AB0285 EFFECTIVENESS OF IMMUNOSUPPRESSIVE THERAPY FOR CONNECTIVE TISSUE DISEASE–ASSOCIATED PULMONARY ARTERIAL HYPERTENSION
Authors: R. Kishikawa, M. Hatano, S. Ishii, M. Shimbo, A. Saito, S. Minatsuki, Y. Iwasaki, K. Fujio, I. Komuro
Journal: Annals of the Rheumatic Diseases (2021)

Background: Connective tissue disease (CTD) associated pulmonary arterial hypertension (PAH) is considered to be an indication for immunosuppressive therapy (IT) except scleroderma associated PAH. However, the response rate defined by improvement of WHO functional class and hemodynamic parameters is reported to be around 50% [1]. Since CTDs are systemic diseases, it may be difficult to evaluate the efficacy of IT by subjective symptoms. Although there are previous studies reporting that the combined use of IT and pulmonary vasodilators significantly improved hemodynamics [2], response to IT without titration of pulmonary vasodilators remains to be elucidated. Objectives: To examine whether IT is effective for CTD-PAH. Methods: We retrospectively examined the medical records of consecutive 13 patients with CTD-PAH (female 13, mean age 47 ± 15 years) treated with methylprednisolone (1 mg/kg/day, oral) and intravenous bolus cyclophosphamide (IVCY) (500 mg/m 2 ) every four weeks for six times. Patient characteristics are described in Table 1. Right heart catheterization (RHC) was done at prior to IT, before adding PAH specific agents, and at the fifth or sixth course of IVCY. In treated cases, the previous vasodilators remained unchanged during the first term of IT. Results: At the first follow up RHC, decrease of mean pulmonary arterial pressure over 5 mmHg was observed in all patients, and decrease of pulmonary vascular resistance (PVR) was observed in twelve out of 13 patients (Figure 1). Over 20% of PVR reduction was observed more in the patients of pulmonary vasodilator naïve and started IT within one year from symptoms than others (6/7 vs 1/6, p=0.03). Although six-minutes walk distance (6MWD) tended to be prolonged between first and second RHC (298 ± 70 m vs 382 ± 81 m; p=0.054; n = 9), 6MWD was shortened in some cases with good hemodynamic improvement (2/5). All patients were prescribed oral PAH specific agents finally, but no one needed parenteral prostanoids. Two patients (15%) died during maintenance therapy for causes other than PAH. Three-year and five-year survival rates were 91.7% and 81.5%, respectively. Conclusion: IT without titration of pulmonary vasodilators significantly improved hemodynamic parameters despite of less improvement in 6MWD in CTD-PAH patients. Considering that CTDs itself might affect the exercise tolerance regardless of PAH, these hemodynamic changes may contribute to better prognosis and IT might be considered especially for patients early in clinical courses and treatment naïve. References: [1]Jais X, Launay D, Yaici A, et al. Immunosupressive therapy in lupus-and mixed connective tissue disease-associated pulmonary arterial hypertension. ARTHRITIS RHEUM. 2008; 58(2): 521-531. [2]Yamamoto M S, Fukumoto Y, Sugimura K, et al. Intensive immunosuppressive therapy improves pulmonary hemodynamics and long-term prognosis in patients with pulmonary arterial hypertension associated with connective tissue diseasae. Circ J. 2011; 75: 2668-2674. Table 1. Characteristics of patients Patient Age, yr Connective Tissue Disease Years from symptom to immunosuppressive therapy Previous vasodilators vasodilators at final visit 1 47 SS 1.5 PGI2 ERA 2 62 SS, RA 2 none PDE5 3 32 SS 1 none ERA 4 57 SS, SSc 0.5 none PDE5 5 26 SS,MCTD, SLE,SSc 0.5 none PDE5 6 70 SSc, SS s/o 13 sGC, ERA sGC, ERA 7 32 SS s/o, SLE 0.1 none PDE5 8 31 MCTD 3 ERA,PDE5, PGI2 ERA,PDE5, PGI2 9 43 SSc, SLE 0.6 ERA, PDE5 ERA,PDE5, PGI2 10 67 MCTD,PM 0 none sGC 11 41 SS 0.1 none ERA, PDE5 12 69 SS 0.3 none PDE5 13 44 SS, MCTD s/o, SLE s/o 0.1 none ERA, sGC N.A, not acquired; s/o, suspect of; SS, Sjögren’s syndrome; RA, rheumatoid arthritis; SSc systemic sclerosis; SLE, systemic lupus erythematosus; MCTD, mixed connective tissue disease; PM, Polymyositis; PGI2, prostacyclin derivative; sGC, soluble guanylate cyclase stimulator; ERA, endothelin receptor antagonist; PDE5, phosphodiesterase type 5 inhibitor. Figure 1. Hemodynamic changes during immunosuppressive therapy Disclosure of Interests: Risa Kishikawa: None declared, Masaru Hatano Speakers bureau: Janssen Pharmaceutical K.K, Bayer Yakuhin, Ltd., Grant/research support from: Janssen Pharmaceutical K.K, Nippon Shinyaku Co., Ltd., MOCHIDA PHARMACEUTICAL CO., LTD., Satoshi Ishii: None declared, Mai Shimbo: None declared, Akihito Saito: None declared, Shun Minatsuki: None declared, Yukiko Iwasaki: None declared, Keishi Fujio Speakers bureau: Tanabe Mitsubishi, Bristol Myers, Eli Lilly, Chugai, Jansen, Pfizer, Ono, AbbVie, Ayumi, Astellas, Sanofi, Novartis, Daiichi Sankyo, Eisai, Asahi Kasei, Japan Blood Products Organization, and Kowa, Grant/research support from: Tanabe Mitsubishi, Bristol Myers, Eli Lilly, Chugai, AbbVie, Ayumi, Astellas, Sanofi, Eisai, Tsumura &amp; Co., and Asahi Kasei., Issei Komuro Speakers bureau: AstraZeneka, Daiichi Sankyo Company, Limited, Takeda Pharmaceutical Company Limited, Bayer Yakuhin, Ltd, Pfizer Japan Inc., and Ono Pharmaceutical Co., Ltd., Grant/research support from: Daiichi Sankyo Company, Ltd, Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Ltd, Mitsubishi Tanabe Pharma Corporation, Teijin Pharma Limited, Idorsia Pharmaceuticals Ltd, Otsuka Pharmaceutical Co., Ltd., Bayer Yakuhin, Ltd. Ono Pharmaceutical Co., Ltd. Toa Eiyo Ltd