A prospective, observational study to evaluate adverse drug reactions in patients with COVID-19 treated with remdesivir or hydroxychloroquine: a preliminary report

Abstract

Objectives Since the outbreak of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the pressure to minimise its impact on public health has led to the implementation of different therapeutic strategies, the efficacy of which for the treatment of coronavirus disease 2019 (COVID-19) was unknown at the time. Remdesivir (REM) was granted its first conditional marketing authorisation in the EU in June 2020. The European Medicines Agency (EMA) and local health authorities all across the EU have since strongly recommended the implementation of pharmacovigilance activities aimed at further evaluating the safety of this new drug. The objective of this study was to evaluate adverse drug reactions (ADRs) attributed to either REM or hydroxychloroquine (HCQ) in patients hospitalised for COVID-19 in Centro Hospitalar de Lisboa Ocidental, a Portuguese hospital centre based in Lisbon. We present the preliminary results reporting plausible adverse effects of either HCQ or REM. Methods An observational cohort study was carried out between 16 March and 15 August 2020. Participants were divided into two cohorts: those prescribed an HCQ regimen, and those prescribed REM. Suspected ADRs were identified using an active monitoring model and reported to the Portuguese Pharmacovigilance System through its online notification tool. The ADR cumulative incidence was compared between the two cohorts. Results The study included 149 patients, of whom 101 were treated with HCQ and the remaining 48 with REM. The baseline characteristics were similar between the two cohorts. A total of 102 ADRs were identified during the study period, with a greater incidence in the HCQ cohort compared with the REM cohort (47.5% vs 12.5%; p<0.001). Causality was assessed in 81 ADRs, all of which were considered possible. Conclusions Real-world data are crucial to further establish the safety profile for REM. HCQ is no longer recommended for the treatment of COVID-19.

Hydroxychloroquine/chloroquine and the risk of acute kidney injury in COVID-19 patients: a systematic review and meta-analysis

“…In addition, four studies [ 24 , 26 , 27 , 38 ] had a possible bias of deviation from the intended intervention, and five [ 29 , 39–42 ] presented some concerns regarding the bias of missing outcomes. For the nine NRSIs, six studies [ 30 , 31 , 34 , 35 , 37 , 43 ] showed a critical bias, three [ 32 , 33 , 36 ] showed moderate bias due to confounding, and four studies [ 31 , 34 , 35 , 37 ] showed moderate bias due to the selection of participants. In addition, three [ 31 , 32 , 36 ] showed critical bias, and three [ 32 , 34 , 43 ] showed moderate bias due to the measurement of outcomes, and one [ 43 ] showed moderate bias due to the selection of the reported result.…”

The Efficacy of Remdesivir in Reducing SARS-CoV-2 Viral Load and Its Safety on COVID-19 Patients: A Systematic Review

“…The incidence of ADR was significantly higher (47.5%) in hydroxychloroquine (as the comparison group in this study) than in RDV (12.5%) (P<0.001). 18 A study conducted in Spain with 123 subjects stated that RDV was used in four subjects with chronic kidney disease and 24 subjects with reduced immunity (13 with solid neoplasms, 8 with hematological disease and 3 with HIV infection).…”

Problems associated with antiviral drugs and vaccines development for COVID-19: approach to intervention using expression vectors via GPI anchor

“…[7,25] The data showed no potential benefits of these drugs for the treatment of COVID-19, and long-term and high-dose of these drugs can cause serious cardiac adverse events. [26,27] Finally, chloroquine and hydroxychloroquine are not approved via the FDA for the treatment of COVID-19. A variety of therapeutic approaches including novel antivirals, modifiers of the immune response or other intrinsic pathways, and combination approach are needed to continue to improve outcomes in patients with COVID-19.…”