Selexipag for the treatment of connective tissue disease-associated pulmonary arterial hypertension

Eur Respir J. 2017 Aug 17;50(2):1602493. doi: 10.1183/13993003.02493-2016. Print 2017 Aug.


Patients with connective tissue disease-associated pulmonary arterial hypertension (PAH-CTD) have a poor prognosis compared with other aetiologies. The underlying CTD can influence treatment response and outcomes. We characterised the GRIPHON study PAH-CTD subgroup and evaluated response to selexipag.Of 334 patients with PAH-CTD, PAH was associated with systemic sclerosis (PAH-SSc) in 170, systemic lupus erythematosus (PAH-SLE) in 82 and mixed CTD/CTD-other in 82. For the primary composite endpoint of morbidity/mortality, hazard ratios (HR) and 95% CI were calculated using Cox proportional hazard models.Compared with the overall GRIPHON population, the CTD subgroup was slightly older with a greater proportion of females and shorter time since diagnosis. Patients with PAH-SSc appeared to be more impaired at baseline, with a more progressive disease course. The converse was observed for PAH-SLE. Selexipag reduced the risk of composite morbidity/mortality events in patients with PAH-CTD by 41% (HR 0.59; 95% CI 0.41-0.85). Treatment effect was consistent irrespective of baseline PAH therapy or CTD subtype (interaction p=0.87 and 0.89, respectively). Adverse events were predominately prostacyclin-related and known for selexipag treatment.GRIPHON has allowed the comprehensive characterisation of patients with PAH-CTD. Selexipag delayed progression of PAH and was well-tolerated among PAH-CTD patients, including those with PAH-SSc and PAH-SLE.

Trial registration: NCT01106014.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Acetamides* / administration & dosage
  • Acetamides* / adverse effects
  • Adult
  • Antihypertensive Agents / administration & dosage
  • Antihypertensive Agents / adverse effects
  • Disease Progression
  • Double-Blind Method
  • Female
  • Humans
  • Hypertension, Pulmonary* / diagnosis
  • Hypertension, Pulmonary* / drug therapy
  • Hypertension, Pulmonary* / etiology
  • Hypertension, Pulmonary* / mortality
  • Lupus Erythematosus, Systemic / complications*
  • Male
  • Middle Aged
  • Outcome Assessment, Health Care
  • Pyrazines* / administration & dosage
  • Pyrazines* / adverse effects
  • Risk Assessment
  • Scleroderma, Systemic / complications*
  • Survival Analysis


  • Acetamides
  • Antihypertensive Agents
  • Pyrazines
  • selexipag

Associated data