Unit:
Κατεύθυνση Κλινική ΦαρμακευτικήLibrary of the School of Science
Supervisors info:
Αριστείδης Δοκουμετζίδης, Αναπληρωτής Καθηγητής Τομέα Φαρμακευτικής Τεχνολογίας, Τμήμα Φαρμακευτικής, Σχολή Θετικών Επιστημών, Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών
Μαρία Βερτζώνη, Αναπληρώτρια Καθηγήτρια Τομέα Φαρμακευτικής Τεχνολογίας, Τμήμα Φαρμακευτικής, Σχολή Θετικών Επιστημών, Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών
Γεωργία Βαλσαμή, Καθηγήτρια Τομέα Φαρμακευτικής Τεχνολογίας, Τμήμα Φαρμακευτικής, Σχολή Θετικών Επιστημών, Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών
Original Title:
Μελέτη της επίδρασης της έκθεσης στο ανακίνρα στην κλινική έκβαση της θεραπείας COVID-19 σε ασθενείς της κλινικής μελέτης φάσεως ΙΙΙ SAVE-MORE.
Translated title:
Study of the effect of exposure to anakinra to clinical outcome of COVID-19 patients who participated in the SAVE-MORE phase III clinical trial.-
Summary:
405 COVID-19 patients were randomized to the anakinra arm in the context of
their participation in the double blind randomized phase III clinical trial SAVEMORE. These patients received daily one subcutaneous injection containing
100 mg of anakinra for 7 – 10 days (depending on how many days they were
hospitalized). Even if all patients received the same daily dose of study drug,
i.e. 100 mg, anakinra clearance appeared to be different among different
patients. As a result, each patient was exposed to different amount of study
drug. Multiple factors, such as disease severity at the timepoint of start of study
treatment and clinical covariates which affect renal excretion rate (i.e. gender,
age, commorbidities, etc.) contributed to intersubject variability of anakinra
clearance. It is important that the mechanism of this interaction is investigated
more.
This bachelor thesis aims to primarily assess if the clearance of anakinra
exhibited statistically significant effect on the clinical outcome of the patients
treated with that, and if yes in which manner and secondarily to examine the
contribution of the covariates that affected renal excretion of anakinra to the
clinical outcome. Clinical outcome was expressed as the event of appearance
of severe respiratory failure (SRF) or the absence of it until Day 14 after the
start of treatment with the study drug.
Clearance of anakinra values ranged between 5.10 (L/h) – 9,20 (L/h) (mean:
6.83 L/h, SD: 0.64). For patients with a higher clearance of anakinra (CL/F ≥
6.5 L/h), the ratio of patients who presented with SRF until Day 14 to patients
who did not was 2.8 times greater (OR = 2.80, 95% CI: 1.50 - 5.40, p < 0.001)
to the same ratio for the patients with a lower clearance of anakinra (CL/F < 6.5
L/h).
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Effect of various factors to both anakinra clearance and clinical outcome was
studied too. It seems that gender, age and commorbidities may affect anakinra
clearance but they were not statistically significantly correlated to clinical
outcome.
When anakinra clearance effect on disease progress on Day 7 was examined,
it was shown that for the patients with higher excretion rate, the ratio of patients
that did not appear with improved clinical condition on Day 7 to those who
appeared with clinical improvement on Day 7 was 1.68 times greater (OR: 1.68,
CI: 1.06 – 2.66) than the same ratio for the patients with lower anakinra
clearance. Correlation analysis between progress disease on Day 7 and clinical
outcome on Day 14 indicated that for patients who were not clinically improved
on Day 7 the ratio of patients who presented with SRF until Day 14 to those
who did not is 4.95 times greater (OR = 4.95, CI: 2.91 – 8.41, p < 0.001) than
the same ratio for the patients who were indeed clinically improved on Day 7.
Clinical improvement comparatively to baseline state was expressed as a
positive difference of SOFA scores for the Days 1 and 7 (SOFA1 – SOFA7 ≤ 0)
Finally, an interesting finding that was extracted by the statistical analyses was
that the two risk factors, that is to say higher anakinra clearance (CL/F ≥ 6.5
L/h) and absence of clinical improvement on Day 7, exhibit a possible
synergistic effect to the event of SRF appearance until Day 14. This statement
was supported by the finding that for the patients who were exposed to both
risk factors, i.e. higher anakinra clearance (CL/F ≥ 6.5 L/h) and absence of
clinical improvement on Day 7, the ratio of patients who presented with SRF
until Day 14 to those who did not was 8.06 times greater than the same ratio
for the patients who were not exposed to any of these two conditions.-
Main subject category:
Science
Keywords:
Anakinra, Clearance, Renal clearance, Anakinra clearance, COVID-19, SAVEMORE, Pharmacokinetics, Pharmacodynamics, Dose – Exposure – Response, SOFA score, Severe Respiratory Failure, Synergistic effect
