LAUSR

Introduction In 2015 nintedanib became available on a compassionate use programme (CUP) to patients with idiopathic pulmonary fibrosis (IPF), after the 2014 publication of the INPULSIS trial1 and before receiving National Institute for Health and Care Excellence (NICE) approval in England and Wales in January 2016.2 NICE subsequently approved nintedanib with the same limited forced vital capacity (FVC) criteria as for pirfenidone: 50–80% predicted (pred). The nintedanib CUP allowed patients with FVC >80% pred to receive anti-fibrotic treatment, and many have continued to take nintedanib for over 4 years. We have reviewed our single centre cohort of real-life IPF patients and examined outcomes. Methods We retrospectively identified patients who consented to receive nintedanib under the CUP from 1st February 2015 and who had more than one FVC recorded. We obtained demographic, lung function and mortality data from the electronic medical record. We collected data to 1st June 2019. We compared CUP patients to the patients in the INPULSIS trial (1) performing statistics using GraphPad Prism. Results Our patients were older, had higher baseline FVC measurements and were followed for longer, but had greater reductions in lung function over time (table 1). Six of 23 (26%) patients died over a 52 month period in our observational study compared to 35 out of 638 (5.5%) over 12 months in INPULSIS 1 and 2 combined.1 Discussion We studied real-life IPF patients who tended to be older than in the pivotal regulatory clinical trial.(1) Direct statistical comparisons were not possible without the raw data but baseline absolute FVC values were similar. However, our patients represent earlier or milder disease: 74% would not have qualified for nintedanib on NICE criteria. These data provide insights into treatment of older and high FVC patients with nintedanib. References Richeldi L, et al. NEJM. 2014;370(22):2071–82. NICE Technology Appraisal Guidance (TA379). 2016.Abstract M12 Table 1 Nintedanib compassionate use programme patient demographics and outcomes compared to INPULSIS-1 trial patients Nintedanib compassionate use programme (52 months observation) INPULSIS-1 nintedanib group (1) (12 months study) Number of patients 23 309 Number of males/ females 19/4 83% male 251/58 81% male Age at baseline in years (y) 1 73.5 SD 6.7 66.9 SD 8.4 Ethnicity White European/ other 17/6 74% White European 198/111 64% White European Mean FVC at baseline (ml) 2792 SD 1241 2757 SD 735 Mean FVC at last measure before 1/6/19 (ml) 2427 SD 1224 Mean FVC% predicted at baseline 91.5 SD 25.1 79.5 SD 17.0 Mean difference FVC over total FU period (ml) -443 SD 470 Total follow up period first FVC to last FVC in months 31 SD 14 12 Fixed follow up 1 year Rate of change of FVC (ml per year) from baseline to date of last FVC -253 SD 372 -95 95% confidence interval Mean difference in FVC as% change from baseline -16.4 SD 14.7 Mean% change per year compared with baseline -10.1 SD 14.4 Eligible for anti-fibrotics via NICE ie FVC 50 –80 % pred 4 26% Number FVC > 80% pred 17 74% Number with FVC > 90% pred 15 65% Number with FVC > 100% pred 7 30% Number with FVC < 50% pred 2 9% Excluded from trials Mean number of months on nintedanib 30.4 SD 16.2 10.3 SD 3.4 Number still on nintedanib at end of study (1/6/2019 for compassionate use patients and 12 months for trial patients) 2 10 43% 231 75% Number of responders (where FVC did not fall > 10% of baseline per year) 14 61% 447/634 71% INPULSIS-1 and 2 combined Number progressing on treatment (FVC drop > 10% per year) 9 39% 31 10% Key: FVC=forced vital capacity;%=percentage; pred=predicted; ml=millilitres; SD=standard deviation; Baseline=First lung function after 1/2/2015 and before drug started 1 Ages: 4 over 80, 10 over 75, 15 over 70 y. 2 13 stopped: 5 stopped for GI reasons, 2 died on drug, 1 had PE, 2 patient choice, 2 lost to FU, 1 progressed on treatment