Insights from the German Compassionate Use Program of Nintedanib for the Treatment of Idiopathic Pulmonary Fibrosis

Abstract

Background: Nintedanib is approved for the treatment of idiopathic pulmonary fibrosis (IPF) and has been shown to slow disease progression by reducing annual lung function decline. Objective: To evaluate the results of a large cohort of IPF patients treated with nintedanib within a compassionate use program (CUP) in Germany (9 centers). Methods: Patients (≥40 years) were required to have a confirmed diagnosis of IPF, a forced vital capacity (FVC) ≥50% predicted (pred.) and a carbon monoxide diffusing capacity (D<smlcap>LCO</smlcap>) 30-79% pred. and not to be eligible for pirfenidone treatment. Clinical data, pulmonary function tests and adverse events were recorded up to July 2015. Results: Sixty-two patients (48 male/14 female) with moderate IPF (FVC 64 ± 17% pred. and D<smlcap>LCO</smlcap> 40 ± 10% pred.) were treated with nintedanib. 77% of patients switched from pirfenidone (mean treatment duration 14 ± 2 months) mostly due to disease progression (mean decline in FVC 7.4 ± 3% pred. in the 6 months prior to nintedanib intake). Initiation of nintedanib treatment occurred 69 ± 29 months after IPF diagnosis, and mean treatment duration was 8 ± 4 months. Most patients (63%) stabilized 6 months after treatment start (mean FVC decline 3 ± 1 vs. -17 ± 2% in patients with disease progression; p < 0.01). The most common adverse events were diarrhea (63%) and weight loss (50%). Dose reduction occurred in 34% of cases and treatment discontinuation in 10%. Conclusion: Nintedanib treatment was generally well tolerated and was associated with FVC stabilization in the majority of IPF patients in this CUP setting where most patients were not treatment naïve. Our data are in agreement with the previously published data.

Real-World Experience with Nintedanib in Patients with Idiopathic Pulmonary Fibrosis

“…The demographic characteristics of the patients reported in this study, including age, sex distribution, and smoking history, were broadly similar to those reported in the previous INPULSIS trials [11] as well as to those reported in other real-world reports [15, 16], reflecting the typical patient demographic characteristics of patients with IPF. Subgroup analyses of the INPULSIS trials have shown that the treatment effects of nintedanib are consistent across patient subgroups, including sex, age, smoking status, and baseline respiratory functions measured using baseline percent predicted FVC [26].…”

“…As such, our data provide support for the benefits of nintedanib in a patient population with more severe disease at baseline; nintedanib treatment was associated with stable disease at 6 months, as measured by FVC, in the majority (67%) of patients. The baseline respiratory function reported in our real-world cohort was similar to that in patients treated in other real-world analyses [15, 16]. …”

“…Acute exacerbations of IPF were more commonly reported in our cohort (17%) than previously reported with nintedanib treatment in either the German compassionate use programme (11%) [15], the INPULSIS studies (5%) [12], or the ranges typically reported in treated and untreated patient populations (8–15%) [26]. The increased rate of acute exacerbations reported here is most probably the results of more advanced disease in our patient population than in previous studies, as indicated by a longer time since first diagnosis (33 months).…”

“…Results recently published in abstract form from the ongoing INPULSIS®-ON extension study have confirmed the long-term benefit of nintedanib in reducing disease progression and the long-term safety and tolerability profile of nintedanib in patients suffering from IPF [14]. Only minimal data of patients treated in the real-world setting have been published so far and include data from a cohort of 62 patients treated with nintedanib as part of the German compassionate use programme with a mean treatment duration 14 months [15] and data from a cohort of 124 patients treated with nintedanib in the UK in which the average length of treatment was around 9 months [16]. These findings confirmed the results of controlled trials.…”

Year in review 2016: Interstitial lung disease, pulmonary vascular disease, pulmonary function, paediatric lung disease, cystic fibrosis and sleep

“…14,15 In the recent review by Borie et al, the authors highlight the myriad of unanswered questions with regard to anti-fibrotic therapy including when treatment should be stopped and how treatment failure is defined.…”