Pneumologie 2020; 74(S 01): 58
DOI: 10.1055/s-0039-3403187
Posterbegehung (PO10) – Sektion Klinische Pneumologie
Therapiefortschritte bei Kollagenose-assoziierten ILDs & pulmonaler Hypertonie
Georg Thieme Verlag KG Stuttgart · New York

Effects of nintedanib in patients with systemic sclerosis-associated ILD (SSc-ILD) and differing extents of lung fibrosis: the SENSCIS trial*

R Wiewrodt
1   Pulmonary Division, Dpt. of Medicine A, University Hospital Muenster, Muenster, Germany
,
G Raghu
2   University of Washington, Seattle, USA
,
O Distler
3   Department of Rheumatology, University Hospital Zurich, Zurich, Switzerland
,
A Azuma
4   Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
,
KB Highland
5   Respiratory Institute, Cleveland Clinic, Cleveland, Ohio, USA
,
M Kuwana
6   Department of Allergy and Rheumatology, Nippon Medical School Graduate School of Medicine, Tokyo, Japan
,
MD Mayes
7   Division of Rheumatology and Clinical Immunogenetics, University of Texas Mcgovern Medical School, Houston, Texas, USA
,
D Wachtlin
8   Boehringer Ingelheim Pharma GmbH & Co. Kg, Ingelheim am Rhein, Germany
,
S Stowasser
9   Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany
,
M Alves
9   Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany
,
M Gahlemann
10   Boehringer Ingelheim (Schweiz) GmbH, Basel, Switzerland
,
TM Maher
11   National Heart and Lung Institute, Imperial College London, Uk; National Institute for Health Research Clinical Research Facility, Royal Brompton Hospital, London, UK
› Author Affiliations
Further Information

Publication History

Publication Date:
28 February 2020 (online)

Also available at
 

Background: In the SENSCIS trial in patients with SSc-ILD, nintedanib reduced the annual rate of FVC decline (mL/year) vs. placebo (primary endpoint). There was no significant difference between groups in change in modified Rodnan skin score (mRSS) or St Georgeʼs Respiratory Questionnaire (SGRQ) total score (key secondary endpoints) at week 52.

Aim: Assess whether extent of lung fibrosis influenced the efficacy of nintedanib.

Methods: Subjects with SSc-ILD, ≥ 10% fibrosis of the lungs on HRCT and FVC ≥ 40% predicted were randomised to nintedanib 150 mg bid or placebo. We analysed primary and key secondary endpoints in subgroups with extent of lung fibrosis < 20% vs. ≥ 20% at baseline.

Results: Mean ± SD extent of fibrosis at baseline was 36.8 ± 21.8% in the nintedanib group (n = 288) and 35.2 ± 20.7% in the placebo group (n = 288); 80.2% and 74.3% of subjects in these groups, respectively, had ≥ 20% fibrosis. The effect of nintedanib on FVC decline was numerically more pronounced in subjects with ≥ 20% fibrosis, but the treatment-by-time-by-subgroup interaction did not reach statistical significance. A more pronounced increase in SGRQ total score with nintedanib vs. placebo was observed in patients with < 20% fibrosis. Changes in mRSS were similar in both subgroups.

Conclusion: Nintedanib reduced ILD progression in patients with SSc-ILD irrespective of extent of lung fibrosis at baseline.

Table 1 

Extent of lung fibrosis < 20% at baseline

Extent of lung fibrosis ≥ 20% at baseline

Nintedanib (n = 57)

Placebo (n = 74)

Nintedanib (n = 231)

Placebo (n = 214)

Not all patients provided data for all endpoints. * Analyzed using a random coefficient regression model (with random slopes and intercepts) including anti-topoisomerase I antibody (ATA) status, age, height, gender and baseline FVC as covariates, and baseline-by-time, treatment-by-subgroup and treatment-by-subgroup-by-time interaction terms. ** Analyzed using a mixed model repeated measures approach with terms for ATA status, visit, baseline FVC and treatment-by-subgroup-by-visit interaction.

Annual rate (SE) of decline in FVC (mL/year)*

− 69.3 (31.2)

− 85.5 (26.7)

− 48.2 (15.5)

− 96.1 (15.8)

  • Adjusted difference vs. placebo (95% CI)

16.2 (− 64.1, 96.5)

47.9 (4.5, 91.3)

  • Treatment-by-time-by-subgroup interaction

p = 0.50

Absolute change from baseline in mRSS at week 52, mean (SE)**

− 0.9 (0.6)

− 1.7 (0.5)

− 2.5 (0.3)

− 2.0 (0.3)

  • Adjusted difference vs. placebo (95% CI)

0.8 (− 0.7, 2.4)

− 0.5 (− 1.3, 0.4)

  • Treatment-by-visit-by-subgroup interaction

p = 0.15

Absolute change from baseline in SGRQ total score at week 52, mean (SE)**

3.4 (2.0)

− 3.2 (1.7)

0.2 (1.0)

− 0.1 (1.0)

  • Adjusted difference vs. placebo (95% CI)

6.6 (1.4, 11.7)

0.3 (− 2.5, 3.0)

  • Treatment-by-visit-by-subgroup interaction

p = 0.04

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