Pneumologie 2020; 74(S 01): 57
DOI: 10.1055/s-0039-3403185
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 FVC at baseline: the SENSCIS Trial*

A Prasse
1   Department of Respiratory Medicine, Mhh Hannover Medical School, Hannover, Germany
,
TM Maher
2   National Heart and Lung Institute, Imperial College London, UK and National Institute for Health Research Clinical Research Facility, Royal Brompton Hospital, London, UK
,
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
,
M Alves
9   Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany
,
M Gahlemann
10   Boehringer Ingelheim (Schweiz) GmbH, Basel, Switzerland
,
S Stowasser
9   Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany
,
G Raghu
11   University of Washington, Seattle, USA
› 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 decline in FVC (mL/year) vs. placebo (primary endpoint). There was no significant difference between treatment groups in change from baseline in modified Rodnan skin score (mRSS) or St Georgeʼs Respiratory Questionnaire (SGRQ) total score (key secondary endpoints) at week 52.

Aim: To assess the efficacy of nintedanib in subgroups by FVC % predicted at baseline.

Methods: Subjects with SSc-ILD with ≥ 10% fibrosis of the lungs on HRCT and FVC ≥ 40% predicted were randomised to receive nintedanib 150 mg bid or placebo. We analysed the primary and key secondary endpoints in subgroups by baseline FVC < 80% vs. ≥ 80% predicted.

Results: 201 (69.8%) subjects in the nintedanib group and 196 (68.1%) in the placebo group had FVC < 80% predicted at baseline. The treatment effect of nintedanib vs. placebo on rate of FVC decline was numerically more pronounced in patients with more preserved lung volume, but the treatment-by-time-by-subgroup interaction did not reach statistical significance ([Table 1]). There were no meaningful effects of nintedanib vs. placebo on change from baseline in mRSS and SGRQ total score in either subgroup.

Table 1 

Baseline FVC < 80% predicted

Baseline FVC ≥ 80% predicted

Nintedanib (n = 201)

Placebo (n = 196)

Nintedanib (n = 87)

Placebo (n = 92)

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)*

− 79.1 (17.2)

− 103.7 (16.8)

4.5 (25.8)

− 68.9 (25.4)

Adjusted difference vs. placebo (95% CI)

24.6 (− 21.4, 70.6)

73.4 (6.6, 140.2)

Treatment-by-time-by-subgroup interaction

p = 0.24

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

− 2.4 (0.3)

− 1.8 (0.3)

− 1.7 (0.5)

− 2.2 (0.5)

Adjusted difference vs. placebo (95% CI)

− 0.6 (− 1.5, 0.3)

0.5 (− 0.8, 1.8)

Treatment-by-visit-by-subgroup interaction

p = 0.18

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

0.8 (1.1)

− 0.6 (1.1)

0.9 (1.6)

− 1.5 (1.5)

Adjusted difference vs. placebo (95% CI)

1.4 (− 1.6, 4.4)

2.4 (− 1.9, 6.7)

Treatment-by-visit-by-subgroup interaction

p = 0.70

Conclusion: In patients with SSc-ILD, nintedanib was observed to reduce ILD progression irrespective of FVC % predicted at baseline.

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