Effects of nintedanib in patients with limited cutaneous systemic sclerosis and interstitial lung disease
Authors: Allanore Yannick , Khanna Dinesh , Smith Vanessa , Aringer Martin , Hoffmann-Vold Anna-Maria , Kuwana Masataka , Merkel Peter A , Stock Christian , Sambevski Steven , Denton Christopher P ,   SENSCIS Trial Investigators, Bergna M , Casado G , Mannucci Walter P , Proudman S , Stevens W , Thakkar V , Troy L , Loeffler-Ragg J , Olschewski H , André B , Bondue B , Houssiau F , Smith V , Wuyts W , Azevedo V , Johnson S , Keystone E , Khalidi N , Levesque M , Rozas R Maturana , Silva Orellana A , Huang C , Li J , Jiang Z , Liu Y , Xiao W , Xu J , Zeng X , Zheng Y , Zou H , Becvar R , Madsen H , Søndergaard K , Kilpeläinen M , Myllärniemi M , Agard C , Allanore Y , Bourdin A , Cottin V , Crestani B , Diot E , Dominique S , Hachulla E , Jouneau S , Leroy S , Nunes H , Prevot G , Wallaert B , Wemeau L , Aringer M , Bewig B , Blaas S , Distler J , Ehrchen J , Ewert R , Gläser S , Henes J , Hunzelmann N , König R , Kötter I , Kreuter M , Prasse A , Schulze-Koops H , Sfikakis P , Vlachoyiannopoulos P , Losonczy G , Behera D , Gayathri Devi H J , Kadel J , Kawedia M , Kumar D , Kumar U , Lokhande R , Malpani A , Mohan M , Nalawade A , Parakh U , Swarnakar R , Shobha V , Thangakunam B , Udwadia Z , Henry M , O'Reilly K , Balbir-Gurman A , Kramer M , Litinsky I , Rosner I , Cutolo M , Gabrielli A , Iaccarino L , Pesci A , Riccieri V , Vettori S , Funakubo Y , Inoue Y , Kawakami A , Kawaguchi Y , Kawamura T , Kondoh Y , Kuwana M , Nanki T , Nishioka Y , Nozawa K , Ogura T , Okamoto M , Sano H , Sasai R , Sasaki N , Suda T , Takahashi H , Takeuchi T , Makino S , Tanaka S , Yamasaki Y , Ch'ng S S , Cheah C , Kan S , Raja Mohamed R B , Selman M , de Vries-Bouwstra J K , van den Toorn L , Vonk M , Voskuyl A E , Hoffmann-Vold A M , Seip M , Dankiewicz-Fares I , Olesiejuk R , Pulka G , Szepietowski J , Alves J , Bernardes M , Cordeiro A , Costa J , Neves S , Salvador M J , Alegre Sancho J , Carreira Delgado P , Castellví Barranco I , Cifrián Martínez J , Guillén del Castillo A , Ovalles J G , López-Longo F J , Rivera Gallego A , Freire Dapena M C , Román Ivorra J A , Ekwall A-K H , Maurer B , Mihai C M , Müller R , Mahakkanukrauh A , Nantiruj K , Siripaitoon B , Denton C P , Herrick A , Madhok R , Maher T M , West A , Antin-Ozerkis D , Bascom R , Criner G , Csuka M E , Dematte D'Amico J , Ettinger N , Fischer A , Gerbino A , Gerke A , Glassberg M , Glazer C , Golden J , Gripaldo R , Gupta N , Hamblin M , Highland K , Ho L , Huggins J T , Hummers L , Jones L , Kahaleh M , Khanna D , Kim H , Lancaster L H , Luckhardt T , Mayes M , Mendoza Ballesteros F , Mooney J , Mohabir P , Morrissey B , Moua T , Padilla M , Patel N , Perez R , Roman J , Rossman M , Russell T , Saketkoo L , Shah A , Shlobin O , Scholand M B , Simms R , Spiera R , Steen V , Veeraraghavan S , Weigt S 
Published: June 2023

Abstract

Objectives
To investigate the course of interstitial lung disease (ILD) and the effects of nintedanib in patients with limited cutaneous systemic sclerosis (lcSSc).

Methods
In the SENSCIS trial, patients with SSc-ILD were randomized to receive nintedanib or placebo. Patients who completed the SENSCIS trial were eligible to enter SENSCIS-ON, in which all patients received open-label nintedanib.

Results
Among 277 patients with lcSSc treated in the SENSCIS trial, the rate (s.e.) of decline in forced vital capacity (FVC; ml/year) over 52 weeks was −74.5 (19.2) in the placebo group and −49.1 (19.8) in the nintedanib group (difference: 25.3 [95% CI −28.9, 79.6]). Among 249 patients with data at week 52, mean (s.e.) change in FVC at week 52 was −86.4 (21.1) ml in the placebo group and −39.1 (22.2) ml in the nintedanib group. Among 183 patients with lcSSc who participated in SENSCIS-ON and had data at week 52, mean (s.e.) change in FVC from baseline to week 52 of SENSCIS-ON was −41.5 (24.0) ml in patients who took placebo in the SENSCIS trial and initiated nintedanib in SENSCIS-ON and −45.1 (19.1) ml in patients who took nintedanib in the SENSCIS trial and continued it in SENSCIS-ON.

Conclusion
Patients with lcSSc may develop progressive fibrosing ILD. By targeting pulmonary fibrosis, nintedanib slows decline in lung function in patients with lcSSc and ILD.

Trial registration
ClinicalTrials.gov (https://clinicaltrials.gov), NCT02597933 and NCT03313180