Additional clinical data
In addition to data used for model validation, additional data were used
to get some insight on dose-exposure-response as regards clinically
relevant beneficial and toxic effects of HCQ in COVID-19. Even though
these data could not permit a formal exposure-response analysis, they
were used to describe the doses and PK exposure distributions in
COVID-19 patients either with favourable responses (discharge from the
hospital based on criteria described below) or experiencing adverse drug
reactions after treatment with HCQ. Summary level and patient level data
were used for this purpose.
Summary level data
These include data from 3 previously published clinical data in COVID-19
patients treated either with HCQ monotherapy [8-9] or with HCQ
combined with azithromycin (AZM) [7, 10].
Patient level data
Clinical data were obtained from 172 COVID-19 in-patients hospitalised
at Saint-Pierre Hospital in Brussels (Belgium) from
1st of March to 6th of April 2020
and treated with HCQ monotherapy. Summary of patient characteristics as
well as relevant information available on their disease stage and
response to HCQ monotherapy are included in Table 2. Statistical
analysis was performed using SAS JMP v.10 software. Criteria for
hospitalization included COVID-19 suspicion based on radiological
findings in patients with known severity factors (hypertension,
diabetes, lung disease, age >60) and/or with one the
following criteria oxygen desaturation <94% while breathing
ambient air, respiratory rate > 22/min, heart rate
>125, decrease of oxygen saturation <94% after
one minute walking test altered consciousness; The following criteria
were taken into account before discharge: no requirement of oxygen
supplementation, no evidence of desaturation while walking without
oxygen supplementation, ability of oral medication intake and
appropriate condition for isolation at home.
Moreover, EudraVigilance (EV), an European public vigilance database
including spontaneous reports of adverse events with medications, was
consulted and cases related to the use of HCQ in COVID-19 extracted.