Prospective observational investigation of possible correlations between change in FVC and change in cough or dyspnea scores using the living with pulmonary fibrosis questionnaire (L-PF) between baseline and after approximately 52 weeks of nintedanib treatment in patients suffering from chronic fibrosing ILD with a progressive phenotype. (INREAL)

Study type

• Study topic:
  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Drug utilisation

  Effectiveness study (incl. comparative)
• Data collection methods:
  Primary data collection

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Name of medicine:
  OFEV
• Study drug International non-proprietary name (INN) or common name:
  NINTEDANIB
• Anatomical Therapeutic Chemical (ATC) code:
  (L01EX09) nintedanib

  nintedanib
• Medical condition to be studied:
  Interstitial lung disease
• Additional medical condition(s):
  PF-ILD

Population studied

• Short description of the study population:
  patients suffering from chronic fibrosing ILD with a progressive phenotype
• Age groups:
  Adults (18 to < 46 years)

  Adults (46 to < 65 years)

  Adults (65 to < 75 years)

  Adults (75 to < 85 years)

  Adults (85 years and over)
• Estimated number of subjects:
  100

Study design details

• Study design:
  Single-arm, open-label observational cohort study according to §4, section 23 and §67, section 6 German Medicines Act
• Main study objective:
  The primary objective is to investigate changes in dyspnea or cough as measured with the L-PF questionnaire over 52 weeks of nintedanib treatment in patients suffering from chronic fibrosing ILD with a progressive phenotype (excluding IPF), including a snapshot-analysis before LPI, to evaluate a possible correlation between changes in FVC and L-PF (dyspnea and cough).
• Setting:
  Data of 100 patients suffering from chronic fibrosing ILD with a progressive phenotype treated with nintedanib in routine suffering from chronic fibrosing ILD with a progressive phenotype practice are planned to be recruited for this NIS by about 20 specialists, experienced in treating ILD patients, (e. g., pulmonologists and rheumatologists) throughout Germany.
• Outcomes:
  Correlation between change from baseline to week 52 in FVC % pred. and change from baseline to week 52 in dyspnea symptom score Correlation between change from baseline to week 52 in FVC % pred. and change from baseline to week 52 in cough symptom score, Correlation between change from baseline to week 52 in FVC mL and change from baseline to week 52 in dyspnea symptom score Correlation between change from baseline to week 52 in FVC mL and change from baseline to week 52 in cough symptom score Absolute change from baseline in L-PF cough symptom score at week 52 Absolute change from baseline in L-PF dyspnea symptom score at week 52
• Data analysis plan:
  All patients having received at least one dose of nintedanib will be included in the treated set. All analyses will be performed on the treated set. For the analysis of the primary and secondary outcomes related to correlations, Pearson measures of correlation along with 95% two-sided confidence intervals and the two-sided p-values will be provided. The secondary outcomes related to absolute changes will be analysed using a restricted maximum likelihood (REML) based repeated measures approach. Analyses will include the fixed, categorical effect of visit, as well as the continuous, fixed covariates of baseline and baseline-by-visit interaction. An unstructured (co)variance structure will be used to model the within-patient measurements. Time to event endpoints over the whole trial will be analysed in a descriptive manner. Frequency tables and Kaplan-Meier plots will be produced. Further continuous and categorical outcomes will be analyzed descriptively. No subgroup analyses are planned.
• Summary results:
  Study population (102 treated patiens (pts.): mean age 70.47 ± 10.74 years, males (62.75%). Race/ethnicity not collected. Former (45.10%) or current (3.92%) smokers. Diagnoses: autoimmune disease associated ILDs (44.12%), IIPs (32.35%), exposure related ILDs (19.61%), sarcoidosis (3.92%).; Baseline mean FVC was 65.18 ± 18.86% pred. and 2296.37 ± 769.77 ml. After 52 weeks of nintedanib treatment, mean FVC was 65.67 ± 19.62% pred. and 2304.79 ± 710.73 ml. Mean dyspnea symptom score was 24.71 ± 18.56 at baseline and after 52 weeks of treatment, the score was 27.32 ± 21.67. Mean cough symptom score was 37.46 ± 25.67 at baseline and 36.85 ± 28.59 after 52 weeks of treatment.; Due to missing patient questionnaires or other necessary variables for 64 out of all 102 patients, the primary outcome was analyzed for a total of 38 patients. For the primary outcome, the correlation between change in FVC [% pred.] and change in dyspnea symptom score, the Pearson correlation coefficient was -0.26 and the p-value was 0.12 (95% CI -0.53 to 0.07). For the correlation between change in FVC [% predicted] and change in cough symptom score, the Pearson correlation coefficient was -0.11 and the p-value was 0.51 (95% CI -0.41 to 0.22).; For the secondary outcome, the correlation between the change in FVC [ml] and change in dyspnea symptom score, the Pearson correlation coefficient was -0.29 and the p-value was 0.08 (95% CI -0.56 to 0.03). For the correlation between change in FVC [ml] and change in cough symptom score, the Pearson correlation coefficient was -0.16 and the p-value was 0.35 (95% CI -0.45 to 0.17). Absolute change in dyspnea symptom score from baseline to week 52 was 6.75 ± 18.51, and in cough symptom score it was 2.50 ± 24.04.; 69 pts. (67.65%) experienced 139 TEAEs. Overall, 24 STEAEs were reported in 16 pts. (15.69%), 91 TEADRs in 53 patients (51.96%), 3 STEADRs in 3 patients (2.94%), and 4 TEASIs in 3 pts. (2.94%). There were 10 fatal STEAEs among 8 pts. (7.84%).