OBJECTIVE:Patients with connective tissue disease (CTD)-associated pulmonary arterial hypertension (PAH) have a poorer prognosis compared to those with idiopathic PAH, but little is known about the differences in treatment-related adverse events (AEs) and serious adverse events (SAEs) between these groups. This study was undertaken to characterize these differences. METHODS: Individual patient-level data from 10 randomized controlled trials of therapies for PAH were obtained from the US Food and Drug Administration. Patients diagnosed as having either CTD-associated PAH or idiopathic PAH were included. A treatment-by-diagnosis interaction term was used to examine whether the effect of treatment on occurrence of AEs differed between patients with CTD-associated PAH and those with idiopathic PAH. Studies were pooled using fixed-effect models. RESULTS: The study sample included 2,370 participants: 716 with CTD-associated PAH and 1,654 with idiopathic PAH. In the active treatment group compared to the placebo group, the risk of AEs was higher among patients with CTD-associated PAH than among those with idiopathic PAH (odds ratio [OR] 1.57, 95% confidence interval [95% CI] 1.00-2.47 versus OR 0.94, 95% CI 0.69-1.26; P for interaction = 0.061), but there was no difference in the risk of SAEs in analyses adjusted for age, race, sex, hemodynamic findings, and laboratory values. Despite the higher occurrence of AEs in patients with CTD-associated PAH assigned to active therapy compared to those receiving placebo, the risk of drug discontinuation due to an AE was similar to that in patients with idiopathic PAH assigned to active therapy (P for interaction = 0.27). CONCLUSION: Patients with CTD-associated PAH experienced more treatment-related AEs compared to those with idiopathic PAH in therapeutic clinical trials. These findings suggest that the overall benefit of advanced therapies for PAH may be attenuated by the greater frequency of AEs.
RCT Entities:
OBJECTIVE:Patients with connective tissue disease (CTD)-associated pulmonary arterial hypertension (PAH) have a poorer prognosis compared to those with idiopathic PAH, but little is known about the differences in treatment-related adverse events (AEs) and serious adverse events (SAEs) between these groups. This study was undertaken to characterize these differences. METHODS: Individual patient-level data from 10 randomized controlled trials of therapies for PAH were obtained from the US Food and Drug Administration. Patients diagnosed as having either CTD-associated PAH or idiopathic PAH were included. A treatment-by-diagnosis interaction term was used to examine whether the effect of treatment on occurrence of AEs differed between patients with CTD-associated PAH and those with idiopathic PAH. Studies were pooled using fixed-effect models. RESULTS: The study sample included 2,370 participants: 716 with CTD-associated PAH and 1,654 with idiopathic PAH. In the active treatment group compared to the placebo group, the risk of AEs was higher among patients with CTD-associated PAH than among those with idiopathic PAH (odds ratio [OR] 1.57, 95% confidence interval [95% CI] 1.00-2.47 versus OR 0.94, 95% CI 0.69-1.26; P for interaction = 0.061), but there was no difference in the risk of SAEs in analyses adjusted for age, race, sex, hemodynamic findings, and laboratory values. Despite the higher occurrence of AEs in patients with CTD-associated PAH assigned to active therapy compared to those receiving placebo, the risk of drug discontinuation due to an AE was similar to that in patients with idiopathic PAH assigned to active therapy (P for interaction = 0.27). CONCLUSION:Patients with CTD-associated PAH experienced more treatment-related AEs compared to those with idiopathic PAH in therapeutic clinical trials. These findings suggest that the overall benefit of advanced therapies for PAH may be attenuated by the greater frequency of AEs.
Authors: Micah R Fisher; Stephen C Mathai; Hunter C Champion; Reda E Girgis; Traci Housten-Harris; Laura Hummers; Jerry A Krishnan; Fredrick Wigley; Paul M Hassoun Journal: Arthritis Rheum Date: 2006-09
Authors: Robyn J Barst; David Langleben; David Badesch; Adaani Frost; E Clinton Lawrence; Shelley Shapiro; Robert Naeije; Nazzareno Galie Journal: J Am Coll Cardiol Date: 2006-04-24 Impact factor: 24.094
Authors: Nazzareno Galiè; Hossein A Ghofrani; Adam Torbicki; Robyn J Barst; Lewis J Rubin; David Badesch; Thomas Fleming; Tamiza Parpia; Gary Burgess; Angelo Branzi; Friedrich Grimminger; Marcin Kurzyna; Gérald Simonneau Journal: N Engl J Med Date: 2005-11-17 Impact factor: 91.245
Authors: Vallerie V McLaughlin; Raymond L Benza; Lewis J Rubin; Richard N Channick; Robert Voswinckel; Victor F Tapson; Ivan M Robbins; Horst Olschewski; Melvyn Rubenfire; Werner Seeger Journal: J Am Coll Cardiol Date: 2010-05-04 Impact factor: 24.094
Authors: Lionel Schachna; Fredrick M Wigley; Betty Chang; Barbara White; Robert A Wise; Allan C Gelber Journal: Chest Date: 2003-12 Impact factor: 9.410
Authors: D Mukerjee; D St George; B Coleiro; C Knight; C P Denton; J Davar; C M Black; J G Coghlan Journal: Ann Rheum Dis Date: 2003-11 Impact factor: 19.103
Authors: John H Newman; Stuart Rich; Steven H Abman; John H Alexander; John Barnard; Gerald J Beck; Raymond L Benza; Todd M Bull; Stephen Y Chan; Hyung J Chun; Declan Doogan; Jocelyn Dupuis; Serpil C Erzurum; Robert P Frantz; Mark Geraci; Hunter Gillies; Mark Gladwin; Michael P Gray; Anna R Hemnes; Roy S Herbst; Adrian F Hernandez; Nicholas S Hill; Evelyn M Horn; Kendall Hunter; Zhi-Cheng Jing; Roger Johns; Sanjay Kaul; Steven M Kawut; Tim Lahm; Jane A Leopold; Greg D Lewis; Stephen C Mathai; Vallerie V McLaughlin; Evangelos D Michelakis; Steven D Nathan; William Nichols; Grier Page; Marlene Rabinovitch; Jonathan Rich; Franz Rischard; Sharon Rounds; Sanjiv J Shah; Victor F Tapson; Naomi Lowy; Norman Stockbridge; Gail Weinmann; Lei Xiao Journal: Am J Respir Crit Care Med Date: 2017-06-15 Impact factor: 21.405
Authors: Sean Gaine; Kelly Chin; Gerry Coghlan; Richard Channick; Lilla Di Scala; Nazzareno Galiè; Hossein-Ardeschir Ghofrani; Irene M Lang; Vallerie McLaughlin; Ralph Preiss; Lewis J Rubin; Gérald Simonneau; Olivier Sitbon; Victor F Tapson; Marius M Hoeper Journal: Eur Respir J Date: 2017-08-17 Impact factor: 16.671
Authors: Rafael González-Tajuelo; María de la Fuente-Fernández; Daniel Morales-Cano; Antonio Muñoz-Callejas; Elena González-Sánchez; Javier Silván; Juan Manuel Serrador; Susana Cadenas; Bianca Barreira; Marina Espartero-Santos; Carlos Gamallo; Esther F Vicente-Rabaneda; Santos Castañeda; Francisco Pérez-Vizcaíno; Ángel Cogolludo; Luis Jesús Jiménez-Borreguero; Ana Urzainqui Journal: Arthritis Rheumatol Date: 2020-01-28 Impact factor: 10.995