Pneumologie 2019; 73(S 01)
DOI: 10.1055/s-0039-1678099
Posterbegehung (P09) – Sektion Klinische Pneumologie
Neue Entwicklungen bei ILD
Georg Thieme Verlag KG Stuttgart · New York

Safety and tolerability of nintedanib in patients with idiopathic pulmonary fibrosis (IPF): pooled data from six clinical trials[*]

DS Koschel
1   Fachkrankenhaus Coswig, Department of Respiratory Medicine, Germany
,
L Lancaster
2   Vanderbilt University Medical Center, Nashville, Tennessee, USA
,
P Hernandez
3   Qeii Health Sciences Centre, Halifax, Nova Scotia, Canada
,
Y Inoue
4   Clinical Research Center, National Hospital Organization Kinki-Chuo Chest Medical Center, Osaka, Japan
,
D Wachtlin
5   Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany
,
L Loaiza
5   Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany
,
CS Conoscenti
6   Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut, USA
,
M Quaresma
7   Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Center for Interstitial and Rare Lung Diseases, Pneumology and Respiratory Care Medicine, Thoraxklinik, University of Heidelberg, Member of the German Center for Lung Research, Germany
,
S Stowasser
5   Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany
,
L Richeldi
8   Università Cattolica del Sacro Cuore, Fondazione Policlinico A. Gemelli, Rome, Italy
› Institutsangaben
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Publikationsdatum:
19. Februar 2019 (online)

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    Rationale Nintedanib is an approved treatment for IPF that slows disease progression by reducing the rate of decline in forced vital capacity. To characterize the safety and tolerability of nintedanib, we analyzed adverse events (AEs) based on pooled data from six clinical IPF trials.

    Methods Data from patients treated with nintedanib 150 mg bid in the 52-week Phase II TOMORROW trial (NCT00514683) and/or open-label extension (NCT01170065), the two 52-week Phase III INPULSIS trials (NCT01335464, NCT01335477) and/or open-label extension INPULSIS-ON (NCT01619085), and a Phase III b trial (placebo-controlled up to 12 months and open-label up to 12 months [NCT01979952]) were pooled. Dose reductions to 100 mg bid and treatment interruptions were allowed to manage AEs. All AEs reported by investigators were coded according to MedDRA. Event rates (ERs) per 100 patient exposure–years were calculated based on AEs with onset within 28 days (14 days in TOMORROW) after the last dose.

    Results In the 1126 patients the mean (SD) exposure to nintedanib was 27.7 (20.5) months, max. 93.1 months. Total exposure was 2599 patient–years. AEs that led to permanent dose reduction and permanent discontinuation of nintedanib were 12.8 and 23.8 events per 100 patient exposure–years. ERs reported in the pooled population were generally lower than in the INPULSIS trials (Table). Diarrhea was the most frequent AE. Diarrhea led to permanent dose reduction and permanent discontinuation of nintedanib in 17.2% and 8.8% of patients, respectively.

    Conclusion Data from the largest set of nintedanib-treated patients with IPF analyzed to date demonstrated that nintedanib had a manageable safety and tolerability profile. Diarrhea was the most frequent AE in patients treated with nintedanib, but was managed without treatment discontinuation in most patients.

    Tab. 1 AE rates per 100 patient exposure–years

    Nintedanib pooled population (n = 1126)

    INPULSIS trials

    Nintedanib (n = 638)

    Placebo (n = 423)

    AE rate > 10 per 100 patient exposure–years pooled. *MedDRA term ‘IPF’, incl. disease worsening/IPF exacerbations.

    Diarrhea

    76.5

    112.6

    25.6

    Nausea

    18.0

    34.9

    7.0

    Nasopharyngitis

    15.1

    19.6

    22.0

    Bronchitis

    14.5

    15.5

    15.0

    Cough

    13.2

    16.1

    16.2

    Progression of IPF*

    12.9

    11.8

    17.7

    Vomiting

    11.2

    17.1

    2.7

    Upper respiratory tract infection

    10.1

    12.1

    13.3

    #

    * *  presented ATS 2018