SAT0256 EFFICACY AND SAFETY OF ANTIFIBROTIC THERAPY IN DIFFUSE INTERSTITIAL PULMONARY DISEASE ASSOCIATED WITH SYSTEMIC AUTOIMMUNE DISEASES
Authors: Marta Aguilar-Zamora, J. Narváez, Juanjo J. Alegre-Sancho, Vanesa Vicens, Maria Molina, Joan Miquel Nolla
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Objectives:</h3> Assess the efficacy and safety of antifibrotic agents (pirfenidone and nintedanib) in refractory diffuse interstitial lung disease (DILD) associated with systemic autoimmune diseases (SAD). <h3>Methods:</h3> Open observational study in patients with active symptomatic DILD-SAD (evidence of clinical and functional impairment) despite treatment with glucocorticoids (GC) and immunosuppressant therapy. <h3>Results:</h3> We included 13 patients (8 women) with a mean age (± SD) of 55 ± 12 years (range, 27-71). The baseline SAD were: eighth systemic sclerosis, one rheumatoid arthritis, one ankylosing spondylitis, one microscopic polyangiitis with pulmonary fibrosis and one interstitial lung disease with autoimmune characteristics (IPAF). Mean time from diagnosis to initiation of antifibrotic therapy was 3 ± 8.2 years (IQR 25-75%: 1.6-9.5). The histopathological patterns found were: seven cases (54%) of usual interstitial pneumonia (UIP), three (23%) nonspecific interstitial pneumonia (NSIP), two cases (15%) combined pattern of pulmonary fibrosis plus emphysema (CPFE), and one (8%) non-classifiable pulmonary fibrosis (without histospecific radiological pattern). In addition to GC, the previous therapy tested for DIDL was mycophenolate mofetil (MMF) in 77% of the patients, cyclophosphamide (8 intravenous boluses) in 46%, and rituximab (RTX) in 54% (the number of RTX cycles administered were 4 ± 3.3; range, 1-9). Despite this, during the year prior to start the antifibrotic drugs, all patients presented a worsening in the values of % pFVC (-8.77%) and% pDLCO (-12.41%). Five (38%) patients received pirfenidone at doses of 3 tablets/8 hours (2403 mg/day) and eight (62%) nintedanib (5 at a dose of 150 mg/ 12 hours and 3 at a dose of 100 mg/ 12 hours). Antifibrotic therapy was administered in combination with MMF (1.5-2 g/day) in 10 patients (77%) and with rituximab in 3 (23%), in addition to GC at doses between 5 and 20 mg/ prednisone per day. The mean duration of follow-up was 15 months (range 3-59). At the end of the follow-up period, 10 of the 13 patients (77%) were still in treatment. In 2 patients (15%) the therapy failed, requiring lung transplantation in 1 case (after 7 months of therapy), while an autologous hematopoietic stem cell transplant was conducted in the other patient (after 13 months of antifibrotic). In one patient (8%) the treatment was discontinued due to adverse effects. When quantifying the degree of response in patients who continued treatment, only 9 of the 10 patients were included in the analysis, since 1 had only 3 months of therapy. In these 9 patients there was an improvement of% pFVC (mean: +5.13; SD: 8.38) and% pDLCO (+4.42; SD: 5.06). The evolution of the efficacy variables analyzed is shown in the table. The response in the Pulmonary function testing (PFT) in these 9 patients categorized according to the definitions of the American Thoracic Society was as follows: A)% pFVC: stabilization in 5 cases and improvement in 4; B)% pDLCO: stabilization in 7 cases and improvement in 3. The frequency of adverse effects was 31% (4/13), but only the treatment was withdrawn in 1 patient (8%). Three patients presented digestive discomfort that forced to reduce the dose of the antifibrotic. One patient developed a toxic hepatitis due to nintedanib after 4 months of treatment that forced the withdrawal of the drug, replacing it 1 month ago with pifernidone. None of the patients died during the follow-up period. <h3>Conclusion:</h3> Our data provides evidence of the safety and tolerability of both pirfenidone and nintedanib in patients with DIDL-SAD refractory to GC and immunosuppressant therapy. <h3>Disclosure of Interests:</h3> Marta Aguilar-Zamora: None declared, J. Narváez Consultant for: Bristol-Myers Squibb, Juanjo J Alegre-Sancho: None declared, Vanesa Vicens: None declared, Maria Molina: None declared, Joan Miquel Nolla: None declared