Progressive Pulmonary Fibrosis: Treatment and Support

MILAN ― Numerous unresolved questions surround progressive pulmonary fibrosis (PPF) treatment, according to Elisabeth Bendstrup, MD, PhD, a researcher and clinical professor in the Department of Clinical Medicine ― Department of Respiratory Diseases and Allergy, Aarhus University, Denmark. These questions regard the optimal timing for treatment initiation, the role of available medications, either as monotherapy or in combination, and nonpharmacologic support options.

What’s in the Toolbox?

Pulmonologists who manage PPF have a range of treatment options at their disposal. This includes careful patient observation, with treatment initiation based on clinical necessity. The therapeutic arsenal comprises immunomodulatory treatments, antifibrotic agents, palliative and supportive care, and, for a minority of patients, lung transplantation.

“Once a patient is diagnosed with PPF, it is important to remember that the diagnostic criteria from the guidelines are not exactly the same of those accepted for the reimbursement of antifibrotic treatments in different countries,” Bendstrup said, suggesting that nonclinical considerations could also potentially influence the treatment choice. She spoke at the European Respiratory Society (ERS) 2023 International Congress, in Milan, Italy.

Talking to Medscape, Michael Kreuter, MD, director of the Lung Center at the University Hospital in Mainz, Germany, provided insight into the introduction of antifibrotic drugs for the treatment of PPF. Drawing from nearly a decade ago when the first antifibrotic medication was approved for idiopathic pulmonary fibrosis (IPF), Kreuter noted its effectiveness in slowing disease progression, although it does not reverse it. Subsequently, the discovery that non-IPF diseases, such as rheumatoid arthritis (RA), exhibited IPF-like behavior led to the exploration of the use of the same drugs for similar conditions, even if not IPF.

“That’s how antifibrotic treatments came into place. Now we have more trials and data to be discussed in the future,” Kreuter added. He highlighted that antifibrotic drugs are effective for several diseases. Most of those diseases are treated with different anti-inflammatory drugs, which makes it difficult to decide when to start antifibrotic therapy and how to eventually combine it with different pharmacologic approaches.

A Pivotal Starting Point

One of the primary challenges faced by pulmonologists in the management of PPF is determining the appropriate timing for initiating treatment, a question only partially addressed by existing guidelines. Bendstrup advocated for a comprehensive baseline evaluation. Factors to be considered include symptom burden, the severity of lung decline, radiologic characteristics, signs of alveolar inflammation, progression risk factors, quality of life, patient preferences, and medical history. “All these should be best discussed in a multidisciplinary team, including pulmonologists, nurses, experts in palliative care, occupational physicians, and more,” she said.

Current guidelines recommend nintedanib for PPF treatment for patients who have failed standard management for fibrotic interstitial lung disease (ILD) other than IPF. However, the definition of “standard management” remains a topic of debate, and it is acknowledged that evidence-based guidance for a standard of care varies among patients. Bendstrup pointed out the limited guidance clinicians receive from these guidelines. “As clinicians, we are not left with very much help from here,” she commented.

Choosing the Right Approach

Bendstrup delved into the factors influencing the choice between antifibrotic and anti-inflammatory therapies. This decision hinges on whether the patient presents with a predominantly inflammatory or a fibrotic progressive phenotype. Certain clinical characteristics contribute to the decision. Factors such as younger age, female gender, and the presence of connective tissue disease lean toward an inflammatory phenotype. Radiologic patterns, such as organized pneumonia, hypersensitivity pneumonia, or UIP-like patterns also provide valuable clues. Additionally, genetics plays a role, with shorter telomeres indicating a more fibrotic phenotype and an increased risk of immunomodulatory treatment side effects in non-IPF ILDs.

Bendstrup referrerd to a recent position paper on treatment recommendations and many other studies that support the use of different treatments for patients with PPF. The authors highlighted limited evidence for immunomodulation in fibrotic ILD, though such treatment is generally used except for ILD associated with systemic sclerosis. Moreover, the guidelines conditionally recommend nintedanib and call for further research on pirfenidone in PPF.

“We need intelligent, well-designed trials looking at subgroups of patients at higher risk, maybe based on molecular identification. We also need to have good biomarkers to better classify our patients based on disease behavior and treatment response. There’s a lot of discussion of biomarkers for progression, much less ― if any ― on biomarkers for the response to treatment. And we need them as well,” Bendstrup told Medscape.

The Role of Supportive Care

Effective PPF treatment extends beyond pharmacologic interventions. It encompasses symptom management, patient education on vaccination and smoking cessation, and fostering social support networks. Psychological support, supplemental oxygen therapy, and pulmonary rehabilitation are integral components of care.

Elisabeth Robertson, a PPF patient representative from the UK, emphasized the importance of palliative care, not just in end-of-life scenarios but throughout the patient’s journey. Palliative care encompasses symptom alleviation, enabling patients to stay at home when possible, addressing mental health, and preparing for the end of life. Such holistic care can significantly enhance the patient’s quality of life.

The co-chair of the session, Marlies S. Wijsenbeek, MD, PhD, pulmonary physician and head of the ILD Centre at the Erasmus University Medical Centre in Rotterdam, the Netherlands, underscored that palliative care begins at diagnosis and involves managing symptom burdens. “Supportive care also includes nurses, as they are precious for the patients while answering their questions and can help save time for the doctors,” she commented to Medscape.

In the discussion on treatment decisions, experts agreed on the pivotal role of patients in decision-making. However, Kreuter highlighted two critical factors that influence successful patient-doctor interactions: the cultural backgrounds of patients and their relatives, and the attitudes of healthcare providers.

Bendstrup has received honoraria or consultation fees from Boehringer Ingelheim, Roche, Astra Zeneca, Chiesi, and Daiichi Sankyo. Robertson has disclosed no relevant financial relationships.

European Respiratory Society (ERS) 2023 International Congress.

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