Background/Purpose: Pulmonary arterial hypertension (PAH) is one of devastating organ involvements in patients with connective tissue diseases (CTDs). Recent introduction of molecular-targeting PAH drugs, such as prostanoids, endothelin receptor antagonists, and phosphodiesterase-5 inhibitors, has prolonged time to clinical worsening and survival in patients with PAH-CTD. On the other hand, several reports suggest potential efficacy of immunosuppressive treatment for PAH-CTD, but positioning of immunosuppressive treatment in the PAH treatment algorithm still remains uncertain. In this study, we determined baseline characteristics that predict short-term efficacy of immunosuppressive treatment in patients with PAH-CTD, using our single-center cohort, including those in the pre- and post-PAH drug era.  

Methods: This is a retrospective study involving 28 consecutive patients with PAH-CTD, consisting of 13 historical cases (diagnosis made between 1970 and 1990) and 15 recent cases (diagnosis made after 2000). These patients were selected from our PAH-CTD database, based on (i) diagnosis of PAH associated with systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD), or primary Sjögren syndrome (pSS), (ii) those who received corticosteroids (≥0.5 mg/kg/day prednisolone equivalent) with or without PAH drugs as an initial therapy, and (iii) observation period > 3 months. The short-term treatment response was regarded as improvement of WHO functional class (FC) at 3 months. Baseline clinical characteristics, including age at diagnosis of PAH and underlying CTD, WHO-FC, hemodynamic parameters, and immunologic and autoantibody profiles, and initial treatment regimen were obtained from prospectively collected database.

Results: PAH-CTD patients treated initially with immunosuppressive treatment consisted of 11 with SLE, 14 with MCTD, and 3 with pSS. Of these, 15 (54%), including 6 historical and 9 recent cases, were short-term responders. Simultaneous diagnosis of PAH and underlying CTD was more frequent in responders than in non-responders (80% versus 15%, P = 0.002), but there was no difference in distribution underlying CTD, WHO-FC, hemodynamic parameters, or immunologic and autoantibody profiles between responders and non-responders. In terms of the initial treatment regimen, use of cyclophosphamide (CY) was associated with a therapeutic response, while corticosteroids without any immunosuppressant was associated with no response (P = 0.003 and 0.0002, respectively). Interestingly, use of any PAH drugs was not associated with the short-term response.

Conclusion: Patients with SLE, MCTD, and pSS who were diagnosed as having underlying CTD and PAH simultaneously are likely to achieve a short-term response to immunosuppressive treatment. These patients should be treated with an intensive immunosuppressive regimen containing cyclophosphamide.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/baseline-characteristics-that-predict-a-short-term-response-to-immunosuppressive-treatment-in-patients-with-pulmonary-arterial-hypertension-associated-with-connective-tissue-disease/