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 firstline 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.Conclusion. 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.

ASPIRE registry: Assessing the Spectrum of Pulmonary hypertension Identified at a REferral centre

“…The proportion of patients with IPAH with a positive vasodilator response (6%) was of a similar order to that in previous registries [29,30]. As observed elsewhere, survival in PAH-SSc was inferior to that of IPAH [18,34,35] and the number of cases of PAH-CTD associated with CTDs other than SSc was small [18,[36][37][38][39][40][41]. In contrast to the French registry, limited cutaneous SSc was far more common than the diffuse form (94% versus 67% of PAH-CTD-SSc) [29].…”

Exercise‐induced pulmonary hypertension associated with systemic sclerosis: Four distinct entities

“…The prevalence of resting PAH in CTD is ϳ2.3-10 cases per million (5), typically mostly SSc patients (5-50%) (6)(7)(8)(9)(10)(11)(12), patients with mixed CTD (21-29%) (13), and patients with systemic lupus erythematosus (5-43%) (14)(15)(16). Based on right heart catheterization, the prevalence of resting PAH in SSc is likely 7.9-20% (7,17).…”

Guidelines for the diagnosis and treatment of pulmonary hypertension

“…Immunosuppressive therapy combining glucocorticosteroids and cyclophosphamide may result in clinical improvement in patients with PAH associated with systemic lupus erythematosus or mixed CTD [201].…”