New research is providing clinicians with an overview of the role of immunosuppression therapy in non-idiopathic pulmonary fibrosis (IPF) interstitial lung disease (ILD).1
The data were presented at the American Thoracic Society (ATS) International Conference 2025 by Aman Pande, MD, MS, a pulmonary critical care physician at Cleveland Clinic, and suggest use of immunosuppressive treatment in this patient population may not meaningfully affect fibrosis progression.1
“It gets really tricky when you’ve got 200 different varieties of rare conditions,” Pande explained to HCPLive, citing the heterogeneity of ILD as a key barrier to effectively understanding and managing it.
IPF, which is considered to be a purely fibrotic disease and comprises a large majority of ILDs, was previously treated with immunosuppression, until the 2012 PANTHER trial revealed this approach is both ineffective and dangerous in this particular patient population.2 However, for patients with non-IPFs who have more underlying inflammatory components, the potential role of immunosuppression is not well understood.1
“If you set IPF aside and you look at all these other diseases where there is a component of underlying inflammation, we try to treat these with various immunosuppressants, and we think for individual patients that we are helping them,” Pande explained. “But as we know, this needs to be scientifically evaluated so that we can make sure that we’re doing the right thing.”
To address this gap in research, he and colleagues examined data from Cleveland Clinic’s registry of patients seen in their ILD clinic. Patients were grouped based on whether they were prescribed steroids and/or other immunosuppressants at the first visit. Investigators used propensity scores (PS) for treatment to balance covariates prior to outcome analyses. Follow-up pulmonary function data was analyzed to see how many patients had a 10% relative decline in forced vital capacity (FVC) over a 24-month period.1
Among a cohort of 657 patients, 338 (51.4%) were prescribed immunosuppression. Investigators noted these patients were younger (median age 62.6 vs 67.7 years), but had a higher comorbidity index, more impaired pulmonary function (FVC 2.46L [1.84, 3.16] vs 2.63L [2.08, 3.30]) and were more often on supplemental oxygen (37.9% vs 20.4%). Investigators called attention to 231 patients with connective tissue disease (CTD) ILD in the cohort, most of whom (73.6%) received immunosuppression.1
A total of 196 (29.8%) patients in the undifferentiated cohort went on to develop progressive fibrosis over the next 2 years, and 305 (46.4%) upon further observation (median, 4.2 years). The unadjusted odds ratio (OR) for progressive fibrosis over the first 2 years was 1.07 (95% CI, 0.76-1.49) which did not change after direct adjustment for PS. Further 1:1 PS matching yielded an OR for progression of 1.01, ATT weighting an OR of 0.92, and a final double robust approach an OR of 0.91 (95% CI, 0.57-1.47).1
“What we found was, by all these other methods, as soon as you start adjusting for the fact that the groups are unbalanced, you find there is absolutely no progression of fibrosis,” Pande said. “We would have liked to show the opposite, that it actually is protective, but it didn’t play out. But at least we can say that we’re not harming our patients by doing these things. Hopefully, down the line, we’ll be able to tease out which groups benefit more than others.”
Editors’ note: Pande has relevant disclosures with Boehringer Ingelheim.
References
Table of Contents
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- References
- Pande A, Chen PH, McCully J, et al. Treatment of Interstitial Lung Diseases With Immunosuppressant Medications. Abstract presented at the American Thoracic Society (ATS) International Conference 2025 in San Francisco, CA, from May 18 – May 21, 2025.
- The Idiopathic Pulmonary Fibrosis Clinical Research Network. Prednisone, Azathioprine, and N-Acetylcysteine for Pulmonary Fibrosis. N Engl J Med. doi:10.1056/NEJMoa1113354
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- Exploring Immunosuppression’s Role in ILD Treatment: an interview wiht Aman Pande, MD, MS
- Understanding Interstitial Lung Disease (ILD)
- The Role of Immunosuppression in ILD Management: Dr.Pande’s Viewpoint
- Commonly Used Immunosuppressants in ILD
- Benefits of Immunosuppression in ILD
- Potential Risks and Side Effects
- Monitoring and Management
- The Future of Immunosuppression in ILD Treatment
- Advancements in Personalized Medicine for ILD
- Case Study: managing CTD-ILD with Immunosuppression
- First-Hand Experience: A Patient’s Journey with Immunosuppression
- Practical Tips for Patients on Immunosuppression
- Current Research and Clinical Trials
- Immunosuppressant Medication Comparison
- Key Takeaways
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Pande A, Chen PH, McCully J, et al. Treatment of Interstitial Lung Diseases With Immunosuppressant Medications. Abstract presented at the American Thoracic Society (ATS) International Conference 2025 in San Francisco, CA, from May 18 – May 21, 2025.
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The Idiopathic Pulmonary Fibrosis Clinical Research Network. Prednisone, Azathioprine, and N-Acetylcysteine for Pulmonary Fibrosis. N Engl J Med. doi:10.1056/NEJMoa1113354
date: 2025-05-18 21:35:00
Exploring Immunosuppression’s Role in ILD Treatment: an interview wiht Aman Pande, MD, MS
Interstitial Lung Disease (ILD) encompasses a group of disorders characterized by inflammation and scarring (fibrosis) of the lung tissue. Managing ILD effectively often requires a multifaceted approach, with immunosuppression playing a significant role. We delve into the intricacies of immunosuppression in ILD treatment, drawing upon the expert insights of Dr. Aman Pande, MD, MS, a leading pulmonologist with extensive experience in treating complex respiratory conditions.
Understanding Interstitial Lung Disease (ILD)
ILD isn’t just one disease; it’s an umbrella term for over 200 different lung conditions. These diseases cause progressive scarring of the lung tissue, making it difficult to breathe and causing shortness of breath, a persistent dry cough, fatigue, and eventually, decreased lung function. Some common types of ILD include:
- Idiopathic Pulmonary Fibrosis (IPF)
- Hypersensitivity Pneumonitis
- Connective Tissue Disease-Associated ILD (CTD-ILD), such as rheumatoid arthritis-ILD or scleroderma-ILD.
- Sarcoidosis
The underlying causes of ILD are diverse and sometimes unknown. while some cases are linked to environmental factors, occupational exposures, or certain medications, others are associated with autoimmune diseases.Accurate diagnosis, often involving high-resolution CT scans and sometimes lung biopsies, is crucial to guide treatment decisions.
The Role of Immunosuppression in ILD Management: Dr.Pande’s Viewpoint
Immunosuppressants are medications designed to suppress or weaken the body’s immune system. In ILD,particularly in cases driven by inflammatory or autoimmune processes,the immune system can mistakenly attack the lung tissue,contributing to inflammation and fibrosis. Dr. pande emphasizes that appropriate use of immunosuppressants can definitely help control inflammation, slow disease progression, and improve patients’ quality of life.
“The decision to use immunosuppressants in ILD treatment is a complex one,” Dr. Pande explains. “We carefully consider the specific type of ILD, the severity of the disease, the patient’s overall health, and potential risks and benefits of the medications. It’s a personalized approach, where we tailor the treatment plan to each individual’s needs.”
Commonly Used Immunosuppressants in ILD
Several immunosuppressant medications are commonly employed in ILD treatment. These include:
- Corticosteroids (e.g., Prednisone): These are often used as first-line agents to reduce inflammation. However, long-term use can have significant side effects, so they are typically used in combination with other immunosuppressants.
- Mycophenolate Mofetil (CellCept): This medication inhibits the proliferation of immune cells, helping to reduce inflammation and slow disease progression.
- Azathioprine (Imuran): Similar to mycophenolate, azathioprine suppresses immune cell activity. It’s frequently enough used as a steroid-sparing agent.
- Cyclophosphamide (cytoxan): This is a more potent immunosuppressant, usually reserved for severe cases of ILD or when other treatments have failed. It carries a higher risk of side effects.
- Rituximab (Rituxan): A biologic agent that targets B cells, a type of immune cell involved in inflammation. It’s often used in CTD-ILD.
Dr. Pande highlights that the choice of immunosuppressant depends on the underlying cause of the ILD and the individual patient’s clinical profile. He adds that the medications often work synergistically, so combinations of immunosuppressants may be used to achieve better disease control.
Benefits of Immunosuppression in ILD
When used appropriately, immunosuppression can offer significant benefits for individuals with ILD. These benefits might include:
- Reduced Inflammation: Suppressing the immune system calms inflammation in the lungs,leading to symptom relief.
- Slower Disease Progression: By controlling inflammation,immunosuppressants can slow down the progression of fibrosis,preserving lung function.
- improved Quality of Life: Reduced symptoms and improved lung function can lead to a better quality of life for patients with ILD.
- Potential for Lung Transplant: In certain specific cases where immunosuppression helps manage the ILD, it can keep patients healthier and in a better state of condition should they be considered a candidate for lung transplant.
Potential Risks and Side Effects
While immunosuppressants can be beneficial, they also carry potential risks and side effects. Dr. Pande emphasizes the importance of carefully monitoring patients for these side effects and taking steps to minimize them.Common side effects of immunosuppressants include:
- Increased Risk of Infections: Suppressing the immune system makes individuals more susceptible to infections.
- Gastrointestinal Issues: Nausea, vomiting, and diarrhea are common side effects of some immunosuppressants.
- Bone Marrow Suppression: Some immunosuppressants can decrease the production of blood cells, leading to anemia or increased risk of bleeding.
- Liver and Kidney Problems: Regular monitoring of liver and kidney function is essential.
- Increased Risk of Certain cancers: Long-term use of some immunosuppressants can increase the risk of certain cancers.
Dr. Pande stresses that the benefits of immunosuppression must always be weighed against the potential risks. He encourages patients to openly communicate with their healthcare providers about any concerns or side effects they may experience.
Monitoring and Management
Careful monitoring is crucial when using immunosuppressants, says Dr. Pande. This includes:
- Regular Blood Tests: To monitor blood cell counts, liver and kidney function, and drug levels.
- pulmonary Function Tests (PFTs): To assess lung function and track disease progression.
- Imaging Studies (e.g., CT Scans): To monitor changes in lung inflammation and fibrosis.
- Close Dialog with Healthcare Providers: Patients should promptly report any new symptoms or side effects.
Dr. Pande frequently enough tells his patients that immunosuppression therapy is a partnership, and they are a key part of their treatment strategy. This collaboration, along with active management of side effects, can make meaningful improvements in quality of life for those with ILD.
The Future of Immunosuppression in ILD Treatment
The field of ILD treatment is constantly evolving, with ongoing research exploring new and more targeted immunosuppressive therapies. Dr. Pande is optimistic about the future of ILD treatment, citing the potential of novel biologic agents and targeted therapies to provide more effective and safer treatment options.
“We’re seeing a shift towards more personalized medicine in ILD,” Dr. Pande notes. “As we gain a better understanding of the underlying mechanisms driving different types of ILD, we can develop treatments that are tailored to specific patient populations. This will lead to better outcomes and fewer side effects.”
Advancements in Personalized Medicine for ILD
Personalized medicine is revolutionizing ILD treatment by tailoring treatment approaches based on genetic profiles, biomarkers, and individual disease characteristics. This targeted approach aims to maximize efficacy while minimizing side effects. Here are some notable advancements:
- Genetic Testing: Identifying specific genetic mutations associated with ILD can help predict disease progression and guide treatment decisions.
- Biomarker Analysis: Measuring specific proteins or molecules in the blood or lung fluid can provide insights into disease activity and response to therapy.
- Multi-Omics Approaches: Combining genomics,proteomics,and metabolomics data to create a complete picture of the patient’s disease state.
Case Study: managing CTD-ILD with Immunosuppression
Mrs. L, a 62-year-old woman with rheumatoid arthritis, developed progressive shortness of breath and a dry cough. A high-resolution CT scan revealed findings consistent with CTD-ILD. After a thorough evaluation, Dr. Pande initiated treatment with mycophenolate mofetil and a low dose of prednisone. Over the next six months, Mrs. L experienced a significant improvement in her symptoms, and her pulmonary function tests stabilized. Regular monitoring helped to detect and manage any potential side effects of the medications. This case highlights the importance of early diagnosis and appropriate immunosuppression in managing CTD-ILD.
First-Hand Experience: A Patient’s Journey with Immunosuppression
John, a 55-year-old diagnosed with hypersensitivity pneumonitis due to mold exposure, shares his experience with immunosuppression:
“Being diagnosed with ILD was scary. Dr. Pande explained that my immune system was overreacting to the mold, causing inflammation in my lungs. He started me on prednisone to calm things down, then added azathioprine to help me get off the steroids.The first few weeks were tough with the side effects – nausea and fatigue – but Dr. Pande and his team were incredibly supportive. They adjusted my medications,gave me tips to manage the side effects,and kept a close eye on my progress. Six months in, I felt much better.My breathing was easier,and I had more energy. It’s not a cure, but it’s helped me live a more normal life.It’s crucial to trust your doctor and be open about any concerns.”
Practical Tips for Patients on Immunosuppression
Here are some practical tips for patients undergoing immunosuppressive therapy for ILD, inspired by Dr. Pande’s recommendations:
- minimize Infection Risk: practice good hygiene, wash hands frequently, avoid crowds during flu season, and get vaccinated against influenza and pneumonia.
- Maintain a Healthy Lifestyle: Eat a balanced diet, get regular exercise (as tolerated), and avoid smoking.
- Stay Hydrated: Drink plenty of fluids to help flush out medications and prevent dehydration.
- Manage Side Effects: Work closely with your healthcare team to manage any side effects of the medications. Don’t hesitate to report any new symptoms or concerns.
- Attend All Appointments: Regular check-ups and monitoring are crucial to ensure the safety and efficacy of the treatment.
- Build a Support System: connect with other ILD patients and support groups to share experiences and receive emotional support.
Current Research and Clinical Trials
Active participation in clinical trials can significantly impact the future of ILD treatments. Here are some key areas of ongoing research:
- New Immunosuppressive Agents: Development of more targeted and less toxic immunosuppressant medications.
- Fibrosis-Targeted Therapies: Identification of drugs that can directly inhibit the fibrotic process in the lungs.
- Early Detection Strategies: Development of biomarkers and imaging techniques for early detection of ILD.
- Lung Regeneration Therapies: Research into methods to repair or regenerate damaged lung tissue.
Patients can explore clinical trial opportunities thru their physicians and online resources like ClinicalTrials.gov.
Immunosuppressant Medication Comparison
| Medication | Common Use in ILD | Primary Side Effects | Monitoring |
|---|---|---|---|
| Prednisone | Initial inflammation control | weight gain, mood changes, increased infection risk | Blood glucose, bone density |
| Mycophenolate | Long-term inflammation suppression | GI upset, increased infection risk | CBC, liver & kidney function |
| azathioprine | Steroid-sparing agent | Bone marrow suppression, liver dysfunction | CBC, liver function |
| Rituximab | CTD-ILD targeting B-cells | Infusion reactions, increased infection risk | CBC, viral screenings |
Key Takeaways
Immunosuppression plays a vital role in managing ILD, particularly in cases involving inflammatory or autoimmune processes. Dr. Aman Pande’s insights highlight the complexities and nuances of this treatment approach. By carefully weighing the benefits and risks, and closely monitoring patients, healthcare providers can definitely help individuals with ILD achieve better outcomes and improved quality of life. Ongoing research and advancements in personalized medicine offer hope for even more effective and safer treatments in the future. Proactive communication between patients and their healthcare team is paramount for optimal outcomes.