AB0697 LOW DOSE CYCLOPHOSPHAMIDE AND PIRFENIDONE MIGHT WORK IN SYNERGY TO RELIEVE INTERSTITIAL LUNG DISEASE WITH CONNECTIVE TISSUE DISEASE: A PRELIMINARY OBSERVATIONAL STUDY

Background There are anti-inflammation and anti-fibrosis agents available for connective tissue disease associated interstitial lung disease (CTD-ILD). A clinical study has been initiated to assess the combination of the two (NCT03221257), but whether they can spare dose for each other is unknown. Objectives This preliminary study is aimed to observe outcomes of CTD-ILD patients receiving cyclophosphamide plus pirfenidone as a rescue therapy, with each agent at about one third of routine dosage. Methods We enrolled CTD-ILD patients who did not improve their symptoms (dyspnea or cough) after at least one-month steroids treatment (prednisone≥1mg/kg daily). Patients who had adjusted immunosuppressive agents other than steroids or had received anti-fibrotic medications within three months before enrollment were ruled out. We switched the treatment into pulse cyclophosphamide (0.4g/m2 monthly) combined with pirfenidone (300mg twice per day). Besides, we reduced the steroids to prednisone 0.5mg/kg daily and then tapered routinely. All the patients were followed up for 12 months. Results We enrolled seven patients, of whom two had anti-synthetase syndrome, two had Sjogren syndrome, two had scleroderma and one had mixed connective tissue disease. The media DLCO was 51% of prediction (range47.7% to 63%) and media FVC was 72.3% of prediction (range 39% to 81%). The media 6MWD was 275m (range202 to 324m). At the end of 12-month follow-up, all the patients regained functional independence with a media 52.7% increase of 6-minute walk distance (range34.4% - 86.3%). Pulmonary function tests showed improved forced vital capacity (median improvement 13.4%, range 0-35.9%) and DLCO (median improvement 6.3%, range 1.7%-16%). The HRCT score had a median decrease of 20.1% (range 11.7% to 29.6%). For quality of life assessment, the SGRQ total score had a median improvement of 53.3% (range 19.5% to 61.7%). Of note, no adverse events were observed during the 12-month follow-up. Conclusion Our Study provided preliminary but promising clinical evidence for a new strategy in treating CTD-ILD, that cyclophosphamide and pirfenidone might work in synergy and spare dose for each other. A well-designed controlled study is needed to further establish its safety and efficacy. References None. Disclosure of interests None declared