Evidence map›Paper›PMID 35221289›Full record

ReviewDrug metabolism and disposition: the biological fate of chemicals2022

Adverse Drug Reactions and Toxicity of the Food and Drug Administration-Approved Antisense Oligonucleotide Drugs.

Feryal Alhamadani, Kristy Zhang, Rajvi Parikh, Hangyu Wu, Theodore P Rasmussen, Raman Bahal, Xiao-Bo Zhong, José E Manautou

Open access · greenAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Drug metabolism and disposition: the biological fate of chemicals, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
89citing papers in PubMed, 1 pooled it
15.1field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

89 citing papers in PubMed, 1 synthesis or guideline pooled it, 111 citations in OpenAlex.

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29 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 1 institution in 1 country.

Feryal AlhamadaniDepartment of Pharmaceutical Sciences, School of Pharmacy (F.A., K.Z., H.W., T.P.R., R.B., X.Z., J.E.M.), and Department of Physiology and Neurobiology (R.P.), University of Connecticut, Storrs, Connecticut.
Kristy ZhangDepartment of Pharmaceutical Sciences, School of Pharmacy (F.A., K.Z., H.W., T.P.R., R.B., X.Z., J.E.M.), and Department of Physiology and Neurobiology (R.P.), University of Connecticut, Storrs, Connecticut.
Rajvi ParikhDepartment of Pharmaceutical Sciences, School of Pharmacy (F.A., K.Z., H.W., T.P.R., R.B., X.Z., J.E.M.), and Department of Physiology and Neurobiology (R.P.), University of Connecticut, Storrs, Connecticut.
Hangyu WuDepartment of Pharmaceutical Sciences, School of Pharmacy (F.A., K.Z., H.W., T.P.R., R.B., X.Z., J.E.M.), and Department of Physiology and Neurobiology (R.P.), University of Connecticut, Storrs, Connecticut.
Theodore P RasmussenDepartment of Pharmaceutical Sciences, School of Pharmacy (F.A., K.Z., H.W., T.P.R., R.B., X.Z., J.E.M.), and Department of Physiology and Neurobiology (R.P.), University of Connecticut, Storrs, Connecticut.
Raman BahalDepartment of Pharmaceutical Sciences, School of Pharmacy (F.A., K.Z., H.W., T.P.R., R.B., X.Z., J.E.M.), and Department of Physiology and Neurobiology (R.P.), University of Connecticut, Storrs, Connecticut.
Xiao-Bo ZhongDepartment of Pharmaceutical Sciences, School of Pharmacy (F.A., K.Z., H.W., T.P.R., R.B., X.Z., J.E.M.), and Department of Physiology and Neurobiology (R.P.), University of Connecticut, Storrs, Connecticut jose.manautou@uconn.edu xiaobo.zhong@uconn.edu.
José E ManautouDepartment of Pharmaceutical Sciences, School of Pharmacy (F.A., K.Z., H.W., T.P.R., R.B., X.Z., J.E.M.), and Department of Physiology and Neurobiology (R.P.), University of Connecticut, Storrs, Connecticut jose.manautou@uconn.edu xiaobo.zhong@uconn.edu.
University of Connecticut · US

Funding

The role of lncRNAs in P450-mediated drug metabolism and drug-induced liver injuryR35GM140862 · NIGMS · UNIVERSITY OF CONNECTICUT STORRS · PI ZHONG, XIAO-BO · 2021 to 2025
$2.0M
NIGMS NIH HHS R35 GM140862
6 · The paper itself

Abstract

The market for large molecule biologic drugs has grown rapidly, including antisense oligonucleotide (ASO) drugs. ASO drugs work as single-stranded synthetic oligonucleotides that reduce production or alter functions of disease-causing proteins through various mechanisms, such as mRNA degradation, exon skipping, and ASO-protein interactions. Since the first ASO drug, fomivirsen, was approved in 1998, the U.S. Food and Drug Administration (FDA) has approved 10 ASO drugs to date. Although ASO drugs are efficacious in treating some diseases that are untargetable by small-molecule chemical drugs, concerns on adverse drug reactions (ADRs) and toxicity cannot be ignored. Illustrative of this, mipomersen was recently taken off the market due to its hepatotoxicity risk. This paper reviews ADRs and toxicity from FDA drug labeling, preclinical studies, clinical trials, and postmarketing real-world studies on the 10 FDA-approved ASO drugs, including fomivirsen and pegaptanib, mipomersen, nusinersen, inotersen, defibrotide, eteplirsen, golodirsen, viltolarsen, and casimersen. Unique and common ADRs and toxicity for each ASO drug are summarized here. The risk of developing hepatotoxicity, kidney toxicity, and hypersensitivity reactions co-exists for multiple ASO drugs. Special precautions need to be in place when certain ASO drugs are administrated. Further discussion is extended on studying the mechanisms of ADRs and toxicity of these drugs, evaluating the existing physiologic and pathologic states of patients, optimizing the dose and route of administration, and formulating personalized treatment plans to improve the clinical utility of FDA-approved ASO drugs and discovery and development of new ASO drugs with reduced ADRs. SIGNIFICANCE STATEMENT: The current review provides a comprehensive analysis of unique and common ADRs and the toxicity of FDA-approved ASO drugs. The information can help better manage the risk of severe hepatotoxicity, kidney toxicity, and hypersensitivity reactions in the usage of currently approved ASO drugs and the discovery and development of new and safer ASO drugs.

Indexed as

Chemical and Drug Induced Liver InjuryDrug-Related Side Effects and Adverse ReactionsHumansMorpholinosOligonucleotidesOligonucleotides, AntisenseUnited StatesUnited States Food and Drug AdministrationcasimersenMorpholinosOligonucleotidesOligonucleotides, Antisense

Identifiers

PMID35221289
PMCPMC11022857
OpenAlexW4214596965

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.