Dataset Information

Injection site reactions after subcutaneous oligonucleotide therapy.

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.

SUBMITTER: van Meer L

PROVIDER: S-EPMC4972150 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Injection site reactions after subcutaneous oligonucleotide therapy.

van Meer Leonie L Moerland Matthijs M Gallagher Jolie J van Doorn Martijn B A MB Prens Errol P EP Cohen Adam F AF Rissmann Robert R Burggraaf Jacobus J

British journal of clinical pharmacology 20160531 2

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 exte ...[more]

PMID: 27061947

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Project description:BackgroundIn patients with relapsing-remitting multiple sclerosis (RRMS), subcutaneous (sc) interferon (IFN)β-1a and IFNβ-1b have been shown to reduce relapse rates. A formulation of IFNβ-1a has been produced without fetal bovine serum and without human serum albumin as an excipient (not currently approved for use in the US). The objectives of this study were to evaluate tolerability, injection-site redness, subject-reported satisfaction with therapy, and clinical safety and efficacy of the serum-free formulation of IFNβ-1a versus IFNβ-1b in IFNβ-treatment-naïve patients with RRMS. The objectives of the extension phase were to evaluate long-term safety and tolerability of IFNβ-1a.MethodsThis randomized, parallel-group, open-label study was conducted at 27 clinical sites in the US. Eligible patients aged 18-60 years were randomized to receive either IFNβ-1a, titrated to 44 μg sc three times weekly (tiw) (n = 65), or IFNβ-1b, titrated to 250 μg sc every other day (n = 64) over 12 weeks. Following this, all patients received IFNβ-1a 44 μg tiw for 82-112 weeks. Primary endpoint was mean change in patient-reported pain, as assessed by visual analog scale (VAS) diary pain score (from 0 mm [no pain] to 100 mm [worst possible pain]) at the injection site, from pre-injection to 30 min post-injection over the first 21 full-dose injections. Secondary assessments included proportion of patients pain-free as recorded by VAS diary and the Short-Form McGill Pain questionnaire VAS.ResultsA total of 129 patients were included in the intent-to-treat analysis. Mean (standard deviation) change in VAS diary pain score was not significantly different between groups, although numerically lower with IFNβ-1a versus IFNβ-1b from pre-injection to immediately post-injection (1.46 [2.93] vs. 4.63 [10.57] mm), 10 min post-injection (0.70 [1.89] vs. 1.89 [5.75] mm), and 30 min post-injection (0.67 [2.32] vs. 1.14 [4.94] mm). Proportion of patients pain-free at all time periods post-injection was also not significantly different between groups. Adverse events were consistent with the known safety profiles of these treatments.ConclusionsIn IFNβ-treatment-naïve patients with RRMS, both the serum-free formulation of IFNβ-1a and IFNβ-1b treatments were generally accompanied by low-level injection-site pain and were well tolerated.Trial registrationClinicalTrials.gov NCT00428584.

Dataset Information

Injection site reactions after subcutaneous oligonucleotide therapy.

Publications

Injection site reactions after subcutaneous oligonucleotide therapy.

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