Pneumologie 2020; 74(S 01): 106
DOI: 10.1055/s-0039-3403296
Posterbegehung (PO20) – Sektion Klinische Pneumologie
Fortschritte bei Lungenfibrosen 2020
Georg Thieme Verlag KG Stuttgart · New York

Does brain natriuretic peptide (BNP) at baseline influence the effects of nintedanib plus sildenafil in patients with IPF?

J Behr
1   Medizinische Klinik und Poliklinik V, University of Munich and Asklepios Klinik München-Gauting, Member of the German Centre for Lung Research, Germany
,
M Kolb
2   Mcmaster University and St. Josephʼs Healthcare, Hamilton, Ontario, Canada
,
H Olschewski
3   Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria and Division of Pulmonology, Medical University of Graz, Graz, Austria
,
JW Song
4   Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
,
F Luppi
5   University of Milan Bicocca, San Gerardo Hospital, Asst Monza, Italy
,
B Schinzel
6   Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany
,
S Stowasser
6   Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany
,
M Quaresma
6   Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany
,
FJ Martinez
7   Weill Cornell Medicine, New York, USA
› Author Affiliations
Further Information

Publication History

Publication Date:
28 February 2020 (online)

Also available at
 
 

    Introduction: In the INSTAGE trial in patients with IPF and DLco ≤ 35% predicted, nintedanib plus sildenafil was not associated with a significant benefit on SGRQ total score (primary endpoint) vs. nintedanib alone. However, nintedanib plus sildenafil was associated with stabilisation in BNP, a marker of right ventricular strain, and reduced decline in FVC vs. nintedanib alone.

    Aim: To assess whether baseline BNP influenced the effects of nintedanib plus sildenafil vs. nintedanib alone.

    Methods: In post-hoc analyses, patients with baseline BNP ≤ vs. > median were compared on changes from baseline in BNP at week 24 and in SGRQ total score and FVC at weeks 12 and 24; time to absolute FVC ≥ 5% predicted or death; and time to relative FVC decline ≥ 10% predicted or death.

    Results: At baseline, median BNP was 52 ng/L; 140 patients had BNP ≤ 52 ng/L and 133 had BNP > 52 ng/L. All endpoints showed numerical benefits of nintedanib plus sildenafil vs. nintedanib alone in both subgroups. Compared with patients with baseline BNP below the median, the combination provided a significantly greater benefit on BNP levels and a numerical benefit on FVC in patients with higher baseline BNP.

    Conclusions: In patients with IPF and severely impaired gas exchange, the benefit of nintedanib plus sildenafil vs. nintedanib alone on changes in BNP and FVC seemed more pronounced in patients with baseline BNP above the median.

    Table 1 

    Baseline BNP ≤ 52 ng/L

    Baseline BNP > 52 ng/L

    Treatment-by-subgroup-by-time interaction p-value

    Nintedanib + sildenafil

    Nintedanib alone

    Difference (95% CI)

    Nintedanib + sildenafil

    Nintedanib alone

    Difference (95% CI)

    * These between-group comparisons are expressed as hazard ratios.

    Mean (SE) change in BNP at week 24, ng/L

    − 5.44 (15.83)

    − 0.72 (17.95)

    − 4.72 (− 50.92, 41.48)

    − 20.41 (19.34)

    72.97 (16.33)

    − 93.38 (− 142.11, − 44.65)

    0.0101

    SGRQ total score

    Mean (SE) change at week 12

    − 1.05 (1.32)

    − 0.54 (1.53)

    − 0.50 (− 4.48, 3.47)

    − 1.62 (1.61)

    − 0.93 (1.37)

    − 0.69 (− 4.84, 3.46)

    0.9501

    Mean (SE) change at week 24

    0.32 (1.47)

    3.18 (1.71)

    − 2.86 (− 7.31, 1.59)

    0.14 (1.87)

    1.77 (1.60)

    − 1.64 (− 6.47, 3.19)

    0.7146

    FVC, mL

    Mean (SE) change at week 12

    − 18.6 (20.6)

    − 41.8 (23.6)

    23.2 (− 38.5, 84.8)

    46.3 (25.0)

    − 13.7 (21.2)

    60.0 (− 4.3, 124.3)

    0.4157

    Mean (SE) change at week 24

    − 68.5 (24.8)

    − 75.8 (28.6)

    7.3 (− 67.2, 81.8)

    55.3 (30.8)

    − 45.6 (26.3)

    100.9 (21.4, 180.5)

    0.0917

    Rate of change in FVC, mL/24 weeks

    − 65.7 (23.3)

    − 83.1 (26.5)

    17.4 (− 52.7, 87.4)

    46.7 (32.7)

    − 51.6 (27.9)

    98.3 (12.9, 183.8)

    0.1450

    n (%) with absolute FVC decline ≥ 5% predicted or death

    26 (32.9)

    36 (59.0)

    0.48 (0.29, 0.80)*

    17 (29.3)

    33 (44.0)

    0.65 (0.35, 1.18)*

    0.3843

    n (%) with relative FVC decline ≥ 10% predicted or death

    22 (27.8)

    22 (36.1)

    0.72 (0.39, 1.30)*

    13 (22.4)

    28 (37.3)

    0.63 (0.32, 1.21)*

    0.8018

    * presented at ERS 2019, ‡ presenting on behalf of the authors


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