For patients living with pulmonary fibrosis, treatment options are limited to antifibrotic therapies. While the medications work to help slow the progression of the disease, they do little to meaningfully impact quality of life.
Kerri Aronson, MD, MS, a pulmonologist at NewYork-Presbyterian and Weill Cornell Medicine, is dedicated to the care of patients with interstitial lung disease (ILD) and pulmonary fibrosis. While she is optimistic about treatment options on the horizon, there is one aspect of research where additional strides need to be made: incorporating and addressing patient-reported outcomes (PROs). Below, Dr. Aronson discusses why PROs are essential and how they can and should be incorporated into clinical trials.
The Importance of the Patient Experience
Along with developing pulmonary fibrosis and scarring, patients with interstitial lung disease often suffer many negative symptoms that can impact their quality of life — and unfortunately, the treatment options we have available, nintedanib and pirfenidone, don’t really address them. We need to better identify therapies that not only address disease progression, but that also improve some of these symptoms. That’s where patient-reported outcomes come in.
For the majority of current clinical trials for ILD and pulmonary fibrosis, the primary endpoint is forced vital capacity (FVC). We know that FVC correlates well with survival; if somebody has a decline in their FVC, they have an increased risk of mortality. However, what’s less clear is how well FVC correlates with how people feel and function — in fact, there’s a lot of data that shows the two don’t correlate well.
While we can tell patients we have treatments for their disease, we can’t necessarily tell them that they are going to feel better because of the gap in research that actually looks at a patient’s lived experience.
— Dr. Kerri Aronson
There are a lot of unsavory side effects that accompany antifibrotic therapies. For nintedanib, about 60% of patients will have some level of diarrhea, sometimes severe. It can also cause inflammation in the liver, which requires frequent blood draws to monitor liver function. The other antifibrotic therapy, pirfenidone, causes a lot of gastrointestinal side effects as well as fatigue. This means that while we can tell patients we have treatments for their disease, we can’t necessarily tell them that they are going to feel better because of the gap in research that actually looks at a patient’s lived experience.
This is an important study as it shares evidence of how this antifibrotic therapy impacts patient’s quality of life beyond just disease progression.
— Dr. Kerri Aronson
There’s currently a big push to elevate PROs in studies to measure how treatments are working. I recently published an editorial in the European Respiratory Journal with my NewYork-Presbyterian and Weill Cornell Medicine colleague Anna Podolanczuk, MD, MS, in which we looked at a recent study examining the effect of nintedanib on the symptoms and impacts of pulmonary fibrosis, as measured by the Living with Pulmonary Fibrosis (L-PF) questionnaire in the INBUILD study. The L-PF questionnaire is composed of a symptoms module with three domains – cough, dyspnea, and fatigue – and a module on the impacts of pulmonary fibrosis, which were developed with the incorporation of patient input. The INBUILD study of nintedanib found that the medication decreases the rate of decline in lung function; however, there was no meaningful impact on quality-of-life measures. When investigators examined results using the L-PF there was evidence that, along with slowing lung function decline, nintedanib may slow the worsening of dyspnea and fatigue; stabilizes the degree of impact of pulmonary fibrosis; and may improve cough.
This is an important study as it shares evidence of how this antifibrotic therapy impacts patient’s quality of life beyond just disease progression. The L-PF is an example a PRO that has been developed and rigorously testing in the patient population of interest (in this case patients with pulmonary fibrosis) and its potential for incorporation into future clinical trials. The questionnaire was developed through interviewing patients with lived experience with pulmonary fibrosis in order to ensure that it really represented what matters to them.
There’s a whole science around what to include in PROs and how to develop them. This needs to be done rigorously to really understand how well a treatment is working — or not working — to help with symptoms, side effects, or quality of life.
— Dr. Kerri Aronson
But we still have a long way to go in our field when it comes to incorporating PROs in research. To that end, I and my colleagues have developed questionnaires from scratch as well as evaluated how well existing questionnaires measure symptoms and are representative of the experiences of people with ILD and pulmonary fibrosis. I recently looked at the University of California, Davis Shortness of Breath Questionnaire to evaluate what is the minimally clinically important difference for different types of pulmonary fibrosis. I’m also working on development of a PRO that measures quality of life in patients with hypersensitivity pneumonitis to better define, understand, and address the psychosocial challenges of living with the disease, for example, those associated with antigen identification and avoidance.
There’s a whole science around what to include in PROs and how to develop them. This needs to be done rigorously to really understand how well a treatment is working — or not working — to help with symptoms, side effects, or quality of life. In the PF field, we need to acknowledge that our patients live with an often progressive illness and right now, we don’t have a treatment that stops it. So, while we’re slowing down the progression of the disease, we also need to make it a priority to figure out how we can help our patients feel the best they can and maximize quality of life while they are living with the disease.
