Emerging Therapies for Lung Fibrosis Helen Garthwaite Respiratory - - PowerPoint PPT Presentation
Emerging Therapies for Lung Fibrosis Helen Garthwaite Respiratory Registrar/ Clinical Research Fellow Lung Fibrosis/Interstitial Lung Disease Disease that affects the IMPORTANT tissue that supports the lungs alveoli Inflammation and/or
Helen Garthwaite Respiratory Registrar/ Clinical Research Fellow
Disease that affects the tissue that supports the lungs alveoli Inflammation and/or scarring which interferes with breathing at the level
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broad spectrum of disease
Difficult to diagnose Lungs have huge reserve Skin and joint symptoms may prevent early detection Multiple causes of breathlessness Difficult to treat Fibrosis once established largely irreversible Primary aim of treatment is to prevent progression and induce stability
Induction therapy Maintenance therapy Cyclophosphamide Mycophenolate mofetil Azathioprine
Induction therapy Maintenance therapy Cyclophosphamide Mycophenolate mofetil Azathioprine Mycophenolate (SLS II) Rituximab T
Anti-fibrotic drugs; Pirfenidone Nintedanib
Chimeric monoclonal antibody against CD20 expressed on B cells Increased B cells in lungs
Intravenous therapy – two doses two weeks apart
Retrospective review of 50 patients who received Rituximab 33 with connective tissue disease – 8 scleroderma FVC pre treatment demonstrated a median decline of -13.3% FVC post treatment demonstrated a median improvement of +8.9% Click to edit Master text styles
Second level
Respirology April 2014. 19 (3) p353-359. Keir GJ et al
Not everyone responded – 5 of the connective tissue disease patients progressed in spite of rituximab In those that did respond; FVC decline was less pronounced pre rituximab FVC was higher pre treatment
14 patients in total 8 patients received 2 cycles of Rituximab 6 months apart Importantly no deterioration in the Rituximab group versus 5
Improvement in lung function tests; median improvement in FVC predicted 10%
Experience with rituximab in scleroderma: results from a 1 year, proof of principle study. Rheumatology 2010; 49: 271-280. Daoussis et al.
Experience with rituximab in scleroderma: results from a 1 year, proof of principle study. Rheumatology 2010; 49: 271-280. Daoussis D et al
Induction therapy Maintenance therapy Mycophenolate (SLS II) Rituximab Tocilizumab Anti-fibrotic drugs; Pirfenidone Nintedanib
Treatments developed for idiopathic pulmonary fibrosis Progressive fibrotic disease No effective treatment until recently Pirfenidone licensed for treatment of IPF in UK Nintedanib awaiting appraisal Slow rate of decline/progression
Oral medication Three randomised controlled trials showed benefit in IPF Reduction in decline of FVC from -11% (placebo) to -8.5% with treatment Number of people with a significant decline in lung function was halved over a year of follow up
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Oral medication Annual rate of FVC decline was 50% less in those taking the treatment
nd Change from Baseline over Time in Forced Vital Capacity (FVC) in INPULSIS-1 and INPULSIS-2, Accord
Richeldi L et al. N Engl J Med 2014;370:2071-2082.
Definitely important Despite challenges current treatment can potentially achieve stability Future treatments may be better tolerated and more efficacous Research activity
Inflammation Immune dyregulation Scar tissue formation - fibrosis Vasculopathy Aberrant tissue repair Amplifies autoimmunity Activation of immune pathways CY LC O MMF Rituximab T
Pirfenidone Nintedanib Vascular protective drugs