Long-Term Prognostic and Hemodynamic Outcomes of Intensive Immunosuppressive Therapy in Patients With Pulmonary Arterial Hypertension Associated With Connective Tissue Disease

Int J Rheum Dis. 2025 Oct;28(10):e70431. doi: 10.1111/1756-185X.70431.

Abstract

Background: Intensive immunosuppressive therapy (IIT) is recommended for PAH associated with connective tissue disease (CTD-PAH). However, the long-term effects of IIT on pulmonary hemodynamics in this population remain unexplored. Additionally, its effectiveness in patients with systemic sclerosis (SSc)-associated PAH (SSc-PAH) is poorly understood.

Methods and results: This retrospective analysis included 69 consecutive patients with CTD-PAH treated at our institution (men/women: 9/60, mean age 55.3 ± 14.0 years). Patients were divided into two groups, wherein 41 patients received IIT (IIT group) and 28 did not (non-IIT group). Both groups received conventional vasodilator therapy. The prognosis and pulmonary hemodynamics were evaluated in all patients. The IIT group exhibited significantly lower rates of PAH-related mortality (p < 0.001) compared with the non-IIT group. The mean PAP (mPAP) improved significantly in the IIT group during the follow-up (baseline: 38.7 ± 12.2 mmHg; 1 year: 27.0 ± 8.2 mmHg; 5 years: 26.8 ± 7.3 mmHg, p < 0.05), while it remained unchanged in the non-IIT group. None of the patients with CTD-PAH required IIT retreatment. Among the 27 patients with SSc-PAH, the IIT group (n = 9) showed a significantly greater improvement in mPAP compared with the non-IIT group (n = 18) (ΔmPAP at 1 year: -13.4 ± 6.5 mmHg in IIT group vs. -3.0 ± 6.2 mmHg in non-IIT group, p < 0.001).

Conclusions: This study's findings suggest that IIT may lead to sustained improvements in pulmonary hemodynamics and better long-term outcomes in patients with CTD-PAH, including potential benefits in those with SSc-PAH.

Keywords: PAH associated with connective tissue disease; intensive immunosuppressive therapy; systemic sclerosis.

MeSH terms

  • Adult
  • Aged
  • Antihypertensive Agents / therapeutic use
  • Arterial Pressure* / drug effects
  • Connective Tissue Diseases* / complications
  • Connective Tissue Diseases* / diagnosis
  • Connective Tissue Diseases* / drug therapy
  • Connective Tissue Diseases* / mortality
  • Connective Tissue Diseases* / physiopathology
  • Female
  • Hemodynamics* / drug effects
  • Humans
  • Hypertension, Pulmonary* / diagnosis
  • Hypertension, Pulmonary* / drug therapy
  • Hypertension, Pulmonary* / etiology
  • Hypertension, Pulmonary* / mortality
  • Hypertension, Pulmonary* / physiopathology
  • Immunosuppressive Agents* / administration & dosage
  • Immunosuppressive Agents* / adverse effects
  • Immunosuppressive Agents* / therapeutic use
  • Male
  • Middle Aged
  • Pulmonary Arterial Hypertension* / diagnosis
  • Pulmonary Arterial Hypertension* / drug therapy
  • Pulmonary Arterial Hypertension* / etiology
  • Pulmonary Arterial Hypertension* / mortality
  • Pulmonary Arterial Hypertension* / physiopathology
  • Pulmonary Artery* / drug effects
  • Pulmonary Artery* / physiopathology
  • Retrospective Studies
  • Scleroderma, Systemic* / complications
  • Scleroderma, Systemic* / diagnosis
  • Scleroderma, Systemic* / drug therapy
  • Scleroderma, Systemic* / mortality
  • Time Factors
  • Treatment Outcome

Substances

  • Immunosuppressive Agents
  • Antihypertensive Agents