학술논문

Effect of macitentan on the development of new ischemic digital ulcers in patients with systemic sclerosis: Dual-1 and Dual-2 randomized clinical trials
Document Type
Electronic Resource
Author
Khanna, DineshDenton, Christopher P.Merkel, Peter A.Krieg, Thomas M.Le Brun, Franck OlivierMarr, AngelinaPapadakis, KellyPope, JanetMatucci Cerinic, MarcoFurst, Daniel E.Zochling, JaneStevens, WendyProudman, SusannaFeenstra, JohnYoussef, PeterSoroka, NikolayTyabut, TamaraMikhailova, Elena IvanovnaRashkov, RashoBatalov, AnastaYablanski, KirilKeystone, EdwardJones, NiallDunne, JameMasetto, ArielCalabresse, Renato JiménezCabezas, Pedro Claudio MirandaSilva, Marta Ofelia AlisteSariego, Imgadt Annelise GoeckeEscalente, William José OteroAnić, BranimirKaliterna, Dušanka MartinovićMorović Vergles, JadrankaNovak, SrdanPrus, VišnjaArtuković, MarinkoSoukup, TomaášBečvař, RadimFojtík, ZdeněkMouthon, LucKollert, FlorianRiemekasten, GabrielaLahner, NinaFierlbeck, GerhardAhmadi Simab, KeihanDiehm, CurtSzücs, GabriellaKumánovics, GáborNagy, GyörgyPal, SarvajeetVeeravalli, Sarath Chandra MouliDanda, DebashishFerri, ClodeveoCozzi, FrancoFerraccioli, GianfrancoWiland, PiotrRudnicak, LidiaZwolak, RobertRoszkiewicz, JadwigaOleynikov, ValentinNikulenkova, NatalyaLesnyak, OlgaKaydashev, IgorKurytar, OleksandrPiura, OlenaChopyak, ValentynaChatterjee, SoumyaHsu, VivienHummers, LauraMartin, RichardDomsic, RobynSchiopu, ElenaShanahan, JosephMurphy, Frederik T.Kaine, JeffreyDavis, WilliamGrau, RafaelEimon, AliciaCatoggio, Luis JoseLaborde, Hugo ArmandoCaeiro, FranciscoSavio, Veronica GabrielaAmitrano, Cristina BeatrizVanthuyne, MarieZeng, XioafengZhang, XiaoZhu, PingVelásquez Franco, Carlos JaimeChoueka, Philippe Selim ChalemSanchez, Patricia Julieta VélezHermann, WalterSticherling, MichaelSteinbrink, KerstinHein, RüdigerAschoff, RolandSfikakis, PetroSettas, LukaFraser, AlexanderVeale, DouglaBalbir Gurman, AlexandraLidar, MeravLitinsky, IrenaLevy, YairCarrillo Vazquez, Sandra MiriamRodriguez Reyna, TatianaMedrano Ramirez, GabrielMorales Torres, JorgePacheco Tena, Cesar FranciscoSanchez Ortiz, AdrianaVonk, Madelon C.Stebbings, SimonSolanki, KamalSteele, RichardNg, KristineZubrzycka Sienkiewicz, AnnaBrzosko, MarekSzepietowski, Jacek C.Hrycaj, PawelDa Silva, Ivone Fernandes SantoDos Santos, Lelita Da ConceiçaoCoelho, Paulo Jorge ClementeRios, GrisselChernykh, TatianaGrunina, ElenaStanislav, MarinaAlly, MahmoodKalla, AsgarBirlik, Ahmet MerihKovalenko, VolodymyrPetrov, AndriyShevchuk, SergiyStanislavchuk, MykolaAnderson, MarinaHerrick, ArianeBelch, JillChung, LorindaCsuka, Mary EllenFrech, TracyGoldberg, AvramKahaleh, BasharMayes, Maureen D.Rothfield, NaomiSimms, Robert WilliamSpiera, RobertSteen, VirginaVarga, JohnSikes, DavidDerk, Chris T.Kohen, Michael D.Ferraccioli, Gianfranco (ORCID:0000-0001-6246-2428)
Source
Subject
Administration, Oral
Double-Blind Method
Endothelin-1
Female
Finger
Human
Male
Middle Aged
Outcome Assessment (Health Care)
Pyrimidine
Scleroderma, Systemic
Skin Ulcer
Sulfonamide
Medicine (all)
Settore MED/16 - REUMATOLOGIA
info:eu-repo/semantics/article
Language
Abstract
Importance: Digital ulcers in patients with systemic sclerosis are associated with pain and poor quality of life. Endothelin-1 promotes vasculopathy in systemic sclerosis after macitentan, an endothelin-1 blocker. Objective: To evaluate the efficacy of macitentan in reducing the number of new digital ulcers in patients with systemic sclerosis. Design, Setting, And Participants: Two international, randomized, double-blind, placebo-controlled trials (DUAL-1, DUAL-2) were conducted between January 2012 and February 2014. Participants were patients with systemic sclerosis and active digital ulcers at baseline. Target enrollment for each study was 285 patients. Interventions: Patients were randomized (1:1:1) to receive oral doses of 3 mg of macitentan, 10 mg of macitentan, or placebo once daily and stratified according to number of digital ulcers at baseline (≤3 or >3). Main Outcomes and Measures: The primary outcome for each trialwas the cumulative number of new digital ulcers from baseline to week 16. Treatment effect was expressed as the ratio between treatment groups. Results: In DUAL-1, among 289 randomized patients (mean age 51.2 years; 85.8% women), 226 completed the study. The adjusted mean number of new digital ulcers per patient over 16 weeks was 0.94 in the 3-mg macitentan group (n = 95) and 1.08 in the 10-mg macitentan group (n = 97) compared with 0.85 in the placebo group (n = 97) (absolute difference, 0.09 [95% CI, -0.37 to 0.54] for 3mg of macitentan vs placebo and 0.23 [-0.27 to 0.72] for 10 mg of macitentan vs placebo). Among 265 patients randomized in DUAL-2 (mean age 49.6 years; 81.9% women), 216 completed the study. In DUAL-2, the adjusted mean number of new digital ulcers was 1.44 in the 3-mg macitentan group (n = 88) and 1.46 in the 10-mg macitentan group (n = 88) compared with 1.21 in the placebo group (n = 89) (absolute difference, 0.23 [95% CI, -0.35 to 0.82] for 3 mg of macitentan vs placebo and 0.25 [95% CI, -0.34 to 0.84] for 10mg of macitenta