title: Immunosuppressive therapy in lupus- and mixed connective tissue disease-associated pulmonary arterial hypertension: a retrospective analysis of twenty-three cases.
abstract: OBJECTIVE
  To describe the response to first-line immunosuppressive therapy with or without pulmonary vasodilators in pulmonary arterial hypertension (PAH) associated with systemic lupus erythematosus (SLE) or mixed connective tissue disease (MCTD).
  
  
  METHODS
  Twenty-three consecutive patients with SLE- or MCTD-associated PAH treated with first-line immunosuppressive therapy either alone (n = 16) or in combination with pulmonary vasodilators (n = 7) were evaluated according to clinical and hemodynamic criteria before and after immunosuppressive therapy. Responders were defined as patients in New York Heart Association (NYHA) functional class I or II with hemodynamic improvement after the last pulse of cyclophosphamide.
  
  
  RESULTS
  Among the 16 patients treated with first-line immunosuppressive therapy alone, 8 (50%) were responders. These patients had a significantly improved NYHA functional class, 6-minute walking distance, and mean pulmonary artery pressure. Patients in NYHA functional class I or II and/or a cardiac index >3.1 liters/minute/m(2) at baseline were more likely to benefit from immunosuppressive therapy. Six of the 8 nonresponders subsequently improved with pulmonary vasodilators. Among the 7 patients who were initially treated with immunosuppressive therapy and pulmonary vasodilators, 4 (57.1%) were responders.
  
  
  CONCLUSIONS
  PAH associated with SLE or MCTD may respond to a treatment combining cyclophosphamide and glucocorticoids. Patients who could benefit from this immunosuppressive therapy could be those who have less severe disease at baseline. For patients with more severe disease, pulmonary vasodilators should be started, possibly in combination with immunosuppressants. In any case, clinical and hemodynamic evaluations are mandatory to monitor the response and adapt the treatment. These retrospective and uncontrolled data need to be confirmed by randomized controlled trials.
authors.affiliation: Hôpital Antoine-Béclère, Assistance Publique Hôpitaux de Paris, Université Paris-Sud, Clamart, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Jais
authors.forename: David
authors.initials: D
authors.lastname: Launay
authors.forename: Azzedine
authors.initials: A
authors.lastname: Yaici
authors.forename: Jérôme
authors.initials: J
authors.lastname: Le Pavec
authors.forename: Colas
authors.initials: C
authors.lastname: Tchérakian
authors.forename: Olivier
authors.initials: O
authors.lastname: Sitbon
authors.forename: Gérald
authors.initials: G
authors.lastname: Simonneau
authors.forename: Marc
authors.initials: M
authors.lastname: Humbert
mesh_terms: D000328:Adult; D000465:Algorithms; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000009:adverse effects; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D008180:Lupus Erythematosus, Systemic / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D008947:Mixed Connective Tissue Disease / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D011237:Predictive Value of Tests; D020551:Pulse Therapy, Drug; D012189:Retrospective Studies; D015996:Survival Rate; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000627:therapeutic use
chemical_list: D007166:Immunosuppressive Agents; D014665:Vasodilator Agents; D003520:Cyclophosphamide