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1.
Adv Ther ; 2022 Oct 22.
Article in English | MEDLINE | ID: covidwho-2085581

ABSTRACT

INTRODUCTION: This study compared the pharmacokinetics (PK) of the ravulizumab on-body delivery system for subcutaneous (SUBQ) administration with intravenous (IV) ravulizumab in eculizumab-experienced patients with paroxysmal nocturnal hemoglobinuria (PNH). METHODS: Patients with PNH received SUBQ ravulizumab (n = 90) or IV ravulizumab (n = 46) during the 10-week randomized treatment period; all patients then received SUBQ ravulizumab during an extension period (< 172 weeks; data cutoff 1 year). Primary endpoint was day 71 serum ravulizumab trough concentration (Ctrough). Secondary endpoints were ravulizumab Ctrough and free C5 over time. Efficacy endpoints included change in lactate dehydrogenase (LDH), breakthrough hemolysis (BTH), transfusion avoidance, stabilized hemoglobin, and Treatment Administration Satisfaction Questionnaire (TASQ) score. Safety, including adverse events (AEs) and adverse device effects (ADEs), was assessed until data cutoff. RESULTS: SUBQ ravulizumab demonstrated PK non-inferiority with IV ravulizumab (day 71 SUBQ/IV geometric least-squares means ratio 1.257 [90% confidence interval 1.160-1.361; p < 0.0001]). Through 1 year of SUBQ administration, ravulizumab Ctrough values were > 175 µg/mL (PK threshold) and free C5 < 0.5 µg/mL (PD threshold). Efficacy endpoints remained stable: mean (standard deviation, SD) LDH percentage change was 0.9% (20.5%); BTH events, 5/128 patients (3.9%); 83.6% achieved transfusion avoidance; 79.7% achieved stabilized hemoglobin. Total TASQ score showed improved satisfaction with SUBQ ravulizumab compared with IV eculizumab (mean [SD] change at SUBQ day 351, - 69.3 [80.1]). The most common AEs during SUBQ treatment (excluding ADEs) were headache (14.1%), COVID-19 (14.1%), and pyrexia (10.9%); the most common ADE unrelated to a device product issue was injection site reaction (4.7%). Although many patients had ≥ 1 device issue-related ADE, full SUBQ dose administration was achieved in 99.9% of attempts. CONCLUSIONS: SUBQ ravulizumab provides an additional treatment choice for patients with PNH. Patients may switch to SUBQ ravulizumab from IV eculizumab or ravulizumab without loss of efficacy. TRIAL REGISTRATION: NCT03748823.


Paroxysmal nocturnal hemoglobinuria (PNH) is a rare blood disorder characterized by the destruction of red blood cells (hemolysis) within blood vessels. In addition to hemolysis, patients with PNH are susceptible to life-threatening blood clots (thromboses). Eculizumab and ravulizumab are types of treatments for PNH, called C5 inhibitors. In the blood, these treatments bind to C5 protein and prevent the destruction of red blood cells, reducing the symptoms and complications of PNH. Both treatments are approved for use via intravenous (through the vein) administration. Ravulizumab is also approved in the USA for use via subcutaneous (under the skin) administration. This study compared subcutaneous ravulizumab with intravenous ravulizumab in patients with PNH who had previously been treated with eculizumab. During the initial treatment period of 71 days, 90 patients received subcutaneous ravulizumab and 46 received intravenous ravulizumab. Following this period, all patients received subcutaneous ravulizumab. At day 71, the amount of ravulizumab in the blood of patients taking subcutaneous ravulizumab was no less than in patients taking intravenous ravulizumab and was maintained over 1 year of treatment. Efficacy measures (how well it works) remained stable in patients taking subcutaneous ravulizumab for 1 year and side effects were comparable with those of intravenous ravulizumab. Patients reported more satisfaction with subcutaneous ravulizumab than intravenous eculizumab, as assessed by the Treatment Administration Satisfaction Questionnaire. This study showed that patients with PNH can switch from intravenous eculizumab or ravulizumab to subcutaneous ravulizumab without loss of efficacy. Subcutaneous ravulizumab provides an additional treatment choice for patients with PNH.

2.
Vaccine ; 39(48): 7052-7057, 2021 11 26.
Article in English | MEDLINE | ID: covidwho-1487997

ABSTRACT

Emerging evidence suggest a possible association between immune thrombocytopenia (ITP) and some formulations of COVID-19 vaccine. We conducted a retrospective case series of ITP following vaccination with Vaxzevria ChadOx1-S (AstraZeneca) and mRNA Comirnaty BNT162b2 COVID-19 (Pfizer-BioNTech) vaccines and compare the incidence to expected background rates for Victoria during the first six months of the Australian COVID-19 vaccination roll-out in 2021. Cases were identified by reports to the Victorian state vaccine safety service, SAEFVIC, of individuals aged 18 years or older presenting with thrombocytopenia following COVID-19 vaccination without evidence of thrombosis. Twenty-one confirmed or probable cases of ITP were identified following receipt of AstraZeneca (n = 17) or Pfizer-BioNTech (n = 4) vaccines. This translates to an observed incidence of 8 per million doses for AstraZeneca vaccine, twice the expected background rate of 4.1 per million. The observed rate for Pfizer-BioNTech was consistent with the expected background rate. The median time to onset for the cases post AstraZeneca vaccination was 10 days (range 1-78) and median platelet nadir 5 × 109/L (range 0-67 × 109/L). Hospital presentations or admissions for management of symptoms such as bleeding occurred in 18 (86%) of the cases. The majority of cases (n = 11) required intervention with at least 2 therapy modalities. In conclusion, we observed a substantially higher than expected rate of ITP following AstraZeneca vaccination. ITP is the second haematological adverse event, distinct from that of thrombosis with thrombocytopenia syndrome (TTS), observed following AstraZeneca vaccination.


Subject(s)
COVID-19 , Purpura, Thrombocytopenic, Idiopathic , Thrombocytopenia , Vaccines , COVID-19 Vaccines , Humans , Purpura, Thrombocytopenic, Idiopathic/chemically induced , Purpura, Thrombocytopenic, Idiopathic/epidemiology , Retrospective Studies , SARS-CoV-2 , Vaccination , Victoria/epidemiology
3.
Intern Med J ; 51(8): 1203-1204, 2021 08.
Article in English | MEDLINE | ID: covidwho-1367323

Subject(s)
COVID-19 , Humans , SARS-CoV-2
4.
Intern Med J ; 51(1): 5-6, 2021 01.
Article in English | MEDLINE | ID: covidwho-1314057

Subject(s)
Publishing , Humans
5.
Transplant Cell Ther ; 27(3): 270.e1-270.e6, 2021 03.
Article in English | MEDLINE | ID: covidwho-1108498

ABSTRACT

SARS-CoV-2 has spread rapidly worldwide, but the full impact of the COVID-19 pandemic on the field of hematopoietic cell transplantation (HCT) remains unknown. To understand this better, an 18-item online survey was disseminated by the Worldwide Network for Blood & Marrow Transplantation with questions exploring SARS-CoV-2 testing algorithms, mobilization, and cryopreservation strategies and COVID-19 infections in allogeneic related and autologous hematopoietic progenitor cell (HPC) donors. The aim of this survey was to assess the impact of the outbreak on policies relating to HPC mobilization, collection, and processing with respect to changes in daily routine. A total of 91 individual responses from distinct centers in 6 continents were available for analysis. In these centers, the majority (72%) of allogeneic related and autologous donors are routinely tested for SARS-CoV-2 before HPC collection, and 80% of centers implement cryopreservation of allogeneic HPC grafts before commencing conditioning regimens in patients. Five related and 14 autologous donors who tested positive for COVID-19 did not experience any unexpected adverse events or reactions during growth factor administration (eg, hyperinflammatory syndrome). These data are limited by the small number of survey respondents but nonetheless suggest that centers are following the recommendations of appropriate scientific organizations and provide some preliminary data to suggest areas of further study.


Subject(s)
Bone Marrow Transplantation/statistics & numerical data , COVID-19/epidemiology , Hematopoietic Stem Cell Transplantation/statistics & numerical data , Pandemics , SARS-CoV-2 , Algorithms , Allografts , Bone Marrow Transplantation/trends , COVID-19/diagnosis , COVID-19/prevention & control , COVID-19 Testing/methods , COVID-19 Testing/statistics & numerical data , Cryopreservation/methods , Donor Selection/standards , Global Health , Health Care Surveys , Hematopoietic Stem Cell Mobilization/statistics & numerical data , Hematopoietic Stem Cell Transplantation/trends , Practice Patterns, Physicians'/statistics & numerical data , Procedures and Techniques Utilization/statistics & numerical data , Tissue Preservation/methods , Transplantation, Autologous , Unrelated Donors/statistics & numerical data
7.
Biol Blood Marrow Transplant ; 26(12): 2181-2189, 2020 12.
Article in English | MEDLINE | ID: covidwho-722012

ABSTRACT

The current COVID-19 pandemic, caused by SARS-CoV-2, has impacted many facets of hematopoietic cell transplantation (HCT) in both developed and developing countries. Realizing the challenges as a result of this pandemic affecting the daily practice of the HCT centers and the recognition of the variability in practice worldwide, the Worldwide Network for Blood and Marrow Transplantation (WBMT) and the Center for International Blood and Marrow Transplant Research's (CIBMTR) Health Services and International Studies Committee have jointly produced an expert opinion statement as a general guide to deal with certain aspects of HCT, including diagnostics for SARS-CoV-2 in HCT recipient, pre- and post-HCT management, donor issues, medical tourism, and facilities management. During these crucial times, which may last for months or years, the HCT community must reorganize to proceed with transplantation activity in those patients who urgently require it, albeit with extreme caution. This shared knowledge may be of value to the HCT community in the absence of high-quality evidence-based medicine. © 2020 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.


Subject(s)
Bone Marrow Transplantation , COVID-19/diagnosis , COVID-19/therapy , Hematopoietic Stem Cell Transplantation , SARS-CoV-2 , COVID-19/epidemiology , Humans
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