EFFICACY, TREATMENT ADMINISTRATION SATISFACTION AND SAFETY OF SUBCUTANEOUS RAVULIZUMAB THROUGH 1 YEAR IN PATIENTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA WHO RECEIVED PRIOR INTRAVENOUS ECULIZUMAB

Background: The efficacy of ravulizumab (intravenous [IV] formulation;administered every 8 weeks) for the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH) has been demonstrated in several randomized trials (NCT02946463, NCT03056040, NCT03406507). In study 303 (NCT03748823), subcutaneous (SC) ravulizumab, administered weekly via an on-body delivery system, showed pharmacokinetic non-inferiority to IV ravulizumab in adult patients with PNH who were clinically stable on prior IV eculizumab treatment. Here, we report results from the first 1 year of SC treatment, starting at day 15 for patients who continued SC ravulizumab during the extension period (SC/SC) and day 71 for patients who switched from IV ravulizumab to SC ravulizumab (IV/SC). Aims: To evaluate the efficacy, treatment administration satisfaction and safety of SC ravulizumab through the first 1 year (day 351) of treatment in adult patients with PNH previously treated with eculizumab. Methods: Patients (≥ 18 years) with clinically stable PNH (lactate dehydrogenase [LDH] levels ≤ 1.5 × upper limit of normal [246 U/L]) and ≥ 3 months prior eculizumab treatment were enrolled in the study, which consisted of a screening period (day-1 to day-30), a 10-week randomized treatment period and an extension period of up to 172 weeks. During the randomized treatment period, patients were assigned (2:1 ratio) to receive either SC ravulizumab or IV ravulizumab;all patients received SC ravulizumab during the extension period. Efficacy endpoints included: change in LDH from baseline;incidence of breakthrough hemolysis;transfusion avoidance;and stabilized hemoglobin (avoidance of a ≥ 2 g/dL decrease in hemoglobin in the absence of transfusion). Treatment administration satisfaction was assessed via the Treatment Administration Satisfaction Questionnaire (TASQ), which has been validated in a PNH population. Safety, including adverse events (AEs), serious AEs (SAEs) and adverse device effects (ADEs), were also assessed up to the 1-year data cut-off. Results: In total, 128 patients received SC ravulizumab (SC/SC: n = 84;IV/SC: n = 44;mean [range] duration of SC treatment: 486.4 [37-709] days). Efficacy endpoints (SC/SC and IV/SC) remained stable over time through 1 year of SC ravulizumab treatment. Mean (standard deviation [SD]) percentage change in LDH from baseline to SC day 351 was 0.9% (20.5%). Breakthrough hemolysis events were infrequent: 5/128 patients (3.9%);no event was considered free C5-related. Transfusion avoidance was maintained in 83.6% of patients during SC treatment, and 79.7% achieved stabilized hemoglobin. Improvement in total TASQ score with SC ravulizumab (compared with baseline IV eculizumab) was apparent at the first post-SC treatment assessment (SC day 29) and maintained until data cut-off (Figure). The most common AEs (reported by ≥ 10% of patients, excluding ADEs related to device product issues) during SC treatment were headache (14.1%, all grade ≤ 2), COVID-19 (14.1%, one death) and pyrexia (10.9%);injection site reaction (4.7%) was the most common non-device related ADE. Treatment-emergent SAEs were experienced by 21.1% of patients through to data cut-off. Although many patients had ≥ 1 device issue ADE, full SC dose administration was achieved in 99.9% of attempts. ADE incidence decreased over time. Image: Summary/Conclusion: The SC method of administration provides an additional treatment option for patients with PNH receiving ravulizumab therapy. Patients may be switched from IV eculizumab or IV ravulizumab to SC ravulizumab without loss of efficacy.

COVID-19 outcome in hemodialysis patients

Introduction and objective: The SARS-CoV -2 epidemic represents a special risk for patients on hemodialysis (HD) due to their comorbidities and the fact that they often have a more severe case of inflammation with fewer symptoms and a worse evolution and outcome. The aim of this study was to detect the clinical and biochemical characteristics of patients on hemodialysis (HD) who presented a suspicious involvement of COVID-19 (Corona Virus Disease – 2019), their risk factors and specific outcomes. Material and methods: This is a retrospective, observational case report study in HD patients suspected of having COVID-19. Records pointed to comorbidities, clinical and laboratory tests, quantitative reverse transcription polymerase chain reaction (RT-qPCR) tests for SARS-COV -2 and outcomes. Descriptive statistics and linear and logistic regression analyses were performed. Results: Of the total number of HD patients (1514), 248 HD patients were suspected to have COVID-19 (106 were positive, 83 were negative and 59 suspected using PCR testing);the median age was 51 years (IR 36-63 years), 54.8% were males, had hypertension (87.5%), with a hemoglobin count of 8.9 g (IR 7.5-10.6 g) and symptoms such as cough, fever and dyspnea (65.7, 64.5 and 53.2%, respectively). The fatality rate in the group of patients with positive RT-qPCR was 29.24%. Conclusions: The mortality and fatality rate is often high in this population. The age group, sex, and cardio-metabolic comorbidities behave similarly to the rest of the non-renal population. Pre-existing biochemical status does not make a difference in the outcome. The predominant symptomatology was pulmonary in nature.

The pandemic helped create solidarity among pavilions

As the most relevant architecture event in the world, the delay of the 17th Venice Biennale – from 2020 to 2021 – was evidence of the magnitude of the COVID-19 pandemic. But this postponement meant not only a pause but also a reformulation of the spirit of this event entitled, in surprising anticipation, “How will we live together.”. © 2021, Pontificia Universidad Catolica de Chile 1. All rights reserved.