Immunosuppressive therapy in patients with connective tissue disease-associated pulmonary arterial hypertension: A systematic review

Int J Rheum Dis. 2022 Sep;25(9):982-990. doi: 10.1111/1756-185X.14368. Epub 2022 Jun 14.

Abstract

Objectives: It is currently accepted that inflammation plays an important role in the pathogenesis of connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH). However, the efficacy of immunosuppressive therapy remains anecdotal. The objective of this systematic review was to evaluate the efficacy of immunosuppressive therapy in patients with CTD-PAH and to further assess whether response differs between CTD subtypes and clinical features.

Methods: We systematically searched studies reporting the treatment response of immunosuppressants and biological agents in CTD-PAH from PUBMED, EMBASE, the Cochrane Library, and Scopus. Studies had to report treatment regime and response criteria. The risk of bias was assessed using the Newcastle-Ottawa scale.

Results: Seven independent cohorts, 1 trial, and 1 case-series encompassing 439 patients with CTD-PAH were included. Patients were divided into 2 groups according to the therapeutic regimen. There were 146 patients in the immunosuppressants group with better heart function at baseline and 52.1% (76/146) of them were responders. There were 236 patients treated with immunosuppressants combined with PAH-specific therapy who showed more severity at baseline and 41.1% (97/236) of them were responders. Among different CTD subtypes, patients with systemic lupus erythematosus-associated PAH (SLE-PAH) showed a better response to immunosuppressants (response rate 48.1%). What is more, 1 randomized controlled trial showed the potential therapeutic value of rituximab (n = 57) in CTD-PAH patients.

Conclusions: Current studies support the use of immunosuppressive therapy in CTD-PAH, especially in SLE-PAH. Further studies on biological agents and the therapeutic effect of different immunosuppressants are still needed.

Keywords: biological agent; connective tissue disease; immunosuppressive therapy; pulmonary arterial hypertension.

Publication types

  • Systematic Review

MeSH terms

  • Biological Factors / therapeutic use
  • Connective Tissue Diseases* / complications
  • Connective Tissue Diseases* / diagnosis
  • Connective Tissue Diseases* / drug therapy
  • Humans
  • Hypertension, Pulmonary* / diagnosis
  • Hypertension, Pulmonary* / drug therapy
  • Hypertension, Pulmonary* / etiology
  • Immunosuppression Therapy
  • Immunosuppressive Agents / adverse effects
  • Lupus Erythematosus, Systemic* / complications
  • Lupus Erythematosus, Systemic* / diagnosis
  • Lupus Erythematosus, Systemic* / drug therapy
  • Pulmonary Arterial Hypertension* / diagnosis
  • Pulmonary Arterial Hypertension* / drug therapy
  • Pulmonary Arterial Hypertension* / etiology

Substances

  • Biological Factors
  • Immunosuppressive Agents