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Injection site reactions after long-term subcutaneous delivery of drisapersen: a retrospective study
- Source :
- Eur J Pediatr
- Publication Year :
- 2018
- Publisher :
- Springer Science and Business Media LLC, 2018.
-
Abstract
- A retrospective study in which we reviewed the hospital files of a subset of 7 patients with Duchenne muscular dystrophy participating in the open-label phase I/II PRO051-02 study in Leuven. The objective of this study was to describe in detail the injection site reactions in these children treated with drisapersen (PRO-051), a 2'-O-methyl phosphorothioate RNA antisense oligonucleotide, that induces exon 51 skipping in Duchenne muscular dystrophy. Antisense oligonucleotides, restoring the reading frame by skipping of exons, have become a potential treatment of Duchenne muscular dystrophy and other monogenetic diseases. Erythema followed by hyperpigmentation, fibrosis, and calcification were seen at the injection sites in all children. Ulcerations, which were difficult to heal, occurred in 5 of 7 children. Progression still occurred after switching to intravenous administration of drisapersen or even after stopping therapy. Systemic reactions included a reversible proteinuria and α1-microglobulinuria. Moreover, hypotrichosis was a common feature.Conclusion: Subcutaneous administration of drisapersen causes severe and progressive injection site effects. What is known: • Antisense oligonucleotides offer the possibility to convert Duchenne muscular dystrophy to the less severe Becker type. This can potentially be achieved by targeting and skipping specific exons of the Duchenne muscular dystrophy gene to restore the disrupted reading frame and to induce the production of a semi functional dystrophin protein. • Drisapersen is such an antisense oligonucleotides which can be administered subcutaneously. Its use has been tested extensively in the escalating dose pilot study (PRO051-02). What is new: • This report describes the injection site reactions caused by this type of agent in detail which has never been done before. We therefore reviewed the hospital files of 7 patients with Duchenne muscular dystrophy participating in the phase I/II open-label, escalating dose pilot study (PRO051-02) with drisapersen. • Severe side effects starting with erythema, hyperpigmentation, and later fibrosis, calcification, and difficult to treat ulcerations developed in all patients, and these continued to progress even after cessation of drisapersen. We discuss some possible underlying mechanisms. The exact mechanism however is still not known.
- Subjects :
- medicine.medical_specialty
Erythema
Injections, Subcutaneous
Duchenne muscular dystrophy
Oligonucleotides
Pilot Projects
Gastroenterology
Article
03 medical and health sciences
0302 clinical medicine
Fibrosis
030225 pediatrics
Internal medicine
Humans
Medicine
030212 general & internal medicine
Child
Drisapersen
Retrospective Studies
Proteinuria
business.industry
Retrospective cohort study
Oligonucleotides, Antisense
medicine.disease
Hyperpigmentation
Injection Site Reaction
Muscular Dystrophy, Duchenne
Pediatrics, Perinatology and Child Health
Hypotrichosis
medicine.symptom
business
Subjects
Details
- ISSN :
- 14321076 and 03406199
- Volume :
- 178
- Database :
- OpenAIRE
- Journal :
- European Journal of Pediatrics
- Accession number :
- edsair.doi.dedup.....0ce278de3448bae8fd25116642981bff