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

• Published in: The European respiratory journal Vol. 50; no. 2; p. 1602493
• Main Authors: Gaine, Sean, Chin, Kelly, Coghlan, Gerry, Channick, Richard, Di Scala, Lilla, Galiè, Nazzareno, Ghofrani, Hossein-Ardeschir, Lang, Irene M., McLaughlin, Vallerie, Preiss, Ralph, Rubin, Lewis J., Simonneau, Gérald, Sitbon, Olivier, Tapson, Victor F., Hoeper, Marius M.
• Format: Journal Article
• Language: English
• Published: England European Respiratory Society Journals Ltd 01.08.2017; European Respiratory Society
• Subjects: Acetamides - administration & dosage; Acetamides - adverse effects; Adult; Antihypertensive Agents - administration & dosage; Antihypertensive Agents - adverse effects; Disease Progression; Double-Blind Method; Female; Humans; Hypertension; Hypertension, Pulmonary - diagnosis; Hypertension, Pulmonary - drug therapy; Hypertension, Pulmonary - etiology; Hypertension, Pulmonary - mortality; Lung diseases; Lupus Erythematosus, Systemic - complications; Male; Middle Aged; Morbidity; Mortality; Original; Outcome Assessment (Health Care); Prostacyclin; Pulmonary hypertension; Pyrazines - administration & dosage; Pyrazines - adverse effects; Risk Assessment; Scleroderma, Systemic - complications; Survival Analysis; Systemic lupus erythematosus; Systemic sclerosis
• ISSN: 0903-1936; 1399-3003; 1399-3003
• DOI: 10.1183/13993003.02493-2016

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.