Nintedanib in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD): the SENSCIS trial*

Rationale: Systemic sclerosis (SSc) is a rare and heterogeneous autoimmune disease characterised by progressive fibrosis of the skin and internal organs. Interstitial lung disease (ILD) is a common manifestation of SSc, for which there are no approved treatments. Nintedanib is an intracellular inhibitor of tyrosine kinases that reduces disease progression in patients with idiopathic pulmonary fibrosis. Nintedanib has demonstrated antifibrotic effects in the skin and lungs of animal models of SSc. This provides a rationale for the investigation of nintedanib as a potential treatment for SSc-ILD.

Methods: The SENSCIS trial was designed to investigate the efficacy and safety of nintedanib in patients with SSc-ILD. Eligible patients had SSc with onset of first non-Raynaud symptom ≤ 7 years from screening, ILD (≥ 10% fibrosis of the lungs, confirmed by central assessment of chest HRCT), FVC ≥ 40% predicted and DLco 30 – 89% predicted. Patients were randomized to receive nintedanib or placebo, stratified by the presence of anti-topoisomerase I antibody. Patients on stable therapy with mycophenolate or methotrexate for ≥ 6 months prior to randomization and/or taking prednisone ≤ 10 mg/day were allowed to participate. The primary endpoint is the annual rate of decline in FVC (mL/year) assessed over 52 weeks. Key secondary endpoints are absolute changes from baseline in the modified Rodnan skin score and St Georgeʼs Respiratory Questionnaire total score at week 52.

Results: A total of 576 patients were randomized and received ≥ 1 dose of trial medication. Baseline characteristics are shown in [Table 1]. Three-quarters of patients are female. Approximately half (51.7%) have diffuse cutaneous SSc. At baseline, mean (± SD) age was 54.0 ± 12.2 years, FVC was 72.6 ± 16.7% predicted and DLco was 53.0 ± 15.1% predicted. Median time since onset of first non-Raynaud symptom was 3.4 years and median time since diagnosis of SSc-ILD was 2.6 years. Approximately half (48.6%) of patients were taking mycophenolate at baseline.

Table 1 Baseline characteristics of patients in the SENSCIS trial (n = 576).

Data are mean ± standard deviation or n (%) of patients treated with ≥ 1 dose of trial drug unless otherwise indicated. *Data from patients who selected one race. Three patients ticked two boxes. **Corrected for hemoglobin.
Female	433 (75.2)
Age, years	54.0 ± 12.2
BMI, kg/m²	25.8 ± 4.9
Race*
White	387 (67.2)
Asian	143 (24.7)
Black/African American	37 (6.4)
American Indian/Alaska Native/Native Hawaiian/other Pacific islander	6 (1.1)
Type of SSc
Diffuse cutaneous	298 (51.7)
Limited cutaneous	278 (48.3)
Time since onset of first non-Raynaud symptom, years, median (minimum, maximum)	3.4 (0.1, 7.8)
Time since diagnosis of SSc-ILD, years, median (minimum, maximum)	2.6 (0.1, 21.2)
Extent of fibrosis on HRCT, %	36.0 ± 21.3
Reticulation on HRCT	538 (93.4)
Ground glass opacities on HRCT	487 (84.5)
Honeycombing on HRCT	89 (15.5)
FVC, mL	2500 ± 776
FVC, % predicted	72.6 ± 16.7
DLCO, % predicted**	53.0 ± 15.1
Anti-topoisomerase antibody positive	342 (59.4)
Taking mycophenolate	280 (48.6)
Taking methotrexate	37 (6.4)

Conclusion: The SENSCIS trial, the largest randomized controlled trial to be conducted in patients with SSc-ILD, will provide insights into the effects of nintedanib on a number of clinically relevant outcomes. The results of this trial will be presented in 2019.

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