Comparison of Baseline Clinical Characteristics between Asian Vs. Non-Asian Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) from International PNH Registry

Background: PNH is clinically characterized by intravascular haemolysis, bone marrow failure and thrombosis. Thrombosis and bleeding/serious infections have been reported as major causes of death in PNH. The difference in clinical manifestations of PNH among different races has also been suggested; however, it has not been clearly demonstrated due to rarity of the disease. Objectives: The aim of this study was to clarify whether the racial background of patients with PNH affects their clinical characteristics. Methods: As of June 5, 2017, 4,928 patients were enrolled in the International PNH Registry. After excluding patients with missing data for race, birth date, sex, enrollment date, and/or treatment status with eculizumab, 1,793 patients, who were eculizumab naïve at enrollment and had ≥1% GPI-deficient granulocytes or erythrocytes, were selected for analysis. The study population was divided into two cohorts according to their racial background. The "Asian cohort" consisted of patients with Asian or mixed Asian race (N=246), and the non-Asian cohort consisted of patients with White/Caucasian, Black/African descent and other racial background (N=1547). "Asian cohort" was further divided into "Asians in Asia cohort" (N=202) where the patients were enrolled in the registry from Japan (N=22), South Korea (N=122), Taiwan (N=25), and other Asian countries (N=33), and "Asians in non-Asia cohort" where Asian patients were enrolled from countries outside Asia (N=44). Baseline was defined as enrollment in the registry for all patients. Results: Median (Q1, Q3) disease duration (time from disease start to enrollment) was 1.6 years (0.3, 6.1) for Asian cohort and 1.2 years (0.4, 5.0) for non-Asian cohort. There was no significant difference in sex ratio, median age, and the proportion of patients with a history of bone marrow disorder, aplastic anemia, or myelodysplastic syndrome between the two cohorts. The mean platelet counts at baseline also did not differ significantly between two cohorts. However, Asian cohort had higher LDH value (Median LDH Ratio (Q1, Q3), 2.0 (1.1, 5.6) in the Asian cohort and 1.6 (1.0, 3.8) in the non-Asian cohort; p<0.0001) and mean percent GPI-deficient granulocyte clone (50% vs 43%; p=0.0041) compared with non-Asian cohort. In comparison between Asian in Asia cohort and Asian in non-Asia cohort, the difference in mean percent GPI-deficient granulocyte clone remained significant (53% vs 39%; p=0.036). The proportion of patients with a history of major adverse vascular events (MAVE) at baseline was significantly higher in non-Asian cohort than in Asian-cohort (p=0.0005). The significant differences were also observed in all thrombotic events (TE), venous TE, and non-TE MAVE (Fig. 1). However, the proportion of patients with a history of arterial TE was not significantly different between two cohorts, or in comparison between Asians in Asia cohort and Asians in non-Asia cohort (Fig. 2). The proportion of patients with a history of MAVE/TE at baseline did not differ significantly among Japan, Taiwan, and Korea. Regarding the treatment, Asian cohort had more patients with a history of RBC transfusion (67% vs 52%; p=<0.0001) and corticosteroid therapy (47% vs 34%; p=0.0003) than non-Asian cohort, but less patients with a history of anticoagulant therapy such as heparin or warfarin (9% vs 16%; p=0.002) and cyclosporine/ATG (29% vs 42%; p<0.0001). The difference remained significant in the comparison between Asians in Asia and Asians in non-Asia except for the history of cyclosporine/ATG. Regarding the history of physician-reported symptoms, the proportion of patients with easy bruise/bleeding was higher in non-Asian cohort than Asian cohort (38% vs 20%; p<0.0001). The same difference was also observed between Asians in Asia cohort and Asians in non-Asia cohort (15% vs 41%; p=0.0004). Conclusions: This study with large-scale data base strongly suggested that history of MAVE/TE is higher in non-Asian patients with PNH compared with Asian patients. The comparison between Asians in non-Asia and Asians in Asia cohorts suggested that genetic factors rather than life style and diet play a role in developing MAVE/TE in PNH patients. This study also highlighted that the registry data serve as a valuable resources to understand the clinical course of PNH and thus contribute to establish optimal therapeutic approaches according to patient's racial background.

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