AbstractObjectivesIt 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.MethodsWe 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.ResultsSeven 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.ConclusionsCurrent 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.