Treating, Monitoring Patients With ILD Associated With Systemic Sclerosis

Interstitial lung disease (ILD) is a common, but serious complication of systemic sclerosis (SSc), a systemic autoimmune disease affecting multiple organ systems. But despite the known relationship between SSc-associated ILD (SSc-ILD) and its complications, there is still no consensus on screening for ILD, nor on monitoring for disease progression.  

In the absence of standardized monitoring methods, Elizabeth Volkmann, MD and her research team published a study with recommendations on how to combine both lung function tests and chest imaging to potentially identify those who are at-risk for disease progression. Dr. Volkmann is the director of the UCLA Scleroderma Program and the founder and codirector of the UCLA Connective Tissue Disease-Related Interstitial Lung Disease Program.

This Q&A was originally a podcast on the Rheumatology & Arthritis Learning Network and has been edited for length and clarity. To listen to the full-length podcast, please visit the Rheumatology & Arthritis Learning Network.

Rheumatology & Arthritis Learning Network: Can you explain why predicting the progression of interstitial lung disease is so important—and so difficult?

Elizabeth Volkmann, MD: That's an excellent question and important for the patients with systemic sclerosis. What we find is that some patients who have interstitial lung disease can have a very stable disease course. Even in the absence of therapy, their fibrosis in their lungs will not progress or get worse over time.

But then a subgroup of patients will have progressive disease, and sometimes this happens quite rapidly. Over the course of 1 to 2 years, patients can lose a significant amount of lung function, develop significant shortness of breath, even require supplemental oxygen, and sometimes, lung transplantation.

If we're able to predict which patients are going to be the more stable patients and which patients are going to be the more rapidly progressive patients, we can tailor the treatments for those patients to make sure that they're managed appropriately.

RALN: In your research article, you and your colleagues noted that there is no valid definition of disease progression at this point in interstitial lung disease. But you did suggest some criteria that may be useful to rheumatologists as they try to identify their patients who are at risk of progression or who are progressing. What can you tell us about what you proposed, and why?

Dr Volkmann: To measure progression of interstitial lung disease, whether it's due to scleroderma or any other disease associated with interstitial lung disease, I think it's most important to use a lot of different modalities.

Oftentimes, patients will undergo pulmonary function testing. These are breathing tests that they do. This can be very helpful, and if we see, for example, a decline in the forced vital capacity of more than 10%, this is a pretty good indicator that the patient has lost lung function and has had progression of their interstitial lung disease.

But sometimes, pulmonary function tests can be unreliable—if the patient maybe doesn't feel so well the day they do it, or if they have a different technician there. In that case, we can sometimes rely on other measurement tools, such as high-resolution chest computed tomography (CT). Looking at the radiographic images of the lungs can actually tell us how the fibrosis is progressing. We can see, is it getting worse in the lungs? Is there more ground glass, more reticulation? I use CT quite a lot in my practice to measure progression and also to try to understand how the disease is evolving.

In addition, one of the most important things is to ask patients about how they feel and their function, because this is probably more important to the patient than their numbers of forced vital capacity and their CT scores. I not only ask patients if they a feel shortness of breath or a cough, but I ask them a lot about their lifestyle.

Because very often, when patients develop this disease, they will modify their lifestyle to avoid feeling short of breath. They may say, "Oh, no, I don't feel short of breath," but then when you probe them further, they'll say, "Oh, but I never walk upstairs anymore. I always take the elevator," or, "I've stopped going for my evening walks with my partner." Asking about how a patient feels and function is also important.

RALN:  Your paper also mentioned that there's, again, no consensus on when to start or escalate treatment. Did you identify any criteria for when to begin treatment for interstitial lung disease and when or if to escalate or change therapy?

Dr Volkmann: As someone who treats a lot of these patients, I will tell you that early treatment makes a big difference in modifying their disease course.

If I identify interstitial lung disease in a patient with scleroderma and it's a relatively new diagnosis of scleroderma, I will often start therapy. Even in patients where there's a mild amount of interstitial lung disease, I will start therapy, because that's, to me, a sign that there's inflammation going on in the body.

If this disease progresses, it has a high risk of causing death. The interstitial lung disease is the leading cause of death in these patients. In very rare exceptions, I will not treat the interstitial lung disease, but I think most of the time, with a new diagnosis of interstitial lung disease, therapy is warranted, especially since we have a lot of treatment options now.

Then the second question about when to switch therapy is another important question, because there are patients that do very well with treatment such as mycophenolate, but then there are those that progress, despite treatment with mycophenolate and other therapies.

I typically wait about 6 months before I decide about switching therapies, because some of these medications can take a couple of months to titrate up to their most effective dose. You really want to give the medication a little bit of a try, but I don't think you want to wait too long. I wouldn't wait an entire year before making the treatment decision, because if the patient is progressing over the course of that year, it's going to be hard to reverse the damage that has been done.

RALN: What treatments are available, and what new treatments do you think are needed to have the biggest effect on patients with scleroderma and ILD?

Dr Volkmann: Right now, mycophenolate is still the first-line therapy that we use to treat interstitial lung disease and scleroderma. This comes from data from our Scleroderma Lung Study II, where mycophenolate was shown to be just as effective at treating the lung disease and also improving radiographic fibrosis and breathlessness as cyclophosphamide, but far safer than cyclophosphamide, and better tolerated. So we tend to use this as a first-line agent, but there are a number of other options now, too.

One is nintedanib, and this was FDA-approved in 2019 for the treatment of interstitial lung disease associated with systemic sclerosis. This is a medication that was shown to slow the decline of lung function in a very large population of patients with scleroderma-related interstitial lung throughout the world. In this study, about half of the patients were on background mycophenolate. Those patients who were on the background mycophenolate plus the nintedanib had the best course of disease over that study.

So I also sometimes add on nintedanib to mycophenolate, or if a patient is not responding to mycophenolate, I will then switch them to nintedanib.

RALN:  What advice would you give to rheumatologists who are caring for patients with systemic sclerosis—both those who've developed ILD and those without—in terms of signs to watch for, things to take into consideration as these patients progress and perhaps begin to show the signs of ILD?

Dr Volkmann: I think one of the most important things, and what we do well at UCLA, is providing multidisciplinary care.

Usually, these patients should not only be under the care of a rheumatologist, but they should be seeing a pulmonologist, too, a respiratory therapist, and working together as a team to make sure that the patient is being treated effectively and appropriately.

At our center, every patient that comes in is seen by a rheumatologist and pulmonologist, and then we make all of our diagnostic and treatment decisions together. There have been studies showing that this multidisciplinary approach to caring for patients with interstitial lung disease can lead to better patient satisfaction and also better accuracy in making these diagnoses. That's one of the most important things.

Another thing that's very important is close follow-up of these patients. These are not patients that you can say, "OK, come back in a year. Come back if you don't feel well." At a minimum, they should be seen every 3 months. At that visit, you should be assessing how they feel and function, what their pulmonary function test is, doing your physical exam, measuring their oxygen saturation. Again, you'd rather catch the signs of progression early on than wait a whole year.



  1. Distler O, Assassi S, Cottin V, et al. Predictors of progression in systemic sclerosis patients with interstitial lung disease. Eur Respir J. 2020;55:1902026. doi:10.1183/13993003.02026-2019
  2. Volkmann ER, Tashkin DP, LeClair H, et al. Treatmment with mycophenolate and cyclophosphamide leads to clinically meaningful improvements in patient-reported outcomes in scleroderma lung disease: results of scleroderma lung study II. ACR Open Rheumatol. 2020;2(6):362-370. doi:10.1002/acr2.11125