approach. In fact, there may be more than one way to screen based on resource and available expertise. But I think that part of our charge right now, based on our survey data, is that we still have a lot of important education to do, not just on the rheumatology end of things but also on the pulmonary side, I dare say.

Paul: More education, I agree, Josh, and most certainly better cooperation between rheumatology and pulmonary medicine, a lower threshold for referral embedded within a multidisciplinary approach to identify and care for these most challenging patients.

Josh: Amen to that, Paul. Sharing our thoughts today has lowered my angst on this important topic. We have to keep this going.

Paul: I feel more hopeful too. And yes, I am certain this will not be our last conversation on this topic.

Joshua J. Solomon, MD, is a pulmonologist in the Division of Pulmonary, Critical Care and Sleep Medicine, an associate professor of medicine and director of the Interstitial Lung Disease Program at National Jewish Health, Denver.

Paul F. Dellaripa, MD, is an associate professor, at Harvard Medical School, Boston, and a rheumatologist at the Brigham and Women’s Hospital, Boston.

Disclosures

Dr. Solomon has received research funding from BI, Pfizer and the National Institutes of Health.

Dr. Dellaripa has received funding from Up to Date and Genentech, and serves on an FDA Advisory Committee.

References

1. Solomon JJ, Swigris JJ, Kreuter M, et al. The attitudes and practices of physicians caring for patients with rheumatoid arthritis-interstitial lung disease: An international survey. Rheumatology (Oxford). 2021 Jul 14:keab552. doi: 10.1093/rheumatology/keab552. Epub ahead of print.
2. Olson AL, Swigris JJ, Sprunger DB, et al. Rheumatoid arthritis-interstitial lung disease-associated mortality. Am J Respir Crit Care Med. 2011 Feb 1;183(3):372–378.
3. Gochuico BR, Avila NA, Chow CK, et al. Progressive preclinical interstitial lung disease in rheumatoid arthritis. Arch Intern Med. 2008 Jan 28;168(2):159–166.
4. Bongartz T, Nannini C, Medina-Velasquez YF, et al. Incidence and mortality of interstitial lung disease in rheumatoid arthritis: A population-based study. Arthritis Rheum. 2010 Jun;62(6):1583–1591.
5. Natalini JG, Swigris JJ, Morisset J, et al. Understanding the determinants of health-related quality of life in rheumatoid arthritis-associated interstitial lung disease. Respir Med. 2017 Jun;127:1–6.
6. Birnbaum H, Pike C, Kaufman R, et al. Societal cost of rheumatoid arthritis patients in the US. Curr Med Res Opin. 2010 Jan;26(1):77–90.
7. Palomäki A, Palotie A, Koskela J, et al. Lifetime risk of rheumatoid arthritis-associated interstitial lung disease in MUC5B mutation carriers. Annals Rheum Dis. 2021 Aug 3; annrheumdis-2021-220698. doi: 10.1136/annrheumdis-2021-220698.
8. Raimundo K, Solomon JJ, Olson AL, et al. Rheumatoid arthritis–interstitial lung disease in the United States: Prevalence, incidence, and healthcare costs and mortality. J Rheumatol. 2019 Apr;46(4):360–369.