Prijava nuspojava cjepiva i lijekova protiv COVID-19 iz Food and Drug Administration Adverse Event Reporting System i EudraVigilance tijekom pandemije COVID-19

Objectives: The aims of this study were to determine whether there are differences in the frequency of adverse events (AEs) from COVID-19 vaccines compared to widely issued vaccines and from COVID-19 drugs in contrast to a widely prescribed drug reported to the FDA Adverse Event Reporting System (FAERS) or EudraVigilance (EV) during the COVID- 19 pandemic. Materials and methods: The FAERS and EV adverse event databases were searched for adverse event reports filed in the U.S. and EU from November 2019 to March 2022. We included all COVID-19 vaccines and drugs which have been approved or emergency use authorized by both the FDA and EMA as of March 31, 2022. The numbers of AEs (serious or non-serious) and the numbers of reaction groups of AEs from Comirnaty (Pfizer-BioNTech), Spikevax (Moderna), or Jcovden (Janssen) COVID-19 vaccines were compared to tetanus and human papillomavirus (HPV) vaccines from January 2021 to March 2022 separately in FAERS and EV. The numbers of AEs (serious or non-serious) and the numbers of reaction groups of AEs from remdesivir, nirmatrelvir/ritonavir, tocilizumab, tixagevimab/cilgavimab, sotrovimab, or casirivimab/imdevimab were compared to methotrexate during three time periods: pre-pandemic (November 7, 2019, to January 29, 2020), first wave (January 30, 2020, to July 15, 2020), and subsequent waves (July 16, 2020, to March 31, 2022). Results: In both the FAERS and EV databases, there was no statistical difference in the number of serious or non-serious AEs from the COVID-19 vaccines compared to the tetanus and HPV vaccines (P=0.406 for both comparisons), although numbers of reported AEs from COVID-19 vaccines are higher in both databases. The median number of serious AEs from COVID-19 vaccines was greater in the FAERS database than in the EV database (94 ([IQR 17-1575]) vs. 11131 ([IQR 120-161077]) although this comparison did not reach statistical significance (P=0.077). For non-serious AEs from COVID-19 vaccines, the EV database reported a greater median number (17376 [IQR 209-251219]) compared to the FAERS database (59 [IQR 21- 429]). There were more serious AEs recorded for methotrexate (median 14601 [IQR 8899- 26493]) compared to the COVID-19 drugs (P=0.047) in the FAERS database, while in the EV database there were more both serious and non-serious AEs for methotrexate (median 5370 [IQR 3868-12883]); P=0.026 and median 754 [IQR 672-1649]; P=0.043, respectively). There was a median of 1755 (IQR 297-7980) serious and 1191 (IQR 370-1821) non-serious AEs from COVID-19 drugs in the FAERS database (P=0.018 and P=0.002, respectively) in the subsequent waves of COVID-19 than in the pre-pandemic and first wave. Similarly, there was a median of 234 (IQR 145-3576) serious and 97 (IQR 45-476) non-serious AEs for COVID- 19 drugs in the EV database (both P=0.002) respectively) in the subsequent waves of COVID- 19 than in the pre-pandemic and first wave. Conclusions: Adverse event reporting systems are important and beneficial tools for pharmacovigilance. Reporting of AEs from COVID-19 vaccines has been significantly high, which may indicate a rise in safety issues and concomitant AEs or a change in reporting behavior or both, while reporting of AEs from COVID-19 drugs has been low, which may indicate that the safety profile of the COVID-19 drugs is sufficient, that the overall use of these drugs is rather low or at least lower than methotrexate, or that reporting behavior is insufficient. Among the two databases, reporting of AEs from COVID-19 vaccines has been higher in the EV database than in the FAERS database, and, in contrast, reporting of AEs of COVID-19 drugs has been higher in the FAERS database than in the EV database for the investigated period. Generally, reporting of AEs has not relevantly changed during the COVID-19 pandemic, although the introduction of COVID-19 vaccines and mass-vaccinations worldwide likely led to stimulated reporting of vaccine AEs, while general under-reporting likely still prevails. Our results may indicate a deficit in the U.S. reporting behavior of AEs following vaccine administration, but this requires further investigation.Ciljevi: Ciljevi ove studije bili su utvrditi postoje li razlike u učestalosti nuspojava od cjepiva protiv COVID-19 u usporedbi na obično korištena cjepiva i od lijekova za COVID-19 u usporedbi na obično propisani lijek koji je prijavljen FDA Adverse Event Reporting System (FAERS) ili EudraVigilance (EV) tijekom pandemije COVID-19. Materijali i metode: U bazama podataka o štetnim događajima FAERS i EV pretražene su prijave štetnih događaja podnesenih u SAD-u i EU od studenog 2019. do ožujka 2022. Uključili smo sva cjepiva protiv COVID-19 i lijekove koje su FDA i EMA odobrili ili odobrili za hitne slučajeve od 31. ožujka 2022. Broj nuspojava (ozbiljnih ili neozbiljnih) i brojevi reakcijskih skupina nuspojava iz Comirnaty (Pfizer-BioNTech), Spikevax (Moderna) ili Jcovden (Janssen) cjepiva protiv COVID-19 uspoređeni su s cjepivima protiv tetanusa i humanog papiloma virusa (HPV) od siječnja 2021. do ožujka 2022. zasebno u FAERS-u i EV. Broj nuspojava (ozbiljnih ili neozbiljnih) i broj reakcijskih skupina nuspojava remdesivira, nirmatrelvira/ritonavira, tocilizumaba, tixagevimaba/cilgavimaba, sotrovimaba ili casirivimaba/imdevimaba uspoređen je s metotreksatom tijekom tri vremenska razdoblja: prije pandemije (7. studenog 2019. do 29. siječnja 2020.), prvi val (30. siječnja 2020. do 15. srpnja 2020.) i sljedeći valovi (16. srpnja 2020. do 31. ožujka 2022.). Rezultati: U bazama podataka FAERS i EV, nije bilo statističke razlike u broju ozbiljnih ili neozbiljnih nuspojava od cjepiva protiv COVID-19 u usporedbi s cjepivima protiv tetanusa i HPV-a (P=0,406 za obje usporedbe), iako je broj prijavljenih nuspojava od cjepiva protiv COVID-19 viši u obje baze podataka. Medijan broja ozbiljnih nuspojava od cjepiva protiv COVID-19 bio je veći u bazi podataka FAERS nego u bazi podataka EV (94 ([IQR 17-1575]) naspram 11131 ([IQR 120-161077]) iako ova usporedba nije dosegla statističku značajnost (P=0,077). Za neozbiljne nuspojave od cjepiva protiv COVID-19, baza podataka EV prijavila je veći srednji broj (17376 [IQR 209-251219]) u usporedbi s bazom podataka FAERS (59 [IQR 21-429]). Bilo je više ozbiljnih nuspojava zabilježenih za metotreksat (medijan 14601 [IQR 8899-26493]) u usporedbi s lijekovima protiv COVID-19 (P=0,047) u bazi podataka FAERS, dok je u bazi podataka EV bilo više i ozbiljnih i neozbiljnih nuspojava za metotreksat (medijan 5370 [IQR 3868-12883]); P=0,026 i medijan 754 [IQR 672-1649]; P=0,043, redom). Postojao je medijan od 1755 (IQR 297-7980) ozbiljnih i 1191 (IQR 370-1821) neozbiljnih nuspojava uzrokovanih lijekovima protiv COVID-19 u bazi podataka FAERS (P=0,018 odnosno P=0,002) u narednim COVID-19 valovima nego u razdoblju prije pandemije i prvom valu. Slično tome, postojao je medijan od 234 (IQR 145-3576) ozbiljnih i 97 (IQR 45-476) neozbiljnih nuspojava za lijekove protiv COVID-19 u EV bazi podataka (oba P=0,002) u narednim COVID-19 valovima nego u razdoblju prije pandemije i prvom valu. Zaključci: Sustavi za prijavu nuspojava važni su i korisni alati za farmakovigilanciju. Prijavljivanje nuspojava od cjepiva protiv COVID-19 bilo je značajno visoko, što može ukazivati na porast sigurnosnih problema i pratećih nuspojava ili promjenu ponašanja pri prijavljivanju ili oboje, dok je prijavljivanje nuspojava od lijekova protiv COVID-19 bilo nisko, što može ukazivati na to da sigurnosni profil lijekova za COVID-19 je dovoljan, da je ukupna upotreba ovih lijekova prilično niska ili barem niža od metotreksata, ili da je ponašanje prijavljivanja nedovoljno. Među dvjema bazama podataka, prijava nuspojava od cjepiva protiv COVID-19 bila je veća u bazi podataka EV nego u bazi podataka FAERS, a, nasuprot tome, prijava nuspojava lijekova protiv COVID-19 bila je veća u bazi podataka FAERS nego u bazi podataka EV za istraživano razdoblje. Općenito, prijavljivanje štetnih događaja nije se značajno promijenilo tijekom pandemije COVID-19, iako je uvođenje cjepiva protiv COVID- 19 i masovnih cijepljenja u cijelom svijetu vjerojatno dovelo do poticanog prijavljivanja štetnih događaja cjepiva, dok općenito nedovoljno prijavljivanje vjerojatno i dalje prevladava. Naši rezultati mogu ukazivati na deficit u izvještavanju o ponašanju štetnih događaja nakon primjene cjepiva u SAD-u, ali to zahtijeva daljnje istraživanje