Effect of Eculizumab on Physician-Reported Symptoms in the Russian Cohort of the Paroxysmal Nocturnal Hemoglobinuria (PNH) International Registry

Autor: Elena Vinogradova, Andrey Zaritskiy, Tatyana Schneider, Alexey Maschan, A. D. Kulagin, S.P. Yakupova, Tatiana Krinitsina, T S Kaporskaya, Andrey Gavrilenko, Yulia Bogdanova, Elena Shilova, Bulat Bakirov, Igor A. Lisukov, Svetlana Volkova, Viktoria Ustyantseva, Natalia Kosacheva, Boris V. Afanasyev, Sergey Meresiy, Kudrat Abdulkadyrov, Valentina Ivanova, Alexander Rumyantsev, Tatiana Kazankova, Yuriy V. Shatokhin, Ludmila Anchukova
Rok vydání: 2014
Předmět:
Zdroj: Blood. 124:5163-5163
ISSN: 1528-0020
0006-4971
Popis: Background: Paroxysmal nocturnal hemoglobinuria is a rare clonal hematopoietic stem cell disease that can lead to life-threatening complications including thrombotic events (TE), chronic kidney disease (CKD) and pulmonary hypertension. In 2011 the International PNH Registry was implemented in the Russian PNH cohort to assess the natural history of PNH and the effects of treatment with eculizumab. Aims: We aim to evaluate the change from baseline to last follow-up in physician-reported symptoms, LDH and hemoglobin concentration in treated and untreated PNH patients. Design and methods: The international PNH Registry is a non-interventional, prospective, multicenter observational study. The study population of this analysis comprised the Russian cohort of the Registry: all patients had a confirmed diagnosis of PNH according to international guidelines. As per local guidelines, blood transfusion dependency and a history of TE were the main indications for treatment with eculizumab. Data are presented as descriptive statistics only. The reporting period includes time from baseline until the earliest of: death; bone marrow transplant; discontinuation from the Registry; discontinuation from eculizumab; last follow-up in the Registry. Results: As of June 2014, the international PNH Registry has enrolled 479 patients from Russia, 75 patients were ever-treated with eculizumab (15.7%), among whom 60 had available data. The median (range) duration of follow-up of patients after eculizumab treatment was 0.8 (-0.7 – 1.9) years and the median years (range) from disease onset to the start of eculizumab treatment was 8.1 (1 – 30) years. One patient discontinued treatment due to the disappearance of PNH clones and disease manifestations. Fifteen deaths were reported during the reporting period; all in patients never treated with eculizumab. | | All patients (N = 464) | Ever-treated with Eculizumab (N = 60) | Never-treated patients (N = 404) | | ---------------------------------------- | ------------------------------- | ---------------------------------------------- | ---------------------------------------- | | History of BMD, n (%) | 423* 313 (74) ongoing | 39* 12 (31) ongoing | 384* 301 (78) ongoing | | History of TE, n (%) | 436* 30 (7) | 39* 9 (23) | 397* 21 (5) | | History of any RBC transfusion, n (%) | 385* 300 (78) | 39* 26 (67) | 346* 274 (79) | | RBC transfusion in past 12 months, n (%) | 419* 245 (59) | 29* 22 (76) | 390* 223 (57) | | History of CKD, n (%) | 435* 24 (6) | 39* 1 (3) | 396* 23 (6) | | History of pulmonary hypertension, n (%) | 435* 11 (3) | 39* 4 (10) | 396* 7 (2) | Table 1. History of medical events at baseline *number of patients with available data | | All patients | Ever-treated with eculizumab | Never-treated patients | | ----------------------------------------------------------------------------- | ----------------------------------------------------- | --------------------------------------------------- | ----------------------------------------------------- | | Abdominal pain, n (%): Improved No change Worsened | N=196 33 (17) 145 (74) 18 (9) | N=29 15 (52) 10 (35) 4 (14) | N=167 18 (11) 135 (81) 14 (8) | | Dysphagia, n (%): Improved No change Worsened | N=195 17 (9) 162 (83) 16 (8) | N=29 7 (24) 20 (69) 2 (7) | N=166 10 (6) 142 (86) 14 (8) | | Dyspnea, n (%): Improved No change Worsened | N=196 55 (28) 127 (65) 14 (7) | N=29 15 (52) 12 (41) 2 (7) | N=167 40 (24) 115 (69) 12 (7) | | Fatigue, n (%): Improved No change Worsened | N=199 23 (12) 169 (85) 7 (4) | N=29 4 (14) 25 (86) – | N=170 19 (11) 144 (85) 7 (4) | | Hemoglobinuria, n (%): Improved No change Worsened | N=196 29 (15) 156 (80) 11 (6) | N=28 12 (43) 16 (57) – | N=168 17 (10) 140 (83) 11 (7) | Table 2. Change from baseline to last follow up for physician-reported symptoms Median (Q1, Q3) Hb concentrations at baseline in ever-treated and never-treated patients were 7.3 (6.3, 9.2) g/dL and 9.0 (7.2, 11.3) g/dL, respectively, and median (Q1, Q3) changes in Hb concentration from baseline to last follow up were 2.1 (1.2, 3.8) g/dL and 0.75 (-0.4, 2.5) g/dL, respectively. Median (Q1, Q3) LDH level at baseline in ever-treated and never-treated patients were 6.0 (3.6, 8.7) x the upper limit of normal (ULN) and 1.1 (0.8, 1.8) x ULN, respectively, and median (Q1, Q3) changes in LDH level from baseline to last follow up were -4.8 (-6.9, -1.9) and 0.0 (-0.2, 0.3) x ULN, respectively. Conclusion: This analysis represent the first report on longitudinal outcomes during eculizumab therapy in Russian patients included in the international PNH Registry and are considered essential for planning patients' follow-up, including monitoring of therapeutic effects and prophylaxis against break-through hemolysis. Overall, the data show an improvement in physician-reported symptoms and reduced hemolysis, as measured by plasma LDH level, in patients treated for a relatively short period of time. Disclosures Lisukov: Alexion: Honoraria. Kulagin: Alexion: Honoraria. Shilova: Alexion: Honoraria. Afanasyev: Alexion: Honoraria.
Databáze: OpenAIRE
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