PPF and Role of Pirfenidone May 2023 (1).pptx

Role of perfenidone in progressive pulmonary fibrosis

1. PPF and Role of Pirfenidone

2. ILDs IPF Non- IPF PPF Prevalence 30% Prevalence 70% 30% of Non-IPF ILDs progress to PPF

3. March 2023 T o provide expert guidance on diagnosis and treatment of PPF

4. A patient with non IPF ILDs (cHP, SSc-ILD, RA-ILD, uILD, Sarcoidosis) who progresses in their disease course despite standard management (steroids and/immunomodulators) Definition of progression Worsening of symptoms Absolute decline in FVC and DLco (10% or 5-10%) New signs of fibrosis – reticular abnormality, traction bronchiectasis, honeycombing Increased in extend of signs of fibrosis Increase in volume loss Progressive Pulmonary Fibrosis - Definition Raghu et al. Am J Respir Crit Care Med 2022; 205(9):e18-e47

5. Approximately 18% to 32% of non-IPF ILDs progress despite initial treatment within 61 to 80 months to develop PPF PPF

6. IPF Non IPF ILDs PPF Antifibrotic Immunosupprestants Immunosupprestants + Antifibrotic

7. Evidence with Pirfenidone in PPF TRAIL 1 study RELIEF study SLS III study Unclassifiable ILD

8. TRAIL 1 Study: To assess efficacy and safety in patients with RA-ILD and having PPF Randomised, double-blind, placebo-controlled, phase 2 trial N=123 patients Either received Pirfenidone (2403mg/d) or Placebo Duration 52 weeks P irfenidone slowed the rate of decline of FVC in patients with RA-ILD. Safety in patients with RA-ILD was similar to that seen in other pirfenidone trials. Lancet Respir Med 2022 September 5, 2022

9. Lancet Respir Med 2021; 9: 476–86 Multicenter , double-blind, randomised, placebo-controlled, parallel phase 2b trial Enrolled patients with progressive fibrotic ILD due to four diagnoses: collagen or vascular diseases (ie, connective tissue disease-associated ILDs), fibrotic non-specific interstitial pneumonia, chronic hypersensitivity pneumonitis, or asbestos-induced lung fibrosis RELIEF Study: To assess efficacy and safety in patients with PPF

10. 127 patients to treatment: 64 to pirfenidone, 63 to placebo. Max dose : 2403mg/d pirfenidone I n patients with fibrotic ILDs other than IPF who deteriorate despite conventional therapy, adding pirfenidone to existing treatment reduces disease progression as measured by decline in FVC Lancet Respir Med 2021; 9: 476–86

11. SLS 3 study: To assess efficacy and safety of Combination Therapy of Mycophenolate Mofetil and Pirfenidone vs. Mycophenolate Alone Investigator-initiated multi- center , double-blind, placebo (PLA)-controlled Phase II trial evaluated combination therapy (MMF+PFD vs MMF+PLA) in those with SSc-ILD. N= 51 participants  U pfront combination therapy (MMF+PFD) led to more rapid improvement in the FVC% (0-6 months) Changes in HRCT outcomes and patient-reported outcomes tended to favor MMF+PFD https://acrabstracts.org/abstract/combination-therapy-of-mycophenolate-mofetil-and-pirfenidone-vs-mycophenolate-alone-results-from-the-scleroderma-lung-study-iii/