What you need to know about Scleroderma and Lung Disease - Dr. Selvan

Interstitial lung disease (ILD) is a common complication of scleroderma that leads to inflammation and scarring of the lungs. In this session, we will review the prevalence of scleroderma-associated ILD (SSc-ILD), classic symptoms, and the approach to evaluating patients with suspected disease. In addition, we will cover various treatments available for patients with SSc-ILD.

This talk was presented at the Scleroderma Patient Education Conference on May 4, 2024, hosted by the Scleroderma Foundation of Greater Chicago.

For more info about scleroderma and the foundation, head to www.stopscleroderma.org

1. Scleroderma and Interstitial Lung Disease May 4, 2024 Kavitha Selvan, MD Clinical Instructor of Medicine Section of Pulmonary and Critical Care Medicine University of Chicago

2. Disclosures I have no financial disclosures. 2

3. Outline What is interstitial lung disease (ILD)? Who is at risk for developing ILD? What are the signs and symptoms of ILD? What type of testing is required to diagnose and monitor ILD? How is scleroderma-associated ILD treated? 3

4. What is interstitial lung disease (ILD)? 4

5. Interstitial Lung Disease (ILD) Family of over 200 different diseases that lead to inflammation and/or scarring of the lungs Scarring referred to as “ pulmonary fibrosis ” Can affect the walls of the air sacs (alveoli), the tissue, and the space around the air sacs ( interstitium ) 5

6. Who is at risk for developing ILD? 6

7. Causes of ILD 7

8. Scleroderma and ILD ( SSc -ILD) Between 35-53% of patients with scleroderma develop ILD Lung = 2 nd most affected organ Risk factors for developing ILD: Male gender Older age at time of diagnosis African American race Diffuse cutaneous form of scleroderma (vs. limited) Positive anti-Scl-70 antibody Negative anti-centromere antibody Cottin V, et al. Respir Res 2019;20:13. Khanna D. et al. J Scleroderma Relat Disord 2022;7(3):168-78. 8

9. Scleroderma and ILD ( SSc -ILD) Disease course can be variable Stable disease over time (~1/3 patients) Disease progression, followed by stability Progressive disease Leading cause of morbidity in scleroderma Outcomes worse with fibrotic patterns Outcomes better than idiopathic pulmonary fibrosis (IPF) Hoffmann- Vold AM, et al. Arthritis Rheumatol  2018; 70: A799. Early diagnosis and prompt initiation of treatment is KEY! 9

10. Scleroderma and ILD ( SSc -ILD) Most likely to progress within the first 5 years following disease onset Risk factors for disease progression: Gastroesophageal reflux disease (GERD) Greater than 20% fibrosis on HRCT Decreased lung function at baseline Reduced SpO2 at baseline Positive anti-Scl-70 antibody Hoffmann- Vold AM, et al. Arthritis Rheumatol  2018; 70: A799. 10

11. What are the signs and symptoms of ILD? 11

12. Signs of ILD Low oxygen levels Digital clubbing Pulmonary crackles 12

13. Symptoms of ILD Most common = shortness of breath and dry cough May be mild or absent in early disease Often occurs with exertion Fatigue Weakness Chest discomfort Loss of appetite Weight loss Some patients are asymptomatic ! 13

14. DO NOT IGNORE YOUR SYMPTOMS!! Diagnosis is delayed by 1-2 years in over half of patients Delays caused by: Symptoms being minimized Misdiagnosis Lack of reporting of early imaging findings Delay in referral Rahman KKM, et al. Eur Respir J 2016;48:PA861. Pritchard D, et al. Respir Res 2019;20:253. 14

15. Time Lost is Lung Lost 15

16. What type of testing is required to diagnose and monitor ILD? 16

17. Diagnostic Testing for ILD Pulmonary function tests High-resolution CT (HRCT) chest +/- Bronchoscopy and/or tissue biopsy 17

18. Diagnostic Testing for ILD Pulmonary function tests High-resolution CT (HRCT) chest +/- Bronchoscopy and/or tissue biopsy 18

19. Pulmonary Function Tests 19

20. Diagnostic Testing for ILD Pulmonary function tests High-resolution CT (HRCT) chest +/- Bronchoscopy and/or tissue biopsy 20

21. High-resolution CT Chest (HRCT) Most sensitive, non-invasive test for diagnosing SSc -ILD Obtain prone (left), supine (right), and expiratory images Considerations: Radiation exposure (0.2-0.98 mSv) 21

22. High-resolution CT Chest (HRCT) NORMAL Airway Blood vessel Heart Front Back Right Left Spine 22

23. Scleroderma-ILD ( SSc -ILD) INFLAMMATION “Ground-glass opacities” or “GGOs” Image source: Chung JH, et al. J Vis Exp 2020. 23

24. Scleroderma-ILD ( SSc -ILD) FIBROSIS “Traction bronchiectasis” and “honeycombing” or “honeycomb cysts” Airway Blood vessel Image source: Chung JH, et al. J Vis Exp 2020. 24

25. Scleroderma-ILD ( SSc -ILD) INFLAMMATION & FIBROSIS “Reticulation” or “reticular opacities” Image source: Chung JH, et al. J Vis Exp 2020. 25

26. Diagnostic Testing for ILD Pulmonary function tests High-resolution CT (HRCT) chest +/- Bronchoscopy and/or tissue biopsy 26

27. Bronchoscopy +/- Tissue Biopsy Image source: drugs.com 27

28. How is scleroderma-associated ILD treated ? 28

29. Treatment Immunosuppression Anti-fibrotic medications Supplemental oxygen Pulmonary rehabilitation 29

30. Treatment Immunosuppression Anti-fibrotic medications Supplemental oxygen Pulmonary rehabilitation 30

31. Immuno-suppression Raghu G, et al. Am J Respir Crit Care Med 2024;209(2):137-152. When should treatment be initiated? 31

32. Mycophenolate Mofetil ( CellCept ) Dosing : 500mg twice daily, increase up to 1500mg twice daily Side effects : Diarrhea, infection, skin cancer Monitoring : Blood counts, liver function tests (every 3 months) Tashkin DP, et al. Lancet Respir Med 2016; 4:708-719. Improved lung function at 2-years Better tolerated and improved survival vs. cyclophosphamide (SLS-II, 2016) 32

33. Rituximab Meta-analysis of 3 available trials found: Reduced decline in FVC by 3.3% vs. placebo at 24-48 weeks No significant difference in survival Dosing : 1000 mg injections on days 1 and 15, every 6 months Side effects : Infection (reactivation of Hep B), infusion reaction, progressive multifocal encephalopathy (PML) Monitoring : Screen for Hep B, Blood counts prior to infusions and monthly Raghu G, et al. Am J Respir Crit Care Med 2024;209(2):137-152. 33

34. Tocilizumab Improved lung function at 2-years ( focuSSced Trial, 2020) Dosing : 162 mg injection weekly Side effects : Diverticulitis/GI perforation, infection, hepatitis, anaphylaxis Monitoring : Screen for TB, Blood counts and liver function tests every 1-2 months x6 months, followed by every 3 months Khanna D, et al. Lancet Respir Med 2020;8:963-74 34

35. Treatment Immunosuppression Anti-fibrotic medications Supplemental oxygen Pulmonary rehabilitation 35

36. Anti-fibrotic Medications Nintedanib – SENSCIS Trial (2019) Reduced annual rate of FVC decline vs. placebo Pirfenidone – currently not approved, requires further investigation Distler O, et al. NEJM 2019;380(6):2518-2528. Raghu G, et al. Am J Respir Crit Care Med 2024;209(2):137-152. 36

37. Treatment Immunosuppression Anti-fibrotic medications Supplemental oxygen Pulmonary rehabilitation 37

38. Supplemental Oxygen Monitor resting and exertional oxygen levels with 6-minute walk test (6MWT) Initiate supplemental oxygen when resting SpO2 < 90% - may improve survival! Consider if ambulatory SpO2 < 88% Improves quality of life and breathlessness ( AmbOx Trial, 2018) Visca D, et al. Lancet Respir Med  2018; 6: 759–770. Jacobs SS, et al. Am J Respir Crit Care Med  2020; 202: e121–e141. 38

39. Treatment Immunosuppression Anti-fibrotic medications Supplemental oxygen Pulmonary rehabilitation 39

40. Pulmonary Rehabilitation Supervised program that includes: Breathing techniques Exercise training: High intensity exercises >> low intensity Health education Psychological counseling Nutritional counseling 2-3 sessions per week for 1-3 months https:// www.nhlbi.nih.gov /health-topics/pulmonary-rehabilitation 40

41. Benefits of Pulmonary Rehabilitation Increased walk distance (40 meters in 6 minutes) Decreased shortness of breath Improved quality of life Benefits often persist 6-12 months after completion of rehab! Dowman L et al. Cochrane Database of Systematic Reviews 2021, Issue 2. Art. No.: CD006322. 41

42. Additional Therapies Management of co-existing medical conditions Tobacco use disorder Obesity Congestive heart failure Immunizations Pneumococcal vaccine Seasonal influenza COVID-19 42

43. Questions? Thank you to the Scleroderma Foundation of Greater Chicago ! Patient resources : Pulmonary Fibrosis Foundation (PFF): pulmonaryfibrosis.org Contact information: Kavitha Selvan, MD Clinical Instructor of Medicine Section of Pulmonary and Critical Care Medicine University of Chicago Email: [email protected] 43