PMID- 36506552
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20221221
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 13
DP  - 2022
TI  - Real-world safety of PCSK9 inhibitors: A pharmacovigilance study based on 
      spontaneous reports in FAERS.
PG  - 894685
LID - 10.3389/fphar.2022.894685 [doi]
LID - 894685
AB  - Objective: We aimed to evaluate alirocumab- and evolocumab-related adverse events 
      (AEs) in real-world compared with all other drugs, overall and by gender and age 
      subgroups; we also aimed to compare their risks of cognitive impairment, 
      musculoskeletal disorders and diabetes with various statins and ezetimibe. 
      Methods: We retrospectively extracted AE reports from the FDA Adverse Event 
      Reporting System (FAERS) database during July 2015-June 2021. Disproportionality 
      analyses were performed using reporting odds ratios (RORs) to detect AE signals 
      of alirocumab and evolocumab in the overall population and in different age and 
      gender subgroups, respectively. Results: Compared with all other drugs, both 
      alirocumab and evolocumab had a significant signal in "musculoskeletal and 
      connective tissue disorders" (ROR(1) = 2.626, 95% CI 2.552-2.702; ROR2 = 2.575, 
      95% CI 2.538-2.613). The highest ROR value of 2.311 (95% CI 2.272-2.351) was for 
      "injury, poisoning and procedural complications" and was found in patients aged 
      >/=65 years on evolocumab. The most frequent AEs were "general disorders and 
      administration site conditions" and "musculoskeletal and connective tissue 
      disorders" for all subpopulations. At the preferred term level, the most frequent 
      AE signal was myalgia for alirocumab and injection site pain for evolocumab, 
      overall and by subgroups. Compared with statins/ezetimibe, PCSK9 inhibitors 
      exhibited lower ROR values for adverse events associated with SOC "nervous system 
      disorders", "psychiatric disorders" and "metabolism and nutrition disorders" (all 
      RORs < 1), but mixed results for musculoskeletal disorders. Compared with all 
      other drugs, undocumented AEs, such as acute cardiac event (ROR = 30.0, 95% CI 
      9.4-95.3) and xanthoma (ROR = 9.3, 95% CI 3.4-25.5), were also reported. 
      Conclusion: Real-world evidence showed that PCSK9 inhibitors were associated with 
      an increased risk of musculoskeletal and connective tissue disorders and general 
      disorders and administration site conditions, overall and by subgroups. Muscle 
      toxicity, injection site reactions, and influenza-like illness were significant 
      AE signals. Compared with various statins and ezetimibe, PCSK9 inhibitors have 
      shown a favorable safety profile in muscle-related events, cognitive impairment 
      and diabetes. Some undocumented AE signals were also reported. Due to the 
      limitations of spontaneous reporting databases, further studies are still needed 
      to establish causality and validate our results.
CI  - Copyright (c) 2022 Feng, Li, Tong, He, Zhu, Xiang and Tang.
FAU - Feng, Zhen
AU  - Feng Z
AD  - Department of Clinical Pharmacy and Pharmacy Administration, School of Pharmacy, 
      Fudan University, Shanghai, China.
FAU - Li, Xiaoye
AU  - Li X
AD  - Department of Pharmacy, Zhongshan Hospital, Fudan University, Shanghai, China.
FAU - Tong, Wai Kei
AU  - Tong WK
AD  - Department of Clinical Pharmacy and Pharmacy Administration, School of Pharmacy, 
      Fudan University, Shanghai, China.
FAU - He, Qingfeng
AU  - He Q
AD  - Department of Clinical Pharmacy and Pharmacy Administration, School of Pharmacy, 
      Fudan University, Shanghai, China.
FAU - Zhu, Xiao
AU  - Zhu X
AD  - Department of Clinical Pharmacy and Pharmacy Administration, School of Pharmacy, 
      Fudan University, Shanghai, China.
FAU - Xiang, Xiaoqiang
AU  - Xiang X
AD  - Department of Clinical Pharmacy and Pharmacy Administration, School of Pharmacy, 
      Fudan University, Shanghai, China.
FAU - Tang, Zhijia
AU  - Tang Z
AD  - Department of Clinical Pharmacy and Pharmacy Administration, School of Pharmacy, 
      Fudan University, Shanghai, China.
LA  - eng
PT  - Journal Article
DEP - 20221124
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC9729267
OTO - NOTNLM
OT  - FAERS
OT  - PCSK9 inhibitors
OT  - age-and gender-tailored treatment
OT  - alirocumab
OT  - drug safety
OT  - evolocumab
OT  - pharmacovigilance
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/12/13 06:00
MHDA- 2022/12/13 06:01
PMCR- 2022/11/24
CRDT- 2022/12/12 11:18
PHST- 2022/03/12 00:00 [received]
PHST- 2022/11/15 00:00 [accepted]
PHST- 2022/12/12 11:18 [entrez]
PHST- 2022/12/13 06:00 [pubmed]
PHST- 2022/12/13 06:01 [medline]
PHST- 2022/11/24 00:00 [pmc-release]
AID - 894685 [pii]
AID - 10.3389/fphar.2022.894685 [doi]
PST - epublish
SO  - Front Pharmacol. 2022 Nov 24;13:894685. doi: 10.3389/fphar.2022.894685. 
      eCollection 2022.