Pneumologie 2020; 74(S 01): 61-62
DOI: 10.1055/s-0039-3403189
Posterbegehung (PO10) – Sektion Klinische Pneumologie
Therapiefortschritte bei Kollagenose-assoziierten ILDs & pulmonaler Hypertonie
Georg Thieme Verlag KG Stuttgart · New York

The INBUILD Trial of Nintedanib in Patients with Progressive Fibrosing Instititial Lung Diseases: Subgroup with Autoimmune Diseases*

F Bonella
1   Interstitial and Rare Lung Disease Unit, Ruhrlandklinik, University Hospital, Duisburg-Essen University, Essen, Germany
,
E Matteson
2   Mayo Clinic College of Medicine and Science, Rochester, Minnesota, USA
,
C Kelly
3   Institute of Cellular Medicine, Newcastle University, Newcastle Upon Tyne, UK
,
JHW Distler
4   University of Erlangen-Nürnberg, Erlangen, Germany
,
A Hoffmann-Vold
5   Oslo University Hospital, Rikshospitalet, Oslo, Norway
,
JR Seibold
6   Scleroderma Research Consultants LLC, Aiken, South Carolina, USA
,
S Mittoo
7   University Health Network, Toronto, Ontario, Canada
,
O Distler
8   University Hospital Zurich, Zurich, Switzerland
,
RG Goeldner
9   Boehringer Ingelheim Pharma GmbH & Co. Kg, Biberach, Germany
,
R Schlenker-Herceg
10   Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Ct, USA
,
S Stowasser
11   Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany
,
M Quaresma
11   Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany
,
KR Flaherty
12   University of Michigan, Ann Arbor, MI, USA
› Author Affiliations
Further Information

Publication History

Publication Date:
28 February 2020 (online)

Also available at
 

Background/Purpose: Some patients with autoimmune disease develop progressive fibrosing interstitial lung disease (ILD) characterized by increasing fibrosis on HRCT, decline in lung function, worsening symptoms and high mortality. Nintedanib, a tyrosine kinase inhibitor, has established efficacy and safety in patients with idiopathic pulmonary fibrosis (IPF) and is an approved treatment for IPF. Nintedanib was shown to reduce the rate of decline in lung function in patients with systemic sclerosis-associated ILD. The efficacy and safety of nintedanib in patients with chronic fibrosing ILDs with a progressive phenotype are being investigated in the INBUILD trial. Here we describe the subgroup of patients with autoimmune disease-related ILDs in this trial.

Methods: Patients with a physician-diagnosed ILD other than IPF were eligible to participate in INBUILD if they had features of diffuse fibrosing lung disease of > 10% on HRCT, FVC ≥ 45% predicted, DLco ≥ 30-<80% predicted, and met ≥ 1 of 4 criteria for ILD progression ([Table 1]) in the 24 months before screening, despite treatment of ILDs in clinical practice as applicable. Patients were randomized to receive nintedanib 150 mg bid or placebo double-blind stratified by HRCT pattern (usual interstitial pneumonia [UIP]-like fibrotic pattern only or other fibrotic patterns). The primary endpoint is the annual rate of decline in FVC (mL/year) assessed over 52 weeks.

Table 1 Baseline characteristics of patients with autoimmune disease-related ILDs in the INBUILD trial.

Characteristics

All autoimmune ILDs (n = 171)

Rheumatoid arthritis-associated ILD (n = 88)

Systemic sclerosis-associated ILD (n = 40)

Mixed connective tissue disease ILD (n = 20)

Other fibrosing autoimmune ILDs (n = 23)

Mean ± SD or n (%) of patients treated with ≥ 1 dose of trial drug. * ≥ 1 category could be ticked. ** Based on criteria used to identify UIP in the INPULSIS trials (N Engl J Med 2014; 370: 2071 – 2082).

Female

91 (53.2)

34 (38.6)

31 (77.5)

16 (80.0)

10 (43.5)

Age, years

64.3 ± 10.6

66.9 ± 9.7

58.6 ± 10.0

64.4 ± 9.3

63.9 ± 12.5

Weight, kg

72.9 ± 16.9

76.8 ± 16.8

64.5 ± 14.6

73.0 ± 18.1

72.5 ± 15.8

Race

  • White

114 (66.7)

63 (71.6)

24 (60.0)

16 (80.0)

11 (47.8)

  • Asian

51 (29.8)

23 (26.1)

14 (35.0)

2 (10.0)

12 (52.2)

  • Other/missing

6 (3.5)

2 (2.3)

2 (5.0)

2 (10.0)

0

Criteria for ILD progression met in 24 months before screening*

Relative decline in FVC ≥ 10% predicted

88 (51.5)

48 (54.5)

20 (50.0)

9 (45.0)

11 (47.8)

Relative decline in FVC ≥ 5 – < 10% predicted and increased extent of fibrotic changes on HRCT

49 (28.7)

22 (25.0)

13 (32.5)

8 (40.0)

6 (26.1)

Relative decline in FVC ≥ 5 – < 10% predicted and worsened respiratory symptoms

27 (15.8)

11 (12.5)

5 (12.5)

7 (35.0)

4 (17.4)

Worsened respiratory symptoms and increased extent of fibrotic changes on HRCT

57 (33.3)

34 (38.6)

13 (32.5)

5 (25.0)

5 (21.7)

FVC % predicted

70.8 ± 14.8

71.4 ± 16.2

69.5 ± 12.6

71.3 ± 12.2

70.4 ± 15.5

DLCO, % predicted

49.1 ± 19.0

47.5 ± 15.6

53.2 ± 26.4

50.7 ± 19.8

46.7 ± 14.1

Usual interstitial pneumonia (UIP)-like fibrotic pattern only** on HRCT

127 (74.3)

77 (87.5)

24 (60.0)

12 (60.0)

14 (60.9)

Results: Of 663 patients in the trial, 171 (25.8%) had autoimmune disease-related ILDs, of which the most common were rheumatoid arthritis-associated ILD (RA-ILD) (n = 88), systemic sclerosis-associated ILD (n = 40), and mixed connective tissue disease ILD (n = 20) ([Table 1]). At baseline, the mean ± SD age of patients with autoimmune ILDs was 64.3 ± 10.6 years, FVC was 70.8 ± 14.8% and DLco 49.1 ± 19.0% predicted; about half had a relative decline in FVC ≥ 10% predicted in the 24 months before screening. 74.3% of patients with autoimmune ILDs had a UIP-like fibrotic pattern only on HRCT. This pattern was most common in patients with RA-ILD (87.5%). The trial is ongoing.

Conclusion: The INBUILD trial will provide insights into the efficacy and safety of nintedanib in patients with progressive fibrosing ILDs, including those with autoimmune diseases. The results will be presented at the conference.

* presented at ACR 2019