Experience with the Compassionate Use Program of nintedanib for the treatment of Idiopathic Pulmonary Fibrosis in Argentina

ABSTRACT

Introduction: Idiopathic Pulmonary Fibrosis (IPF) is a diffuse lung disease (DLD) of unknown etiology that is chronic and progressive. It occurs in older adults; it is restricted to the lungs and it is associated with the anatomopathological and/or tomographic pattern of Usual Interstitial Pneumonia (UIP). The evolution of the disease is progressive and it is associated with a mean 5-year survival rate of 20%. Objectives: to identify the clinical and pulmonary function characteristics in the group of patients with IPF included in the Compassionate Use Program (NPU, Named Patient Use); to identify the safety profile reported with nintedanib. Materials and methods: a retrospective, descriptive and cross-sectional study including 54 patients enrolled in the NPU program from September 1st, 2015 to August 10th, 2016. Data were collected from the NPU program records. Results: fifty-four patients with IPF were included in the NPU program, of whom 47 received nintedanib; the data from the latter were analyzed. Thirty-seven (78.72%) were males, with a mean age at the beginning of treatment of 67.47 ± 7.85 years, and in 9 cases (19.14%) the diagnosis was confirmed by lung biopsy. The mean forced vital capacity (FVC) at the beginning of treatment was 65.87±19.23 and it is presented as the percentage of the predictive value; the mean carbon dioxide diffusing capacity (DLCO) presented as the percentage of the predictive value was 38.74 ± 3.09. The time of progression from the diagnosis of IPF to the beginning of the treatment with nintedanib was 27.17± 27.9 months (median 17). Average drug exposure to cut-off point was 9.92 weeks ± 2.15 (median 10 weeks). In 7 cases (31.91%) the FVC was over 80%, in 22 (46.80%) cases it was between 50 and 79% and in 10 cases (21.27%) it was below 49%. In total, 7 patients (14.89%) exhibited adverse events Five (10.6%) patients exhibited weight loss, 4 (8.51%) diarrhea, 2 patients had nausea, 1 (2.12%) an increase of the liver enzymes and 1 (2.12%) pruritus. In most cases, the adverse events appeared during the first 2 weeks after beginning the treatment with nintedanib. In 3 (6.38%) cases it was imperative to suspend nintedanib permanently due to the adverse effects and in 4 (8.51%) cases the dose had to be titrated to 100 mg every 12 hours. Out of the total of patients, 6 (12.76%) passed away due to the progression of their underlying disease. Conclusions: such as it was reported by other groups, nintedanib has a manageable and tolerable safety profile. In our series of 47 patients with IPF who received at least one dose of nintedanib, 14.89% had an adverse event that led to the permanent discontinuation of the drug in only 3 patients (6.38%).