title: Tadalafil in idiopathic or heritable pulmonary arterial hypertension (PAH) compared to PAH associated with connective tissue disease.
abstract: BACKGROUND
  The primary objective of this post hoc analysis was to evaluate clinical outcomes of tadalafil in patients with pulmonary arterial hypertension (PAH) associated with connective tissue disease (CTD-PAH) compared with patients with idiopathic/heritable PAH (I/H-PAH) for primary and key secondary efficacy endpoints, and safety. This analysis included adult patients with CTD-PAH or I/H-PAH who participated in the PHIRST and PHIRST-2 studies.
  
  
  METHODS
  Patients were randomized 1:1:1:1:1 to tadalafil (2.5, 10, 20, or 40mg) or placebo in the PHIRST study and the majority of these patients were subsequently assigned 40mg in PHIRST-2. Patients taking 20mg in PHIRST without demonstrating clinical worsening continued on 20mg in PHIRST-2. Outcomes analyzed included 6MWD, WHO-FC, and incidence and time to first occurrence of clinical worsening. Safety was assessed through evaluation of adverse events (AEs), clinical laboratory data, electrocardiograms, and physical examinations.
  
  
  RESULTS
  Increased 6MWD in PHIRST was maintained in both CTD-PAH and I/H-PAH subgroups for 52weeks. Patients with CTD-PAH tended to be older, were more likely female, had lower exercise capacity, were more likely to have clinical worsening, and experienced AEs more frequently than patients with I/H-PAH.
  
  
  CONCLUSIONS
  The effect of tadalafil treatment in patients enrolled in both PHIRST studies was detectable for both I/H-PAH and CTD-PAH subgroups. In general, subgroup differences were modest. Patients with CTD-PAH may perform less well than patients with I/H-PAH in safety and efficacy measures in all treatment groups, which is similar to other studies demonstrating a worse prognosis for patients with CTD-PAH.
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy. Electronic address: nazzareno.galie@unibo.it.
authors.forename: Nazzareno
authors.initials: N
authors.lastname: Galiè
authors.affiliation: Centre for Rheumatology at the Royal Free, and University College Medical School, Hampstead, London, United Kingdom.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Denton
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Dardi
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Manes
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy.
authors.forename: Gaia
authors.initials: G
authors.lastname: Mazzanti
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Baohui
authors.initials: B
authors.lastname: Li
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Lucio
authors.initials: L
authors.lastname: Varanese
authors.affiliation: inVentiv Clinical Solutions, LLC, Indianapolis, IN, USA.
authors.forename: Anne
authors.initials: A
authors.lastname: Esler
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Cathi
authors.initials: C
authors.lastname: Harmon
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Palazzini
mesh_terms: D003240:Connective Tissue Diseases / Q000150:complications*; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring / Q000379:methods; D064420:Drug-Related Side Effects and Adverse Reactions / Q000175:diagnosis*; D004562:Electrocardiography / Q000379:methods; D065627:Familial Primary Pulmonary Hypertension / Q000175:diagnosis / Q000188:drug therapy; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology; D008297:Male; D008875:Middle Aged; D010808:Physical Examination / Q000379:methods; D000068581:Tadalafil / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D014665:Vasodilator Agents; D000068581:Tadalafil
keywords: Associated PAH; Heritable; Idiopathic; PHIRST; PHIRST-2