Safety and efficacy of pirfenidone in patients with lung fibrosis and TERT mutation

Background Mutations within TERT and TERC are found in 15% of familial pulmonary fibrosis and are associated with hematologic, liver and dermatological disorders. Pirfenidone has been shown to limit FVC decline and to decrease 12 months mortality rate in idiopathic pulmonary fibrosis (IPF). To our knowledge, pirfenidone has not been specifically evaluated in carriers of TERT / TERC mutations. Objectives The aim of this multicenter retrospective French study was to evaluate the safety and efficacy of pirfenidone in carriers of TERT mutations. Results We identified 18 patients (11 men) with a TERT mutation who received pirfenidone: 16 IPF, 1 pneumoconiosis and 1 rheumatoid arthritis-associated ILD. At diagnosis, mean age was 59 ± 6 years, mean FVC was 78.0% ± 16.4 % and mean DLCO was 52.4± 10.2%. The median duration of treatment was 304 days [14 -791]. Gastro intestinal intolerance was observed in 6 patients (33%). One patient showed a transient thrombocytopenia. Pirfenidone was discontinued in 10 patients (55%) due to disease progression (n=5, 28%), exacerbation (n=2, 11%), increased liver enzymes (n=2, 11%) or gastro intestinal intolerance (n=1, 5%). The median FVC decline was 32.6 mL [0-165] per month before pirfenidone initiation versus 35.7 mL [5-166] per month after treatment initiation; 7 patients showed an FVC decline >10% during treatment. Conclusion These preliminary data suggest that pirfenidone is safe in patients with TERT mutation. Disease progression is frequent in this population and does not seem to be influenced by pirfenidone.