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

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.

A retrospective observational study of low-level viraemia and its immunological and virological significance: which outcome to expect.

INTRODUCTION: Low-level viraemia (LLV) is observed in some patients with HIV-1 infection on stable antiretroviral therapy (ART). The significance of these findings remains controversial as it conflicts with traditional optimal clinic outcome. This study aims to evaluate the effect of LLV on the establishment of virological failure (VF) and immune deterioration. METHODS: Retrospective observational study of a cohort of HIV-1 infected patients of an Infectious Diseases Clinic, who presented an HIV-1 viral load of 20 to 200 cp/mL, during the year 2012. Patients who were not on ART or non-adherent in the previous 6 months were excluded. Compliance was quantified by clinical and pharmaceutical records. Adherence was defined as ≥95% compliance rate. Demographic, clinical, immunological and therapeutic data were collected from clinical records. LLV was defined as a range of 20-200 cp/mL and stratified as transient (T-LLV): only one measurement, persistent (P-LLV): 2 consecutive measurements with an interval ≥3 months and recurrent (R-LLV): ≥1 T-LLV during an 18-month follow-up. Statistical analysis was performed with Microsoft Office® - Excel 2012. Kolmogorov-Smirnov test, t-test and chi-square test were performed for a significant p value <0.05. RESULTS: During 2012, 2161 HIV-1 infected patients were evaluated at our Clinic, 93% of which were on ART. LLV was documented in 378 (19%), adherence was verified in 151 (52%). The analysis of this cohort (n=151) revealed: 77 (51%) T-LLV, 13 (8.6%) R-LLV and 61 (40%) P-LLV. Mean viral load was 46 cp/mL. Mean TCD4 count was 665 cells/µL with a variation of +63 cells/µL during the study period. There was no VF documented. ART regimens were switched in 16 (11%) patients. Gastrointestinal disturbance was found in 13 (9%). Analysis showed no statistical differences between the analyzed variables (CD4 variation, time of diagnosis and treatment, duration of LLV persistence (less than or more than one year), number of ART regimens, ART regimen and type of NRTI backbone) for all groups (T-LLV, R-LLV, P-LLV), except for mean viral load that showed significant superiority in the T-LLV(38 cp/mL) and R-LLV(36 cp/mL) vs P-LLV(58 cp/mL) (p=0.01 and p<0.01, respectively). CONCLUSIONS: The absence of significant differences in immunological and virological outcomes in this cohort and the absence of VF in all groups, suggests a scarce impact of LLV in patient's prognosis. Prospective studies, with longer follow-up could bring more accurate information.

Time-dependent endpoints as predictors of overall survival in multiple myeloma.

BACKGROUND: Supporting health care sector decisions using time-dependent endpoints (TDEs) such as time to progression (TTP), progression-free survival (PFS), and event-free survival (EFS) remains controversial. This study estimated the quantitative relationship between median TDE and median overall survival (OS) in multiple myeloma (MM) patients. METHODS: Studies (excluding allogeneic transplantation) published from 1970 to 2011 were systematically searched (PubMed). The nonparametric Spearman's rank correlation coefficient measured the association between median TDE and OS. The quantitative relationship between TDEs and OS was estimated with a two-step approach to a simultaneous Tobit model. RESULTS: We identified 153 studies: 230 treatment arms, 22,696 patients and mean study duration of 3.8 years. Mean of median TDEs was 22.5 months and median OS was 39.1 months. Correlation coefficients of median TTP, PFS, and EFS with median OS were 0.51 (P = 0.003), 0.75 (P < 0.0001), and 0.84 (P < 0.0001), respectively. We estimate a 2.5 month (95% confidence interval, 1.7-3.2) increase in median OS for each additional month reported for median TDEs. There was no evidence that this relationship differed by type of surrogate. CONCLUSION: TDEs predict OS in MM patients; this relationship may be valuable in clinical trial design, drug comparisons, and economic evaluation.