Injection site reactions after subcutaneous oligonucleotide therapy

van Meer, Leonie; Moerland, Matthijs; Gallagher, Jolie; van Doorn, Martijn B. A.; Prens, Errol P.; Cohen, Adam F.; Rissmann, Robert; Burggraaf, Jacobus

doi:10.1111/bcp.12961

Cited by 45Intramuscular injections and effectsRNA Interference and Gene DeliveryBiosimilars and Bioanalytical Methods

Injection site reactions after subcutaneous oligonucleotide therapy

Open access

van Meer, Leonie, Moerland, Matthijs, Gallagher, Jolie, van Doorn, Martijn B. A., Prens, Errol P., Cohen, Adam F., Rissmann, Robert, Burggraaf, Jacobus·2016·British Journal of Clinical Pharmacology

DOI 10.1111/bcp.12961PMC PMC4972150

Open this paper in CoChat — free account Open PDF

Abstract

Oligonucleotides (ONs) are short fragments of nucleic acids, currently being investigated as therapeutic agents. When administered subcutaneously (sc), ONs cause a specific local reaction originating around the injection site, such as erythema, itching, discomfort and pain, including more severe manifestations such as ulceration or necrosis. These injection site reactions (ISRs) are common, but rather poorly described in the literature. With this review, we aim to provide an overview on the extent of the problem of ISRs, based on reported incidence. A structured literature search was performed to identify reported incidence and clinical features of ISRs which yielded 70 manuscripts that contained information regarding ISRs. The data from literature was combined with data on file available at our institution. All sc administered ONs described in the literature lead to the occurrence of ISRs. The percentage of trial subjects that developed ISRs ranged from 22 to 100% depending on ON. The majority of ONs caused ISRs in more than 70% of the trial subjects. The severity of the observed reactions varied between different ONs. Occurrence rate as well as severity of ISRs increases with higher doses. For chemistry and target of the compounds, no clear association regarding ISR incidence or severity was identified. All ONs developed to date are associated with ISRs. Overcoming the problem of ISRs might add greatly to the potential success of sc‐administered ONs. Knowledge of these skin reactions and their specific immunostimulatory properties should be increased in order to obtain ONs that are more suitable for long‐term use and clinically applicable in a broader patient population.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1111/bcp.12961

Cites

95 of 95 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Recall injection site reactions have been reported with mipomersen, an antisense oligonucleotide targeting ApoB.
“Injection site reactions were more common at higher total monthly doses, as were recall injection site reactions, which have not previously been seen with vupanorsen, but have been reported with mipomersen, an antisense oligonucleotide targeting ApoB.18”
From Effect of Vupanorsen on Non–High-Density Lipoprotein Cholesterol Levels in Statin-Treated Patients With Elevated Cholesterol: TRANSLATE-TIMI 70 (2022) · cites this paper as [18]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Treatment of HCV Infection by Targeting MicroRNA
Janssen, H. L. A., Reesink, H. W., Lawitz, E., Zeuzem, S., Rodriguez‐Torres, M., Patel, K., van der Meer, A. J., Patick, A. K., Chen, A. P., Zhou, Y., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1209026 · Cited by 2,206 · see citing works
Mipomersen, an apolipoprotein B synthesis inhibitor, for lowering of LDL cholesterol concentrations in patients with homozygous familial hypercholesterolaemia: a randomised, double-blind, placebo-controlled trial
Raal, F. J., Santos, R. D., Blom, D. J., Marais, A. D., Charng, M., Cromwell, W. C., Lachmann, R., Gaudet, D., Tan, J. L., Chasan-Taber, S., et al. (2010) · The Lancet · doi:10.1016/s0140-6736(10)60284-x · Cited by 921 · see citing works
Immune surveillance in the skin: mechanisms and clinical consequences
Kupper, T. S., & Fuhlbrigge, R. C. (2004) · Nature reviews. Immunology · doi:10.1038/nri1310 · Cited by 805 · see citing works
Local Dystrophin Restoration with Antisense Oligonucleotide PRO051
van Deutekom, J. C., Janson, A. A. M., Ginjaar, I. B., Frankhuizen, W. S., Aartsma-Rus, A. M., Bremmer-Bout, M., den Dunnen, J. T., Koop, K., van der Kooi, A. J., Goemans, N., et al. (2007) · New England Journal of Medicine · doi:10.1056/nejmoa073108 · Cited by 780 · see citing works
Antisense oligonucleotides: basic concepts and mechanisms.
Dias, N., & Stein, C. A. (2002) · PubMed · Cited by 744 · see citing works
Delayed Drug Hypersensitivity Reactions
Pichler, W. J. (2003) · Annals of Internal Medicine · doi:10.7326/0003-4819-139-8-200310210-00012 · Cited by 737 · see citing works
Systemic Administration of PRO051 in Duchenne's Muscular Dystrophy
Goemans, N., Tulinius, M., van den Akker, J. T., Burm, B. E. A., Ekhart, P. F., Heuvelmans, N., Holling, T. M., Janson, A. A. M., Platenburg, G. J., Sipkens, J. A., et al. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1011367 · Cited by 678 · see citing works
Factor XI Antisense Oligonucleotide for Prevention of Venous Thrombosis
Buller, H. R., Bethune, C., Bhanot, S., Gailani, D., Monia, B. P., Raskob, G. E., Segers, A. E. M., Verhamme, P. B., & Weitz, J. I. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1405760 · Cited by 637 · see citing works
Targeting APOC3 in the familial chylomicronemia syndrome
Gaudet, D., Brisson, D., Tremblay, K., Alexander, V. J., Singleton, W., Hughes, S. G., Geary, R. S., Baker, B. F., Graham, M. J., Crooke, R. M., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1400284 · Cited by 491 · see citing works
Chemosensitisation of malignant melanoma by BCL2 antisense therapy
Jansen, B., Wacheck, V., Heere‐Ress, E., Schlagbauer‐Wadl, H., Höeller, C., Lucas, T., Hoermann, M., Hollenstein, U., Wolff, K., & Pehamberger, H. (2000) · The Lancet · doi:10.1016/s0140-6736(00)03207-4 · Cited by 481 · see citing works
Postinflammatory hyperpigmentation: a review of the epidemiology, clinical features, and treatment options in skin of color.
Davis, E. C., & Callender, V. D. (2010) · PubMed Central · Cited by 410 · see citing works
Antisense oligonucleotide inhibition of apolipoprotein C-III reduces plasma triglycerides in rodents, nonhuman primates, and humans
Graham, M. J., Lee, R. G., Bell, T. A., Fu, W., Mullick, A. E., Alexander, V. J., Singleton, W., Viney, N., Geary, R., Su, J., et al. (2013) · Circulation Research · doi:10.1161/circresaha.111.300367 · Cited by 377 · see citing works
Potent Reduction of Apolipoprotein B and Low-Density Lipoprotein Cholesterol by Short-Term Administration of an Antisense Inhibitor of Apolipoprotein B
Kastelein, J. J. P., Wedel, M. K., Baker, B. F., Su, J. Q., Bradley, J. D., Yu, R. Z., Chuang, E., Graham, M. J., & Crooke, R. M. (2006) · Circulation · doi:10.1161/circulationaha.105.606442 · Cited by 356 · see citing works
Safety and efficacy of drisapersen for the treatment of Duchenne muscular dystrophy (DEMAND II): an exploratory, randomised, placebo-controlled phase 2 study
Voït, T., Topaloğlu, H., Straub, V. W., Francesco Muntoni, A., Deconinck, N., Campion, G., de Kimpe, S. J., Eagle, M., Guglieri, M., Hood, S. R., et al. (2014) · The Lancet Neurology · doi:10.1016/s1474-4422(14)70195-4 · Cited by 305 · see citing works
The DNA Sugar Backbone 2′ Deoxyribose Determines Toll-like Receptor 9 Activation
Haas, T. L., Metzger, J., Schmitz, F., Heit, A., Müller, T. R., Latz, E., & Wagner, H. (2008) · Immunity · doi:10.1016/j.immuni.2008.01.013 · Cited by 298 · see citing works
Apolipoprotein B Synthesis Inhibition With Mipomersen in Heterozygous Familial Hypercholesterolemia
Stein, E. A., Dufour, R., Gagné, C., Gaudet, D., East, C. A., Donovan, J. M., Chin, W., Tribble, D. L., & McGowan, M. P. (2012) · Circulation · doi:10.1161/circulationaha.112.104125 · Cited by 297 · see citing works
Crosstalk pathways between Toll-like receptors and the complement system
Hajishengallis, G., & Lambris, J. D. (2010) · Trends in Immunology · doi:10.1016/j.it.2010.01.002 · Cited by 277 · see citing works
The Role of Environmental Carcinogens, Viruses, and Genetic
Powers, A. A., & Carbone, M. (2002) · Cancer Biology & Therapy · doi:10.4161/cbt.1.4.4 · Cited by 276 · see citing works
Histopathology of Preclinical Toxicity Studies: Interpretation and Relevance in Drug Safety Evaluation
Greaves, P. (1990) · Cited by 262 · see citing works
Mipomersen, an Apolipoprotein B Synthesis Inhibitor, Reduces Atherogenic Lipoproteins in Patients With Severe Hypercholesterolemia at High Cardiovascular Risk
Thomas, G. S., Cromwell, W. C., Ali, S., Chin, W., Flaim, J. D., & Davidson, M. (2013) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2013.07.081 · Cited by 245 · see citing works
Locked Nucleic Acids: Promising Nucleic Acid Analogs for Therapeutic Applications
Veedu, R. N., & Wengel, J. (2010) · Chemistry & Biodiversity · doi:10.1002/cbdv.200900343 · Cited by 241 · see citing works
Randomized, Placebo-Controlled Trial of Mipomersen in Patients with Severe Hypercholesterolemia Receiving Maximally Tolerated Lipid-Lowering Therapy
McGowan, M. P., Tardif, J., Češka, R., Burgess, L. J., Soran, H., Gouni‐Berthold, I., Wagener, G., & Chasan-Taber, S. (2012) · PLoS ONE · doi:10.1371/journal.pone.0049006 · Cited by 222 · see citing works
Antisense Drug Technology: Principles, Strategies, and Applications
Szymkowski, D. E. (2002) · Drug Discovery Today · doi:10.1016/s1359-6446(01)02123-7 · Cited by 221 · see citing works
Phase II Trial of a Toll-Like Receptor 9–Activating Oligonucleotide in Patients With Metastatic Melanoma
Pashenkov, M. V., Goess, G., Wagner, C., Hörmann, M., Jandl, T., Moser, A., Britten, C. M., Smolle, J., Koller, S. H., Mauch, C., et al. (2006) · Journal of Clinical Oncology · doi:10.1200/jco.2006.07.9129 · Cited by 211 · see citing works
Activation of the Alternative Pathway of Complement by a Phosphorothioate Oligonucleotide: Potential Mechanism of Action
Henry, S. P., Giclas, P. C., Leeds, J., Pangburn, M. K., Auletta, C. S., Levin, A. A., & Kornbrust, D. J. (1997) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)36667-4 · Cited by 204 · see citing works
Mipomersen, an apolipoprotein B synthesis inhibitor, lowers low-density lipoprotein cholesterol in high-risk statin-intolerant patients: a randomized, double-blind, placebo-controlled trial
Visser, M. E., Wagener, G., Baker, B. F., Geary, R. S., Donovan, J. M., Beuers, U. H., Nederveen, A. J., Verheij, J., Trip, M. D., Basart, D. C. G., et al. (2012) · European Heart Journal · doi:10.1093/eurheartj/ehs023 · Cited by 191 · see citing works
Absence of efficacy of subcutaneous antisense ICAM-1 treatment of chronic active Crohn's disease
Schreiber, S., Nikolaus, S., Malchow, H., Kruis, W., Lochs, H. H., Raedler, A., Hahn, E. G., Krummenerl, T., & Steinmann, G. G. (2001) · Gastroenterology · doi:10.1053/gast.2001.24015 · Cited by 186 · see citing works
Induction of Systemic TH1-Like Innate Immunity in Normal Volunteers Following Subcutaneous but Not Intravenous Administration of CPG 7909, a Synthetic B-Class CpG Oligodeoxynucleotide TLR9 Agonist
Krieg, A. Μ., Efler, S. M., Wittpoth, M., Adhami, M. J. A., & Davis, H. L. (2004) · Journal of Immunotherapy · doi:10.1097/00002371-200411000-00006 · Cited by 183 · see citing works
Effect of Mipomersen, an Apolipoprotein B Synthesis Inhibitor, on Low-Density Lipoprotein Cholesterol in Patients With Familial Hypercholesterolemia
Akdim, F., Visser, M. E., Tribble, D. L., Baker, B. F., Stroes, E. S. G., Yu, R. Z., Flaim, J., Su, J. Q., Stein, E. A., & Kastelein, J. J. P. (2010) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2010.01.003 · Cited by 178 · see citing works
Efficacy and Safety of Mipomersen, an Antisense Inhibitor of Apolipoprotein B, in Hypercholesterolemic Subjects Receiving Stable Statin Therapy
Akdim, F., Stroes, E. S. G., Sijbrands, E. J. G., Tribble, D. L., Trip, M. D., Jukema, J. W., Flaim, J., Su, J. Q., Yu, R. Z., Baker, B. F., et al. (2010) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2009.11.069 · Cited by 162 · see citing works
Complement activation is responsible for acute toxicities in rhesus monkeys treated with a phosphorothioate oligodeoxynucleotide
Henry, S. P., Beattie, G., Yeh, G., Chappel, A., Giclas, P. C., Mortari, A., Jagels, M. A., Kornbrust, D. J., & Levin, A. A. (2002) · International Immunopharmacology · doi:10.1016/s1567-5769(02)00142-x · Cited by 151 · see citing works
Oligonucleotide Conjugates for Therapeutic Applications
Winkler, J. (2013) · Therapeutic Delivery · doi:10.4155/tde.13.47 · Cited by 149 · see citing works
Long-term efficacy and safety of mipomersen in patients with familial hypercholesterolaemia: 2-year interim results of an open-label extension
Santos, R. D., Duell, P. B., East, C. A., Guyton, J. R., Moriarty, P. M., Chin, W., & Mittleman, R. S. (2013) · European Heart Journal · doi:10.1093/eurheartj/eht549 · Cited by 144 · see citing works
Postinflammatory Hyperpigmentation
Taylor, S. C., Grimes, P. E., Lim, J., Im, S., & Lui, H. (2009) · Journal of Cutaneous Medicine and Surgery · doi:10.2310/7750.2009.08077 · Cited by 137 · see citing works
Antisense and siRNA as agonists of Toll-like receptors
Agrawal, S., & Kandimalla, E. R. (2004) · Nature Biotechnology · doi:10.1038/nbt1042 · Cited by 131 · see citing works
Synthetic RNAi triggers and their use in chronic hepatitis B therapies with curative intent
Gish, R. G., Yuen, M., Chan, H. L., Given, B. D., Lai, C., LOCARNINI, S. A., Lau, J. Y. N., Wooddell, C. I., Schluep, T., & Lewis, D. L. (2015) · Antiviral Research · doi:10.1016/j.antiviral.2015.06.019 · Cited by 130 · see citing works
A phase III randomized study of gemcitabine and cisplatin with or without PF-3512676 (TLR9 agonist) as first-line treatment of advanced non-small-cell lung cancer
Manegold, C., van Zandwijk, N., Szczęsna, A., Zatloukal, P., Au, J. S. K., Błasińska-Morawiec, M., Serwatowski, P., Krzakowski, M. J., Jassem, J., Tan, E. H., et al. (2011) · Annals of Oncology · doi:10.1093/annonc/mdr030 · Cited by 128 · see citing works
Efficacy of apolipoprotein B synthesis inhibition in subjects with mild-to-moderate hyperlipidaemia
Akdim, F., Tribble, D. L., Flaim, J., Yu, R. Z., Su, J. Q., Geary, R. S., Baker, B. F., Fuhr, R., Wedel, M. K., & Kastelein, J. J. P. (2011) · European Heart Journal · doi:10.1093/eurheartj/ehr148 · Cited by 125 · see citing works
Immune stimulation--a class effect of phosphorothioate oligodeoxynucleotides in rodents.
Monteith, D. K. B., Henry, S. P., Rb, H., et al. (1997) · PubMed · Cited by 124 · see citing works
CpG motif‐independent activation of TLR9 upon endosomal translocation of “natural” phosphodiester DNA
Yasuda, K., Rutz, M., Schlatter, B., Metzger, J., Luppa, P. B., Schmitz, F., Haas, T. L., Heit, A., Bauer, S., & Wagner, H. (2006) · European Journal of Immunology · doi:10.1002/eji.200535210 · Cited by 120 · see citing works
Phase I Trial of ISIS 104838, a 2′-Methoxyethyl Modified Antisense Oligonucleotide Targeting Tumor Necrosis Factor-α
Sewell, K. L., Geary, R. S., Baker, B. F., Glover, J., Mant, T., Yu, R. Z., Tami, J. A., & Dorr, F. A. (2002) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.102.036749 · Cited by 120 · see citing works
Phase I trial of a Toll-like receptor 9 agonist, PF-3512676 (CPG 7909), in patients with treatment-refractory, cutaneous T-cell lymphoma
Kim, Y. H., Girardi, M., Duvic, M. A., Kuzel, T. M., Link, B. K., Pinter‐Brown, L. C., & Rook, A. H. (2010) · Journal of the American Academy of Dermatology · doi:10.1016/j.jaad.2009.12.052 · Cited by 115 · see citing works
Phase 1B, randomized, double-blind, dose-escalation trial of CPG 10101 in patients with chronic hepatitis C virus
McHutchison, J. G., Bacon, B. R., Gordon, S. C., Lawitz, E., Shiffman, M., Afdhal, N. H., Jacobson, I. M., Muir, A. J., Al-Adhami, M., Morris, M. L., et al. (2007) · Hepatology · doi:10.1002/hep.21773 · Cited by 114 · see citing works
Effect of apolipoprotein-B synthesis inhibition on liver triglyceride content in patients with familial hypercholesterolemia
Visser, M. E., Akdim, F., Tribble, D. L., Nederveen, A. J., Kwoh, T. J., Kastelein, J. J. P., Trip, M. D., & Stroes, E. S. G. (2009) · Journal of Lipid Research · doi:10.1194/jlr.m002915 · Cited by 112 · see citing works
Functional Comparison of Innate Immune Signaling Pathways in Primates
Barreiro, L. B., Marioni, J. C., Blekhman, R., Stephens, M., & Gilad, Y. (2010) · PLoS Genetics · doi:10.1371/journal.pgen.1001249 · Cited by 103 · see citing works
Sulfone therapy in the treatment of leukocytoclastic vasculitis
Fredenberg, M. F., & Malkinson, F. D. (1987) · Journal of the American Academy of Dermatology · doi:10.1016/s0190-9622(87)70100-5 · Cited by 94 · see citing works
Non-CpG-Containing Antisense 2′-Methoxyethyl Oligonucleotides Activate a Proinflammatory Response Independent of Toll-Like Receptor 9 or Myeloid Differentiation Factor 88
Senn, J. J., Burel, S. A., & Henry, S. P. (2005) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.105.084004 · Cited by 88 · see citing works
Phase I clinical trial of CpG oligonucleotide 7909 (PF-03512676) in patients with previously treated chronic lymphocytic leukemia
Zent, C. S., Smith, B. J., Ballas, Z. K., et al. (2011) · Leukemia & lymphoma/Leukemia and lymphoma · doi:10.3109/10428194.2011.608451 · Cited by 86 · see citing works
Drug‐elicited systemic allergic (contact) dermatitis – update and possible pathomechanisms
Thyssen, J. P., & Maibach, H. I. (2008) · Contact Dermatitis · doi:10.1111/j.1600-0536.2008.01367.x · Cited by 82 · see citing works
Preclinical Evaluation of the Toxicological Effects of a Novel Constrained Ethyl Modified Antisense Compound Targeting Signal Transducer and Activator of Transcription 3 in Mice and Cynomolgus Monkeys
Burel, S. A., Han, S.-R., Lee, H.-S., Norris, D. A., Lee, B., Machemer, T., Park, S., Zhou, T., He, G., Kim, Y., et al. (2013) · Nucleic Acid Therapeutics · doi:10.1089/nat.2013.0422 · Cited by 77 · see citing works
Fingerprinting the Substrate Specificity of M1 and M17 Aminopeptidases of Human Malaria, Plasmodium falciparum
Poręba, M., McGowan, S., Skinner-Adams, T., Trenholme, K., Gardiner, D. L., Whisstock, J., To, J., Salvesen, G., Dalton, J., & Drąg, M. (2012) · PLoS ONE · doi:10.1371/journal.pone.0031938 · Cited by 76 · see citing works
Drug-induced cutaneous pathology
Ramdial, P. K., & Naidoo, D. K. (2009) · Journal of Clinical Pathology · doi:10.1136/jcp.2008.058289 · Cited by 76 · see citing works
A phase I trial of an antisense inhibitor of hepatitis C virus (ISIS 14803), administered to chronic hepatitis C patients
McHutchison, J. G., Patel, K., Pockros, P. J., et al. (2005) · Journal of Hepatology · doi:10.1016/j.jhep.2005.09.009 · Cited by 75 · see citing works
A phase I clinical trial of a ribozyme-based angiogenesis inhibitor targeting vascular endothelial growth factor receptor-1 for patients with refractory solid tumors
Weng, D. E., Masci, P., Radka, S. F., et al. (2005) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-04-0210 · Cited by 75 · see citing works
Pharmacokinetics and safety of single doses of drisapersen in non-ambulant subjects with Duchenne muscular dystrophy: Results of a double-blind randomized clinical trial
Flanigan, K. M., Voït, T., Rosales, X. Q., et al. (2013) · Neuromuscular Disorders · doi:10.1016/j.nmd.2013.09.004 · Cited by 73 · see citing works
Targeted nanoparticle delivery overcomes off-target immunostimulatory effects of oligonucleotides and improves therapeutic efficacy in chronic lymphocytic leukemia
Yu, B., Mao, Y., Bai, L., Herman, S. E. M., Wang, X., Ramanunni, A., Jin, Y., Mo, X. M., Cheney, C. M., Chan, K. K., et al. (2012) · Blood · doi:10.1182/blood-2012-01-407742 · Cited by 65 · see citing works
Toll-Like Receptors (TLRs) and Innate Immunity
Bauer, S., & Hartmann, G. (2007) · Handbook of experimental pharmacology · doi:10.1007/978-3-540-72167-3 · Cited by 64 · see citing works
Synthetic Oligonucleotides: The Development of Antisense Therapeutics
Monteith, D. K. B., & Levin, A. A. (1999) · Toxicologic Pathology · doi:10.1177/019262339902700103 · Cited by 63 · see citing works
Oligodeoxynucleotide Studies in Primates: Antisense and Immune Stimulatory Indications
Farman, C. A., & Kornbrust, D. J. (2003) · Toxicologic Pathology · doi:10.1080/01926230390174995 · Cited by 61 · see citing works
58 FINAL RESULTS – RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED SAFETY, ANTI-VIRAL PROOF-OF-CONCEPT STUDY OF MIRAVIRSEN, AN OLIGONUCLEOTIDE TARGETING MIR-122, IN TREATMENT-NAIVE PATIENTS WITH GENOTYPE 1 CHRONIC HCV INFECTION
Reesink, H. W., Janssen, H. L. A., Zeuzem, S., Lawitz, E., Rodriguez‐Torres, M., Patel, K., Chen, A., Davis, C., King, B., Levin, A., et al. (2012) · Journal of Hepatology · doi:10.1016/s0168-8278(12)60072-5 · Cited by 60 · see citing works
Preclinical Safety Evaluation of Biopharmaceuticals
(2007) · Wiley eBooks · doi:10.1002/9780470292549 · Cited by 59 · see citing works
CD49d antisense drug ATL1102 reduces disease activity in patients with relapsing-remitting MS
Limmroth, V., Barkhof, F., Desem, N., Diamond, M. P., Tachas, G., & For the ATL1102 Study Group (2014) · Neurology · doi:10.1212/wnl.0000000000000926 · Cited by 54 · see citing works
From A to Z on CpG
Krieg, A. Μ. (2002) · Trends in Immunology · doi:10.1016/s1471-4906(01)02150-0 · Cited by 51 · see citing works
Safety and Efficacy of PF-3512676 for the Treatment of Stage IV Renal Cell Carcinoma: An Open-Label, Multicenter Phase I/II Study
Thompson, J. A., Kuzel, T. M., Drucker, B. J., et al. (2009) · Clinical Genitourinary Cancer · doi:10.3816/cgc.2009.n.025 · Cited by 51 · see citing works
Lack of Pharmacokinetic Interaction for ISIS 113715, a 2???-0-Methoxyethyl Modified Antisense Oligonucleotide Targeting Protein Tyrosine Phosphatase 1B Messenger RNA, with Oral Antidiabetic Compounds Metformin, Glipizide or Rosiglitazone
Geary, R. S., Bradley, J. D., Watanabe, T. A., et al. (2006) · Clinical Pharmacokinetics · doi:10.2165/00003088-200645080-00003 · Cited by 50 · see citing works
ISIS-FXIRx, A Novel and Specific Antisense Inhibitor of Factor XI, Caused Significant Reduction in FXI Antigen and Activity and Increased aPTT without Causing Bleeding in Healthy Volunteers
Liu, Q., Bethune, C., Dessouki, E., et al. (2011) · Blood · doi:10.1182/blood.v118.21.209.209 · Cited by 45 · see citing works
Structure Activity Relationships of α-L-LNA Modified Phosphorothioate Gapmer Antisense Oligonucleotides in Animals
Seth, P. P., Jazayeri, A., Yu, J., Allerson, C. R., Bhat, B., & Swayze, E. E. (2012) · Molecular Therapy — Nucleic Acids · doi:10.1038/mtna.2012.34 · Cited by 44 · see citing works
Safety, Pharmacokinetics and Immune Effects in Normal Volunteers of CPG 10101 (ACTILON™), an Investigational Synthetic Toll-like Receptor 9 Agonist
Vicari, A. P., Schmalbach, T., Lekstrom-Himes, J. A., et al. (2007) · Antiviral Therapy · doi:10.1177/135965350701200501 · Cited by 43 · see citing works
First proof of pharmacology in humans of a novel glucagon receptor antisense drug
van Dongen, M. G. J., Geerts, B. F., Morgan, E. S., Brandt, T. A., de Kam, M. L., Romijn, J. A., Cohen, A. F., Bhanot, S., & Burggraaf, J. (2014) · The Journal of Clinical Pharmacology · doi:10.1002/jcph.396 · Cited by 41 · see citing works
Self-citation
Toxicologic Properties of 2-O-Methoxyethyl Chimeric Antisense Inhibitors in Animals and Man
Henry, S. P., Kim, T., Kramer-Stickland, K., Zanardi, T. A., Fey, R. A., & Levin, A. A. (2007) · CRC Press eBooks · doi:10.1201/9780849387951-20 · Cited by 37 · see citing works
CpG-ODNs induces up-regulated expression of chemokine CCL9 in mouse macrophages and microglia
Ravindran, C., Cheng, Y., & Liang, S. (2009) · Cellular Immunology · doi:10.1016/j.cellimm.2009.10.001 · Cited by 36 · see citing works
Complement System in Dermatological Diseases – Fire Under the Skin
Palianus, J., & Meri, S. (2015) · Frontiers in Medicine · doi:10.3389/fmed.2015.00003 · Cited by 32 · see citing works
Oligodeoxynucleotide Studies in Primates: Antisense and Immune Stimulatory Indications
Farman, C. A., & Kornbrust, D. J. (2003) · Toxicologic Pathology · doi:10.1080/01926230309779 · Cited by 30 · see citing works
Unique O-Methoxyethyl Ribose-DNA Chimeric Oligonucleotide Induces an Atypical Melanoma Differentiation-Associated Gene 5-Dependent Induction of Type I Interferon Response
Burel, S. A., Machemer, T., Ragone, F. L., Kato, H., Cauntay, P., Greenlee, S., Salim, A., Gaarde, W. A., Hung, G., Peralta, R. Q., et al. (2012) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.112.193789 · Cited by 29 · see citing works
Changes in Mipomersen Dosing Regimen Provide Similar Exposure With Improved Tolerability in Randomized Placebo‐Controlled Study of Healthy Volunteers
Flaim, J., Grundy, J. S., Baker, B. F., McGowan, M. P., & Kastelein, J. J. P. (2014) · Journal of the American Heart Association · doi:10.1161/jaha.113.000560 · Cited by 29 · see citing works
Toxicological evaluation of oligonucleotide therapeutics.
Marquis, J. K., & Grindel, J. M. (2000) · PubMed · Cited by 25 · see citing works
Mipomersen as a potential adjunctive therapy for hypercholesterolemia
Patel, N. S., & Hegele, R. A. (2010) · Expert Opinion on Pharmacotherapy · doi:10.1517/14656566.2010.512006 · Cited by 19 · see citing works
An Overview of the Clinical Safety Experience of First- and Second-Generation Antisense Oligonucleotides
Kwoh, T. J. (2007) · CRC Press eBooks · doi:10.1201/9780849387951-21 · Cited by 19 · see citing works
Synthesis and immunological activities of novel Toll-like receptor 7 and 8 agonists
Kandimalla, E. R., Struthers, M. D., Bett, A. J., et al. (2011) · Cellular Immunology · doi:10.1016/j.cellimm.2011.03.027 · Cited by 18 · see citing works
Predictivity of animal studies for human injection site reactions with parenteral drug products
Engelhardt, J. A. (2008) · Experimental and Toxicologic Pathology · doi:10.1016/j.etp.2008.04.003 · Cited by 17 · see citing works
Local and systemic activationofthe whole complement cascade in human leukocytoclastic cutaneous vasculitis; C3d,g and terminal complement complex as sensitive markers
Dauchel, H., Joly, P., DELPECH, A., et al. (1993) · Clinical & Experimental Immunology · doi:10.1111/j.1365-2249.1993.tb03392.x · Cited by 16 · see citing works
Preclinical Studies on Intestinal Administration of Antisense Oligonucleotides as a Model for Oral Delivery for Treatment of Duchenne Muscular Dystrophy
van Putten, M., Young, C. S., van den Berg, S. A. A., et al. (2014) · Molecular Therapy — Nucleic Acids · doi:10.1038/mtna.2014.62 · Cited by 16 · see citing works
Stimulation of the Immune System by Therapeutic Antisense Oligodeoxynucleotides and Small Interfering RNAs via Nucleic Acid Receptors
Richardt‐Pargmann, D., & Vollmer, J. (2009) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2009.04971.x · Cited by 13 · see citing works
Newly identified CpG ODNs, M5-30 and M6-395, stimulate mouse immune cells to secrete TNF-α and enhance Th1-mediated immunity
Choi, S.-S., Chung, E., & Jung, Y. (2010) · The Journal of Microbiology · doi:10.1007/s12275-010-0053-6 · Cited by 13 · see citing works
Apolipoprotein B Synthesis Inhibition by Mipomersen Reduces LDL-C When Added to Maximally Tolerated Lipid-Lowering Medication in Patients with Severe Heterozygous Hypercholesterolemia †
Tardif, J., Češka, R., Burgess, L. J., et al. (2011) · Journal of clinical lipidology · doi:10.1016/j.jacl.2011.03.040 · Cited by 12 · see citing works
EFFECT OF MIPOMERSEN ON LIPOPROTEIN(A) IN PATIENTS WITH HYPERCHOLESTEROLEMIA ACROSS FOUR PHASE III STUDIES
Tsimikas, S., Witztum, J. L., & Catapano, A. L. (2012) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(12)61495-8 · Cited by 11 · see citing works
Circulating immune complexes in cynomolgus macaques.
Alexander, N. J., Clarkson, T. B., & Fulgham, D. L. (1985) · PubMed · Cited by 9 · see citing works
A phase I study of HYB2055 in patients (pts) with advanced solid malignancies
Hwang, J. J., Park, S., Amin, A., et al. (2004) · Journal of Clinical Oncology · doi:10.1200/jco.2004.22.90140.3111 · Cited by 7 · see citing works
Long Term Efficacy and Safety of Mipomersen During 4 Years of Treatment in a Cohort of Patients with Heterozygous Familial Hypercholesterolemia and Coronary Artery Disease (CAD)
Duell, P. B., Rose, J., Selvey, S., et al. (2013) · Journal of clinical lipidology · doi:10.1016/j.jacl.2013.03.080 · Cited by 6 · see citing works
Technology evaluation: HYB-2055, Hybridon.
Świtaj, T., & Lasek, W. (2005) · PubMed · Cited by 6 · see citing works
Safety and Efficacy of Mipomersen Administered as Add-on Therapy in Patients with Hypercholesterolemia and High Cardiovascular Risk†
Cromwell, W. C., Thomas, G. S., Boltje, I., et al. (2012) · Journal of clinical lipidology · doi:10.1016/j.jacl.2012.04.072 · Cited by 5 · see citing works
A phase I study of HYB2055 in patients (pts) with advanced solid malignancies
Hwang, J. J., Park, S., Amin, A., et al. (2004) · Journal of Clinical Oncology · doi:10.1200/jco.2004.22.14_suppl.3111 · Cited by 5 · see citing works
Mipomersen, a First-in-Class Apolipoprotein B Synthesis Inhibitor, Lowers Lipoprotein (a) in Patients with Homozygous Familial Hypercholesterolemia
Cromwell, W. C., Santos, R. D., Blom, D. J., et al. (2010) · Journal of clinical lipidology · doi:10.1016/j.jacl.2010.03.055 · Cited by 3 · see citing works
G.P.113
Goemans, N., Tulinius, M., Wilson, R., et al. (2014) · Neuromuscular Disorders · doi:10.1016/j.nmd.2014.06.127 · Cited by 2 · see citing works
Mipomersen, an Apolipoprotein B Synthesis Inhibitor, Reduces LDL-C in HoFH Pediatric Patients†
Selvey, S., & Raal, F. J. (2014) · Journal of clinical lipidology · doi:10.1016/j.jacl.2014.02.056 · Cited by 2 · see citing works

Flagged first, then by citations

Research works printed but not linked: 7

Genzyme Corporation. KYNAMRO: Highlights of prescribing information. Cambridge, MA: Genzyme Corporation, 2013.
Agrawal S, Kandimalla ER. Role of Toll-like receptors in antisense and siRNA [corrected]. Nat Biotechnol 2004; 22: 1533-7.
Goemans N, Voit T, McDonald C, Watson C, Kraus J, Rolfe K, et al. Drisapersen treatment for Duchenne muscular dystrophy: results of a 96-week follow-up of an open-label extension study following two placebo-controlled trials. Neurology 2014; 83: e34-40.
Goemans N, Tulinius M, Wilson R, Wardell C, Bedwell P, Campion G. G.P.113: Drisapersen (DRIS) treatment for Duchenne muscular dystrophy (DMD): results of up to 188 weeksGÇÖ follow-up of an open-label extension study. Neuromuscul Disord 2014; 24: 829.
McHutchison JG, Bacon BR, Gordon SC, Afdhal NH, Jacobson IM, Muir A, et al. Human pharmacologic activity of a new TLR9 agonist antiviral, CPG 10101 (ACTILON). Hepatology 2004; 40: 697A.
Viney N, Hughes SG, Singleton W, Crooke RM, Graham MJ, Su J, et al. ISIS APO (a) Rx, an antisense inhibitor to apolipoprotein (a), reduces plasma levels of Lp (a) and oxidized phospholipids/apoB-100 in healthy volunteers. Eur Heart J 2014; Conference: European Society of Cardiology: 01 Sep 2014. 100
Brandt TA, Crooke ST, Ackermann EJ, Xia S, Morgan ES, Liu Q, et al. Isis 113715, a novel PTP-1B antisense inhibitor, improves glycemic control and dyslipidemia and increases adiponectin levels in T2DM subjects uncontrolled on stable sulfonylurea therapy. Diabetes 2010; ; Conference: 70th Scientific Sessions of the American Diabetes Association Orlando: 2010. 102 PRNewswire. ATL1103 Phase II Trial -Successful Efficacy Results, 2 September 2014. 103 Isis Pharmaceuticals, Inc. Isis Pharmaceuticals Reports Final Phase 2 Data on ISIS-GCGR RX, Press release, 16 June 2014.

Sorted by citations

Lymph-node-targeted, mKRAS-specific amphiphile vaccine in pancreatic and colorectal cancer: the phase 1 AMPLIFY-201 trial
Pant, S., Wainberg, Z. A., Weekes, C. D., Furqan, M., Kasi, P. M., Devoe, C. E., Leal, A. D., Chung, V., Basturk, O., VanWyk, H., et al. (2024) · Nature Medicine · doi:10.1038/s41591-023-02760-3 · Cited by 267 · see citing works
Effect of Vupanorsen on Non–High-Density Lipoprotein Cholesterol Levels in Statin-Treated Patients With Elevated Cholesterol: TRANSLATE-TIMI 70
Bergmark, B. A., Marston, N. A., Bramson, C. R., Curto, M., Ramos, V., Jevne, A., Kuder, J. F., Park, J.-G., Murphy, S. A., Verma, S., et al. (2022) · Circulation · doi:10.1161/circulationaha.122.059266 · Cited by 216 · see citing works

Authors: van Meer, L., Moerland, M., Gallagher, J., van Doorn, M. B. A., Prens, E. P., Cohen, A. F., Rissmann, R., & Burggraaf, J.
Affiliations: Centre for Human Drug Research Leiden the Netherlands
Centre for Human Drug Research (NL)
Department of Dermatology Erasmus MC University Medical Center Rotterdam
Erasmus MC (NL)
ORCID: Moerland, Matthijs
Prens, Errol P.
Cohen, Adam F.
Rissmann, Robert
Burggraaf, Jacobus
Venue: British Journal of Clinical Pharmacology
Publisher: Wiley
Published: 2016-05-31
Volume: 82
Issue: 2
Pages: 340-351
ISSN: 0306-5251 (ISSN-L)
1365-2125
DOI: 10.1111/bcp.12961
PMC: PMC4972150
OpenAlex: W2338194364
Cited by: 45
References: 95
Citations by year: 2026: 5 · 2025: 5 · 2024: 5 · 2023: 3 · 2022: 4 · 2021: 1 · 2020: 3 · 2019: 8 · 2018: 4 · 2017: 5 · 2016: 2
FWCI: 1.44
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: public-domain
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: British Journal of Clinical Pharmacology (publishedVersion, public-domain)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
RePub (Erasmus University Rotterdam) (submittedVersion)
Topics: Health Sciences › Medicine › Emergency Medicine › Intramuscular injections and effects
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
Life Sciences › Immunology and Microbiology › Immunology › Biosimilars and Bioanalytical Methods
Keywords: injection site reactions, oligonucleotide therapeutics, subcutaneous administration, erythema, skin ulcers, necrosis, immunostimulatory properties, incidence of adverse reactions
MeSH terms: Drug Eruptions, Dose-Response Relationship, Drug, Humans, Injections, Subcutaneous, Oligonucleotides, Severity of Illness Index, Incidence

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Injection site reactions after subcutaneous oligonucleotide therapy

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Self-check

Cites

Cited by

Related

Record

About these checks