Varnost in učinkovitost monoklonskih protiteles za zdravljenje covid-19: sistematični pregled objavljenih raziskav in meta-analiza

Požar, Ana (author), Jeras, Matjaž (mentor), Locatelli, Igor (comentor)

Pandemija COVID-19 je zelo obremenila zdravstveni sistem. Čeprav se COVID-19 v večini primerov izraža v blagi obliki, lahko, še posebej pri pacientih s prisotnimi dejavniki tveganja, poteka v hujši obliki, ki je lahko življenje ogrožajoča. Namen naše naloge je ovrednotiti varnost in učinkovitost posameznih monoklonskih protiteles ali njihovih kombinacij pri zdravljenju ne-hospitaliziranih pacientov s COVID-19, ki imajo vsaj en dejavnik tveganja za težji potek bolezni. Metode: Izvedli smo sistematični pregled literature, in sicer z uporabo prosto dostopnih bibliografskih spletnih zbirk MEDLINE in Google Scholar. V magistrsko nalogo smo vključili raziskave, kjer so spremljali varnost in učinkovitost aplikacije monoklonskih protiteles bamlanivimaba, sotrovimaba in regdanvimaba ter varnost in učinkovitost njihovih kombinacij, in sicer bamlanivimaba in etesevimaba ter casirivimaba in imdevimaba. Magistrska naloga je sestavljena iz dveh delov. V prvem smo izvedli meta-analizo randomiziranih dvojno slepih kliničnih študij s pomočjo programa RevMan, v drugem pa smo ovrednotili varnost in učinkovitost aplikacij monoklonskih protiteles pacientom s COVID-19, ki so bili vključeni v serije primerov oz. v poročila posameznih primerov. Rezultati: S sistematičnim pregledom smo pridobili 9 dvojno slepih randomiziranih kliničnih raziskav s kontrolno skupino. V 5 od teh poročajo o varnosti in učinkovitosti monoterapije z monoklonskimi protitelesi, v 4 pa o varnosti in učinkovitosti njihovih kombinacij. Z meta-analizo smo dokazali, da aplikacija monoklonskega protitelesa v monoterapiji zmanjša število hospitalizacij, RR: 0,35 (95 % CI: 0,23 – 0,52). Tudi kombinacija monoklonskih protiteles je, v primerjavi s placebom, zmanjšala število hospitalizacij, RR: 0,31 in (95 % CI: 0,22 – 0,45). Z meta-analizo pa smo dokazali tudi zmanjšano število smrti ob uporabi kombinacije monoklonskih protiteles v primerjavi s placebom, RR = 0,14 (95 % CI: 0,04 – 0,45). Število in resnost neželenih učinkov pa sta bila v vseh študijah primerljiva med placebo (kontrolno) in eksperimentalno skupino. Sklep: Naši rezultati potrjujejo varnost in učinkovitost monoklonskih protiteles, uporabljenih pri pacientih s COVID-19, ki niso bili hospitalizirani in imajo prisotne dejavnike za težji potek bolezni.

• Language: Slovenian
• Keywords: monoklonska protitelesa, COVID-19, varnost, učinkovitost
• Work type: Master's thesis/paper
• Organization: FFA - Faculty of Pharmacy
• Year: 2022
• PID: 20.500.12556/RUL-143352
• Publication date in RUL: 16.12.2022

Secondary language

• Language: English
• Title: Safety and efficiency of monoclonal antibodies for treatment of covid-19: systematic review and meta-analysis

Abstract

Background: COVID -19 has placed a massive burden on the health care system. COVID -19 progresses mildly in most cases, but can also be severe and life-threatening, especially in patients with existing risk factors. The aim of this master's thesis is to evaluate the safety and efficacy of single monoclonal antibodies or a combination of monoclonal antibodies in non-hospitalised patients who have at least one risk factor for severe COVID -19. Methods: A systematic review of the literature was performed using one of the free online bibliographic databases MEDLINE and Google Scholar. We selected the studies that reported the safety and efficacy of the following antibody monotherapy: bamlanivimab, sotrovimab and regdanvimab, or the following combination of antibodies: bamlanivimab and etesevimab, or casirivimab and imdevimab. The master thesis consists of two parts. In the first part, we performed a meta-analysis using RevMan with data from randomized, double-blind, placebo-controlled clinical trials. In the second part, we evaluated the safety and efficacy of using monoclonal antibodies in patients included in case reports or case series. Results: With a systematic review of the literature, we obtained 9 double-blinded randomized placebo-controlled clinical studies. 5 of them reported the safety and efficacy of the usage of single monoclonal antibodies and 4 reported the safety and efficacy of using a combination of monoclonal antibodies. The meta-analysis showed a reduction in the number of hospitalizations with the application of one monoclonald antibody, RR = 0.35, (95% CI 0.23-0.52). The meta-analysis also showed a reduction in hospitalizations with the use of combinations of monoclonal antibodies, RR: 0.31 (95% CI 0.22 - 0.45). Using meta-analysis, we also demonstrated a reduction in the number of deaths with the application of combination of monoclonal antibodies compared to placebo, RR = 0.14, (95% CI 0.04 - 0.45). The number and severity of adverse effects were comparable in all studies in the treatment and placebo groups. Conclusion: The obtained results confirm safety and efficacy of monoclonal antibodies in non-hospitalized COVID-19 patients, who have present risk factors for severe COVID-19.

• Keywords: monoclonal antibodies, COVID-19, safety, efficiency