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Immunostimulatory Agent Evaluation: Lymphoid Tissue Extraction and Injection Route-Dependent Dendritic Cell Activation
Published on: September 16, 2018
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Injection site reactions after subcutaneous oligonucleotide therapy
Leonie van Meer1, Matthijs Moerland1, Jolie Gallagher1
1Centre for Human Drug Research, Leiden, the Netherlands.
British Journal of Clinical Pharmacology
|April 11, 2016
Summary
Oligonucleotides (ONs) cause injection site reactions (ISRs) in 22-100% of patients. Higher doses increase ISR severity, impacting long-term use of these nucleic acid therapies.
Area of Science:
- Pharmacology
- Dermatology
- Molecular Biology
Background:
- Oligonucleotides (ONs) are nucleic acid-based therapeutics.
- Subcutaneous (sc) administration of ONs frequently causes local injection site reactions (ISRs).
- ISRs are poorly characterized in existing literature.
Purpose of the Study:
- To review the incidence and clinical features of ISRs associated with sc-administered ONs.
- To consolidate data on ISRs from literature and internal sources.
- To highlight the impact of ISRs on the clinical application of ON therapeutics.
Main Methods:
- Structured literature search for reported ISR incidence and features.
- Inclusion of institutional data on file.
- Analysis of 70 relevant manuscripts.
Main Results:
- All investigated sc-administered ONs caused ISRs.
- Incidence of ISRs ranged from 22% to 100%, with most ONs affecting over 70% of subjects.
- ISR incidence and severity correlated with higher doses, but not clearly with ON chemistry or target.
Conclusions:
- ISRs are a significant challenge for sc-administered ONs.
- Understanding ISRs is crucial for developing more clinically applicable ONs for broader patient populations.
- Further research into the immunostimulatory properties of ISRs is needed.
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