Elizabeth Volkmann, MD, on Treating and Monitoring Patients With SSc-ILD

In this podcast, Dr Volkmann discusses treatment and monitoring of patients with systemic sclerosis-related ILD.

Elizabeth Volkmann, MD, is director of the UCLA Scleroderma Program and the founder and codirector of the UCLA Connective Tissue Disease-Related Interstitial Lung Disease (CTD-ILD) Program.

TRANSCRIPT:

Rebecca Mashaw:  Welcome to another podcast from the Rheumatology and Arthritis Learning Network. I'm your moderator, Rebecca Mashaw.

I'm pleased to be joined today by Dr. Elizabeth Volkmann, director of the UCLA Scleroderma Program and codirector of the Connective Tissue Disease Interstitial Lung Disease Program. Thanks for joining us today, Dr. Volkmann.

Dr. Elizabeth Volkmann:  Hi, Rebecca. I'm delighted to be here today.

RALN:  To start us off, can you explain why predicting the progression of interstitial lung disease is so important—and so difficult?

Dr. Volkmann:  That's an excellent question and important for the patients who suffer from 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 ILD. 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 ILD, 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 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 how they feel and function, because this is probably more important to the patient than their numbers of FVC 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:  You further pointed out that there has been no consensus about the diagnostic tools that should be used in assessing progression—and you may have partially answered this in your previous answer about using CT. What have you learned in the course of your research about other diagnostic modalities that may be helpful, and what new modalities are needed or in development?

Dr. Volkmann:  Again, some of that was addressed, like you said, in the previous question. But in terms of the CT, what we do now is instead of just having a radiologist look at the CT and tell us it's getting worse or it's better at stable, we do something called quantitative image analysis. This is using a computer-based algorithm that objectively quantifies the extent of fibrosis in the lungs. In doing this, we're able to get an actual percentage and we can follow that percentage over time. It turns out that that's a much more sensitive way to look at progression than to just have a reader look at a CT scan, which can be subject to some bias.

We've also recently done some studies looking at data from 2 large clinical trials, the Scleroderma Lung Studies I and II. These were two large randomized controlled trials looking at treatments for scleroderma ILD. In these studies, we followed patients long-term to see how their health was many years after participating in these trials.

We found that in both of the studies, the changes in CT over the course of 1 to 2 years was highly predictive of their future survival. Those patients who had increased progression were more likely to experience mortality compared to those patients who did not.

Again, I think this is a really exciting measurement tool that's going to be used a lot more in the future, not just in our research studies, but also in clinical practice.

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 ILD and when or if to escalate or change therapy?

Dr. Volkmann:  In terms of those 2 questions, because they're very distinct issues—and again, there's no universal answer on this—but 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 ILD, 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 make a decision 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:  Again, you've partly answered my next question, which is what are the primary options for treatment available today, because you mentioned mycophenolate. 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 ILD 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 SSc-ILD. This is a medication that was shown to slow the decline of lung function in a very large population of patients with scleroderma-related ILD 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.

The most recently approved medication, though, is something called tocilizumab. This is a biologic medication that we've been using for years in diseases such as rheumatoid arthritis. It wasn't specifically a lung study, it was actually a study done to look at skin disease in patients with diffuse systemic sclerosis. In this study, it didn't meet its primary endpoint for improving skin disease compared with placebo, but they did find that those patients who got the tocilizumab did not have as much of a decline in their forced vital capacity compared to those patients who received placebo. This medication in the last year also received approval.

So this might be something to use in a patient who has early diffuse skin disease and also interstitial lung disease.

RALN:  What advice would you give to rheumatologists who are caring for patients with SSc— 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:  That's a wonderful question. 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.

We actually, 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.

RALN:  Do you have any last thoughts you'd like to share with your colleagues in rheumatology who may not be in an academic center, may not have easy access to that multidisciplinary team, about how they might go about bringing in people from other specialties to work with them?

Dr. Volkmann:  I think since the pandemic, we've improved our ability of connecting electronically. Now, we've all become experts in Zoom, and Microsoft Teams, and these different platforms. We actually transitioned our multidisciplinary group to Zoom, and this has allowed community pulmonologists and rheumatologists to also participate in our meeting.

I would encourage practitioners who do not work at academic centers to feel free to reach out to the nearest academic center. It could be even across the country, because there are ways to connect electronically.

We can even see these patients for virtual health visits so they don't have to fly to another state. We can connect with them virtually for a one-time consultation.

I think this is really the future of being able to provide the best care possible for these very complex patients.

RALN:  Thank you so much for your time today. This has been very interesting. We look forward to speaking with you again about new developments in the treatment of scleroderma and interstitial lung disease.

Dr. Volkmann:  Thank you so much. It was a pleasure. Take care.