Pneumologie 2020; 74(S 01): 59
DOI: 10.1055/s-0039-3403188
Posterbegehung (PO10) – Sektion Klinische Pneumologie
Therapiefortschritte bei Kollagenose-assoziierten ILDs & pulmonaler Hypertonie
Georg Thieme Verlag KG Stuttgart · New York

Efficacy and Safety of Nintedanib in Patients with Systemic Sclerosis-Associated Interstitial Lung Disease: Subgroup Analysis of the SENSCIS Trial by Corticosteroid Use*

R Wiewrodt
1   Pulmonary Division, Dpt. of Medicine A, University Hospital Muenster, Muenster, Germany
,
M Vonk
2   Department of Rheumatology, Radboud University Medical Center, Nijmegen, The Netherlands
,
O Distler
3   Department of Rheumatology, University Hospital Zurich, Zurich, Switzerland
,
D Furst
4   Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles, California, USA
,
E Hachulla
5   Department of Internal Medicine and Clinical Immunology, Hôpital Claude Huriez, University of Lille, Lille, France
,
S Johnson
6   Toronto Scleroderma Program, Department of Medicine, Toronto Western and Mount Sinai Hospitals, University of Toronto, Toronto, Canada
,
S Assassi
7   Department of Rheumatology and Clinical Immunogenetics, Mcgovern Medical School, University of Texas, Houston, Texas, USA
,
L Meng
8   Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut, USA
,
M Quaresma
9   Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany
,
M Alves
9   Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany
,
E Clerisme-Beaty
9   Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany
,
WA Wuyts
10   Unit for Interstitial Lung Diseases, Department of Respiratory Medicine, University Hospitals Leuven, Leuven, Belgium
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Publikationsverlauf

Publikationsdatum:
28. Februar 2020 (online)

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Background/purpose: Nintedanib reduced the rate of decline in FVC over 52 weeks compared with placebo (− 52.4 versus − 93.3 mL/year; difference 41.0 mL/year [95% CI 2.9, 79.0]; p = 0.04) in the SENSCIS trial in SSC-ILD, with manageable adverse events (AEs). Corticosteroids (CS) are commonly used in SSc-ILD, despite a lack of evidence of efficacy. We assessed the efficacy and safety of nintedanib in patients who did/did not use CS in the SENSCIS trial.

Methods: Patients with SSc-ILD with ≥ 10% fibrosis of the lungs on HRCT were randomized to nintedanib 150 mg bid or placebo (prednisone ≤ 10 mg/day or equivalent were allowed). Lung function outcomes and AEs (irrespective of causality) were analyzed.

Results: Of 576 patients who received trial drug, 206 (71.5%) and 191 (66.3%) with nintedanib and placebo, respectively, used CS. Mean (SD) FVC (mL) at baseline was 2499 (814) in patients who used CS, 2501 (691) in patients who did not, and FVC % predicted was 71.9 (17.0) and 73.8 (15.9). With placebo, the mean (SE) rate of decline in FVC over 52 weeks was numerically greater in patients who used CS than in those who did not [− 103.9 (16.7) versus − 72.5 (23.3) mL/year]. Nintedanib reduced the annual rate of decline in FVC (mL/year) versus placebo in both groups (treatment-by-time-by-subgroup interaction p = 0.82) ([Fig. 1]). In the nintedanib and placebo groups, respectively, absolute declines in FVC > 5% predicted were seen in 22.4% and 27.2% of patients who used CS (OR 0.78 [95% CI: 0.49, 1.23]) and 15.9% and 30.9% of patients who did not (OR 0.42 [95% CI: 0.20, 0.87]) (treatment-by-subgroup interaction p = 0.16). The AE profile of nintedanib was similar between the subgroups by CS use, but the proportions of patients with nausea or vomiting AEs were lower, and the proportion with upper respiratory tract infection was higher, in those who used CS ([Table 1]). The proportion of patients treated with nintedanib who had AEs leading to discontinuation of study drug was similar in patients who did and did not use CS (limitation of the analyses: no adjustment for differences in CS use at baseline).

Zoom Image
Fig. 1 Annual rate of decline in FVC (mL/year) over 52 weeks in the SENSCIS trial in subgroups by use of corticosteroids.

Table 1 Adverse events by corticosteroid use in the SENSCIS trial.

Used corticosteroids

Did not use corticosteroids

Nintedanib (n = 206)

Placebo (n = 191)

Nintedanib (n = 82)

Placebo (n = 97)

Adverse events reported over 52 weeks (or until 28 days after last trial drug intake for patients who discontinued trial drug before week 52). Data are n (%) of patients with ≥ 1 such adverse event. Adverse events were coded according to preferred terms in the Medical Dictionary for Regulatory Activities (MedDRA). *Adverse events reported in > 10% of patients in any of the subgroups shown.

Most frequent adverse events*

  • Diarrhea

159 (77.2)

64 (33.5)

59 (72.0)

27 (27.8)

  • Nausea

59 (28.6)

27 (14.1)

32 (39.0)

12 (12.4)

  • Vomiting

45 (21.8)

21 (11.0)

26 (31.7)

9 (9.3)

  • Skin ulcer

42 (20.4)

38 (19.9)

11 (13.4)

12 (12.4)

  • Nasopharyngitis

27 (13.1)

33 (17.3)

9 (11.0)

16 (16.5)

  • Cough

27 (13.1)

35 (18.3)

7 (8.5)

17 (17.5)

  • Weight decreased

23 (11.2)

9 (4.7)

11 (13.4)

3 (3.1)

  • Upper respiratory tract infection

28 (13.6)

27 (14.1)

5 (6.1)

8 (8.2)

  • Abdominal pain

26 (12.6)

13 (6.8)

7 (8.5)

8 (8.2)

  • Fatigue

23 (11.2)

16 (8.4)

8 (9.8)

4 (4.1)

  • Decreased appetite

18 (8.7)

8 (4.2)

9 (11.0)

4 (4.1)

Adverse events leading to treatment discontinuation

31 (15.0)

15 (7.9)

15 (18.3)

10 (10.3)

Conclusion: In the SENSCIS trial in patients with SSc-ILD, over two-thirds of patients used CS. Nintedanib reduced the annual rate of decline in FVC irrespective of use of CS. The AE profile of nintedanib was similar in patients who did and did not use CS.

* presented at ACR 2019