PMID- 26016953
OWN - NLM
STAT- MEDLINE
DCOM- 20151116
LR  - 20181113
IS  - 2326-5205 (Electronic)
IS  - 2326-5191 (Print)
IS  - 2326-5191 (Linking)
VI  - 67
IP  - 9
DP  - 2015 Sep
TI  - Adverse Events in Connective Tissue Disease-Associated Pulmonary Arterial 
      Hypertension.
PG  - 2457-65
LID - 10.1002/art.39220 [doi]
AB  - 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.
CI  - (c) 2015, American College of Rheumatology.
FAU - Rhee, Rennie L
AU  - Rhee RL
AD  - University of Pennsylvania Perelman School of Medicine, Philadelphia.
FAU - Gabler, Nicole B
AU  - Gabler NB
AD  - University of Pennsylvania Perelman School of Medicine, Philadelphia.
FAU - Praestgaard, Amy
AU  - Praestgaard A
AD  - University of Pennsylvania Perelman School of Medicine, Philadelphia.
FAU - Merkel, Peter A
AU  - Merkel PA
AD  - University of Pennsylvania Perelman School of Medicine, Philadelphia.
FAU - Kawut, Steven M
AU  - Kawut SM
AD  - University of Pennsylvania Perelman School of Medicine, Philadelphia.
LA  - eng
GR  - K24 HL103844/HL/NHLBI NIH HHS/United States
GR  - T32 DK007785/DK/NIDDK NIH HHS/United States
GR  - K24-HL-103844/HL/NHLBI NIH HHS/United States
GR  - T32-DK-07785/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Arthritis Rheumatol
JT  - Arthritis & rheumatology (Hoboken, N.J.)
JID - 101623795
RN  - 0 (Antihypertensive Agents)
RN  - 0 (Endothelin Receptor Antagonists)
RN  - 0 (Phosphodiesterase 5 Inhibitors)
RN  - DCR9Z582X0 (Epoprostenol)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antihypertensive Agents/*adverse effects
MH  - Case-Control Studies
MH  - Clinical Trials, Phase III as Topic
MH  - Connective Tissue Diseases/*complications
MH  - *Drug-Related Side Effects and Adverse Reactions
MH  - Endothelin Receptor Antagonists/*adverse effects
MH  - Epoprostenol/*adverse effects/analogs & derivatives
MH  - Familial Primary Pulmonary Hypertension/drug therapy
MH  - Female
MH  - Humans
MH  - Hypertension, Pulmonary/*drug therapy/etiology
MH  - Male
MH  - Middle Aged
MH  - Phosphodiesterase 5 Inhibitors/*adverse effects
MH  - Randomized Controlled Trials as Topic
PMC - PMC4949955
MID - NIHMS801390
EDAT- 2015/05/29 06:00
MHDA- 2015/11/17 06:00
PMCR- 2016/07/19
CRDT- 2015/05/29 06:00
PHST- 2014/12/30 00:00 [received]
PHST- 2015/05/21 00:00 [accepted]
PHST- 2015/05/29 06:00 [entrez]
PHST- 2015/05/29 06:00 [pubmed]
PHST- 2015/11/17 06:00 [medline]
PHST- 2016/07/19 00:00 [pmc-release]
AID - 10.1002/art.39220 [doi]
PST - ppublish
SO  - Arthritis Rheumatol. 2015 Sep;67(9):2457-65. doi: 10.1002/art.39220.