title: Immunosuppressive therapy in connective tissue diseases-associated pulmonary arterial hypertension.
abstract: OBJECTIVE
  Immune and inflammatory mechanisms could play a significant role in pulmonary arterial hypertension (PAH) genesis or progression, especially in patients with connective tissue diseases. Immunosuppressive therapy should be better evaluated in this setting.
  
  
  METHODS
  Monocentric retrospective study.
  
  
  METHODS
  We reviewed the clinical and hemodynamic effects of immunosuppressants administered as first-line monotherapy to 28 consecutive patients with connective tissue disease-associated PAH.
  
  
  METHODS
  All patients received a monthly IV bolus of cyclophosphamide, 600 mg/m2, for at least 3 months, and 22 of 28 patients received systemic glucocorticosteroids. Responders to immunosuppressive therapy were defined as patients who remained in New York Heart Association (NYHA) functional class I or II with sustained hemodynamic improvement after at least 1 year of immunosuppressive therapy without addition of prostanoids, phosphodiesterase type 5 inhibitors, or endothelin receptor antagonists.
  
  
  RESULTS
  Eight of 28 patients (systemic lupus erythematosus [SLE], n = 5; mixed connective tissue disease [MCTD], n = 3) [29%] were responders. These patients had a significantly improved 6-min walking distance (available in five patients) and a significant improvement in hemodynamic function. No patients with systemic sclerosis responded, while 5 of 12 patients with SLE and 3 of 8 patients with MCTD did respond. Survival analysis indicated that responders had a better survival than nonresponders. Patients with a lower baseline NYHA functional class and better baseline pulmonary hemodynamics (p < 0.05) were more likely to benefit from immunosuppressive therapy.
  
  
  CONCLUSIONS
  PAH associated with SLE or MCTD might respond to a treatment combining glucocorticosteroids and cyclophosphamide.
authors.affiliation: Centre National de Référence de l'Hypertension Artérielle Pulmonaire, UPRES EA2705, Service de Pneumologie et Réanimation Respiratoire, Hôpital Antoine Béclère, Assistance Publique Hôpitaux de Paris, Université Paris-Sud, Clamart, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Sanchez
authors.forename: Olivier
authors.initials: O
authors.lastname: Sitbon
authors.forename: Xavier
authors.initials: X
authors.lastname: Jaïs
authors.forename: Gérald
authors.initials: G
authors.lastname: Simonneau
authors.forename: Marc
authors.initials: M
authors.lastname: Humbert
mesh_terms: D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D003240:Connective Tissue Diseases / Q000145:classification / Q000150:complications / Q000188:drug therapy*; D003520:Cyclophosphamide / Q000627:therapeutic use*; D005080:Exercise Test / Q000379:methods; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy / Q000209:etiology* / Q000503:physiopathology; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012720:Severity of Illness Index
chemical_list: D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide