Effect of Macitentan on the Development of New Ischemic Digital Ulcers in Patients With Systemic Sclerosis
| Autor: | Khanna, D, Denton, Cp, Merkel, Pa, Krieg, T, Le Brun FO, Marr, A, Papadakis, K, Pope, J, Matucci Cerinic, M, Furst, De, Zochling, J, Stevens, W, Proudman, S, Feenstra, J, Youssef, P, Soroka, N, Tyabut, T, Mikhailova, Ei, Rashkov, R, Batalov, A, Yablanski, K, Keystone, E, Jones, N, Dunne, J, Masetto, A, Calabresse, Rj, Cabezas, Pc, Silva, Mo, Sariego, Ia, Escalente, Wj, Anić, B, Kaliterna, Dm, Morović Vergles, J, Novak, S, Prus, V, Artuković, M, Soukup, T, Bečvař, R, Fojtík, Z, Mouthon, L, Kollert, F, Krieg, Tm, Riemekasten, G, Lahner, N, Fierlbeck, G, Ahmadi Simab, K, Diehm, C, Szücs, G, Kumánovics, G, Nagy, G, Pal, S, Veeravalli, Sc, Danda, D, Ferri, Clodoveo, Cerinic, Mm, Cozzi, F, Ferraccioli, G, Wiland, P, Rudnicak, L, Zwolak, R, Roszkiewicz, J, Oleynikov, V, Nikulenkova, N, Lesnyak, O, Kaydashev, I, Kurytar, O, Piura, O, Chopyak, V, Chatterjee, S, Hsu, V, Hummers, L, Martin, R, Domsic, R, Schiopu, E, Shanahan, J, Murphy, Ft, Kaine, J, Davis, W, Grau, R, Eimon, A, Catoggio, Lj, Laborde, Ha, Caeiro, F, Savio, Vg, Amitrano, Cb, Vanthuyne, M, Zeng, X, Zhang, X, Zhu, P, Velásquez Franco CJ, Choueka, Ps, Sanchez, Pj, Hermann, W, Sticherling, M, Steinbrink, K, Hein, R, Aschoff, R, Sfikakis, P, Settas, L, Fraser, A, Veale, D, Balbir Gurman, A, Lidar, M, Litinsky, I, Levy, Y, Carrillo Vazquez SM, Rodriguez Reyna, T, Medrano Ramirez, G, Morales Torres, J, Pacheco Tena CF, Sanchez Ortiz, A, Vonk, Mc, Stebbings, S, Solanki, K, Steele, R, Ng, Kp, Zubrzycka Sienkiewicz, A, Brzosko, M, Szepietowski, Jc, Hrycaj, P, da Silva IF, dos Santos Lda, C, Coelho, Pj, Rios, G, Chernykh, T, Grunina, E, Stanislav, M, Ally, M, Kalla, A, Birlik, Am, Kovalenko, V, Petrov, A, Shevchuk, S, Stanislavchuk, M, Anderson, M, Herrick, A, Belch, J, Chung, L, Csuka, Me, Frech, T, Goldberg, A, Kahaleh, B, Mayes, Md, Rothfield, N, Simms, Rw, Spiera, R, Steen, V, Varga, J, Sikes, D, Derk, Ct, Kohen, M. D. |
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| Přispěvatelé: | UCL - (SLuc) Service de rhumatologie |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male Settore MED/16 - REUMATOLOGIA systemic sclerosis Peripheral edema Administration Oral law.invention Scleroderma chemistry.chemical_compound 0302 clinical medicine Randomized controlled trial law BIOMEDICINA I ZDRAVSTVO. Kliničke medicinske znanosti. Interna medicina Sulfonamides Endothelin-1 Medicine (all) General Medicine Middle Aged Administration Female medicine.symptom BIOMEDICINA I ZDRAVSTVO. Temeljne medicinske znanosti Oral medicine.medical_specialty Double-Blind Method Fingers Humans Outcome Assessment (Health Care) Pyrimidines Scleroderma Systemic Skin Ulcer Anemia Macitentan Digital Ulcers Systemic Sclerosis Placebo 03 medical and health sciences Internal medicine medicine Adverse effect BIOMEDICINE AND HEALTHCARE. Clinical Medical Sciences. Internal Medicine Macitentan 030203 arthritis & rheumatology business.industry BIOMEDICINE AND HEALTHCARE. Basic Medical Sciences Systemic Skin ulcer medicine.disease Surgery Clinical trial 030104 developmental biology chemistry Inflammatory diseases Radboud Institute for Health Sciences [Radboudumc 5] business |
| Zdroj: | JAMA Volume 315 Issue 18 JAMA : the journal of the American Medical Association, Vol. 315, no.18, p. 1975-1988 (2016) Jama : Journal of the American Medical Association, 315, 1975-88 Jama : Journal of the American Medical Association, 315, 18, pp. 1975-88 |
| ISSN: | 0098-7484 |
| Popis: | Contains fulltext : 172407.pdf (Publisher’s version ) (Closed access) 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). MAIN OUTCOMES AND MEASURES: The primary outcome for each trial was 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 3 mg 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 10 mg of macitentan vs placebo). Adverse events more frequently associated with macitentan than with placebo were headache, peripheral edema, skin ulcer, anemia, upper respiratory tract infection, diarrhea, and nasopharyngitis. CONCLUSIONS AND RELEVANCE: Among patients with systemic sclerosis and active ischemic digital ulcers, treatment with macitentan did not reduce new digital ulcers over 16 weeks. These results do not support the use of macitentan for the treatment of digital ulcers in this patient population. TRIAL REGISTRATION: clinicaltrials.gov Identifiers: NCT01474109, NCT01474122. |
| Databáze: | OpenAIRE |
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