OP0266 EFFICACY OF NINTEDANIB IN PATIENTS WITH SYSTEMIC SCLEROSIS-ASSOCIATED INTERSTITIAL LUNG DISEASE (SSC-ILD) AND INTERNAL ORGAN INVOLVEMENT: DATA FROM THE SENSCIS TRIAL
Authors: Allanore Y. , Hoffmann-Vold A. M. , Mayes M. , Vonk M. , Miede C. , Alves M. , Riemekasten G. 
Published: May 2021

Background:

SSc is a heterogeneous autoimmune disease characterised by fibrosis of the skin and internal organs. In most patients with SSc-ILD, organs other than the lungs are also affected. In the SENSCIS trial in patients with SSc-ILD, nintedanib reduced the rate of decline in forced vital capacity (FVC) (mL/year) over 52 weeks by 44% versus placebo.

Objectives:

We investigated the extent of organ involvement related to SSc at baseline in patients in the SENSCIS trial and the effect of nintedanib versus placebo on the rate of FVC decline in subgroups by internal organ involvement.

Methods:

The SENSCIS trial enrolled patients with SSc-ILD with first non-Raynaud symptom ≤7 years before screening, extent of fibrotic ILD ≥10% on high-resolution computed tomography (HRCT) and FVC ≥40% predicted. Patients with clinically significant pulmonary hypertension were excluded. Patients were randomised to receive nintedanib or placebo until the last patient reached week 52 but for ≤100 weeks. In post-hoc analyses, we analysed the rate of decline in FVC (mL/year) over 52 weeks in subgroups with and without different types of SSc-related internal organ involvement (upper gastrointestinal; lower gastrointestinal; cardiovascular [CV]; peripheral vascular; muscular; joint). These subgroups were defined based on patients’ SSc-related medical history as reported in the case report form. A random slope and intercept model was used to assess the rate of decline in FVC (mL/year) and an interaction test applied to assess potential heterogeneity in the treatment effect of nintedanib between the subgroups.

Results:

Of 576 patients, 96.9% had peripheral vascular involvement, 75.5% had upper gastrointestinal and 39.8% lower gastrointestinal involvement, 45.7% had CV involvement, 40.6% had joint involvement, and 27.1% had muscular involvement at baseline. In the placebo group, the rate of decline in FVC (mL/year) was numerically greater in patients with than without upper gastrointestinal involvement and in patients without than with joint involvement or muscular involvement (Figure). The exploratory interaction p-values did not indicate heterogeneity in the treatment effect of nintedanib versus placebo on reducing the rate of decline in FVC (mL/year) between the subgroups based on organ involvement (p>0.05 for all treatment-by-time-by-subgroup interactions) (Figure).

Conclusion:

Patients in the SENSCIS trial had diverse complications related to SSc. There was no evidence of a differential treatment effect of nintedanib on reducing the rate of decline in FVC based on gastrointestinal, CV, joint, or muscular involvement at baseline.

Acknowledgements:

The SENSCIS trial was funded by Boehringer Ingelheim. Medical writing support was provided by FleishmanHillard Fishburn, London, UK. The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE).

Disclosure of Interests:

Yannick Allanore Consultant of: Boehringer Ingelheim, Medsenic, Menarini and Sanofi, Grant/research support from: Alpine Pharmaceuticals, Anna-Maria Hoffmann-Vold Speakers bureau: Actelion, Boehringer Ingelheim, Lilly, MSD and Roche, Consultant of: Actelion, ARXX, Bayer, Boehringer Ingelheim, Lilly, Medscape, MSD and Roche, Grant/research support from: Boehringer Ingelheim, Maureen Mayes Consultant of: Paid consultant or member of Advisory Board/Steering Committee for Boehringer Ingelheim, Eicos, Galapagos and Mitsubishi Tanabe Pharma, Grant/research support from: Clinical trial research support from Boehringer Ingelheim, Corbus, Eicos and Galapagos, Madelon Vonk Speakers bureau: Boehringer Ingelheim, GlaxoSmithKline, Janssen and Roche, Consultant of: Boehringer Ingelheim and Janssen, Grant/research support from: Boehringer Ingelheim, Ferrer, Galapagos and Janssen, Corinna Miede Employee of: Currently an employee of mainanalytics GmbH, contracted by Boehringer Ingelheim, Margarida Alves Employee of: Currently an employee of Boehringer Ingelheim, Gabriela Riemekasten Speakers bureau: Actelion, Boehringer Ingelheim, Cellgene, GlaxoSmithKline, Janssen, Novartis and Roche, Consultant of: Actelion, Boehringer Ingelheim and Janssen, Grant/research support from: Janssen