OP0183 EFFICACY AND SAFETY OF RIOCIGUAT IN PATIENTS WITH EARLY DIFFUSE CUTANEOUS SYSTEMIC SCLEROSIS AND INTERSTITIAL LUNG DISEASE (SSC-ILD): RESULTS FROM THE PHASE IIB RISE-SSC STUDY
Authors: Oliver Distler, Yannick Allanore, Christopher Denton, Masataka Kuwana, Marco Matucci-Cerinic, Janet Pope, Janethe de Oliveria Pena, Kaisa Laapas, Zhen Yao, Friederike Behmenburg, Melanie Hemmrich, Dinesh Khanna
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Diffuse cutaneous systemic sclerosis (dcSSc) is an autoimmune connective tissue disease characterised by fibrosis and, in some patients, interstitial lung disease (ILD). Riociguat is a soluble guanylate cyclase (sGC) stimulator with vasoactive, anti-proliferative and anti-fibrotic effects. We hypothesised that riociguat may preserve lung function in patients with dcSSc. <h3>Objectives</h3> To evaluate the effect of riociguat on lung function in patients with early dcSSc from the multicentre, randomised, double-blind, placebo-controlled Phase IIb RISE-SSc study (NCT02283762). <h3>Methods</h3> Patients had dcSSc of duration ≤18 months, modified Rodnan skin score (mRSS) 10–22 units, forced vital capacity (FVC) ≥45% predicted (%pred) and lung diffusion capacity for carbon monoxide (DLCO) ≥40%pred at screening. Patients were randomised to riociguat (n=60) or placebo (n=61) in individually adjusted doses of 0.5 mg up to 2.5 mg tid. The primary endpoint was the change in mRSS from baseline to Week 52. Secondary endpoints included change in FVC%pred from baseline to Week 52. Effects on lung function (FVC%pred) were assessed in the overall population and in post-hoc analyses in patients with FVC%pred 50-75% or medical history of ILD at baseline. Between groups, differences were in least-squares [LS] means. <h3>Results</h3> Although the study did not meet its primary endpoint, there was a reduction in mRSS with riociguat vs placebo (−2.34; 95% CI: −4.99 to 0.30; p=0.08). There were no significant differences between treatment groups in the changes in FVC%pred (−0.20; 95% CI, −3.40 to +3.00; p=0.90) or DLCO%pred (2.01; 95% CI: −4.99 to 6.25; p=0.35) which included all patients irrespective of the presence of SSc-ILD. However, differences between riociguat and placebo were observed when patients with SSc-ILD were analysed: At baseline, 11/60 (18%) patients in the riociguat group and 12/61 (20%) in the placebo group had medical history suggesting ILD (SSc-ILD); 11/60 (18%), and 7/61 (11%), respectively, had restrictive lung disease (FVC%pred 50–75%). Results in subgroups were expressed as within-group mean change (SD). In patients with SSc-ILD, the decline in FVC%pred between baseline and Week 52 was smaller in the riociguat group (–2.7[4.0]) than the placebo group (–8.9[13.1]). The changes in DLCO%pred were –0.11(0.22) and +0.87(0.71), respectively. In patients with restrictive lung disease, FVC%pred decreased by –8.7 (14.0) at Week 52 with placebo but was almost unchanged (+0.7[5.7]) with riociguat. The changes in DLCO%pred were +0.42(0.85) and –0.27(0.39), respectively. Patients with SSc-ILD receiving riociguat had lower incidences of adverse events and serious adverse events [82% (n=9) and 9% (n=1) respectively] compared with placebo [92% (n=11) and 25% (n=3) respectively] with no differences between treatment groups in the incidence of respiratory adverse events. No deaths occurred in the SSc-ILD subgroup, and no new safety signals were observed. <h3>Conclusion</h3> These results suggest that in an exploratory analysis, riociguat may be associated with preservation of lung function and good tolerability in patients with dcSSc and evidence of ILD on medical history. <h3>Acknowledgement</h3> Adelphi Communications Ltd, Bollington, UK provided medical writing support. <h3>Disclosure of Interests</h3> Oliver Distler Grant/research support from: Prof. Distler received research funding from Actelion, Bayer, Boehringer Ingelheim and Mitsubishi Tanabe to investigate potential treatments of scleroderma and its complications, Consultant for: Prof. Distler has/had consultancy relationship within the last 3 years with Actelion, AnaMar, Bayer, Boehringer Ingelheim, ChemomAb, espeRare foundation, Genentech/Roche, GSK, Inventiva, Italfarmaco, iQvia, Lilly, medac, MedImmune, Mitsubishi Tanabe Pharma, Pharmacyclics, Novartis, Pfizer, Sanofi, Serodapharm and UCB in the area of potential treatments of scleroderma and its complications. In addition, he had/has consultancy relationship within the last 3 years with A. Menarini, Amgen, Abbvie, GSK, Mepha, MSD, Pfizer and UCB in the field of arthritides and related disorders, Yannick Allanore Grant/research support from: Inventiva, F Hoffman La-Roche, Sanofi, BMS, Pfizer, Consultant for: Actelion, Bayer, BMS, Boehringer, Roche, Sanofi, Christopher Denton Grant/research support from: GlaxoSmithKline, Inventiva, CSF Behring, Consultant for: Roche-Genentech, Actelion, GlaxoSmithKline, Sanofi Aventis, Inventiva, CSL Behring, Boehringer Ingelheim, Bayer, Masataka Kuwana Grant/research support from: Actelion, Consultant for: Chugai, Reata, GlaxoSmithKline, Bayer, Boehringer-Ingelheim, Corpus, CSL-Berling, Mochida, Speakers bureau: Actelion, Pfizer, Bayer, Nippon Shinyaku, Chugai, Marco Matucci-Cerinic Grant/research support from: Actelion, MSD, Pfizer, BMS, Chemomab, Sanipedia, Speakers bureau: Actelion, BMS; MSD, Janssen, Janet Pope Consultant for: Eli Lilly and Company, Janethe de Oliveria Pena Employee of: Bayer, Kaisa Laapas Employee of: StatFinn Oy, partly insourced to Bayer, Zhen Yao Employee of: Bayer, Friederike Behmenburg Employee of: Bayer AG, Melanie Hemmrich Employee of: Bayer AG, Dinesh Khanna Shareholder of: Eicos Sciences, Inc, Grant/research support from: Bayer, BMS, Pfizer, Horizon, Consultant for: Actelion Acceleron, Arena, Bayer, BI, BMS, CSL Behring, Corbus, Cytori, GSK, Genentech/Roche, Galapagos, Employee of: Elcos Sciences, Inc