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INTRODUCTION: Cervical dystonia (CD) is a neurologic movement disorder with potentially disabling effects and significant impact on quality of life of those affected. AbobotulinumtoxinA (aboBoNT-A) was initially approved for a dilution of 500 U/1 mL and subsequently for a dilution of 500 U/2 mL, providing flexibility for clinicians to treat CD. Here, we explore the safety and efficacy of the 500 U/2 mL dilution versus 500 U/1 mL dilution of aboBoNT-A in a retrospective analysis based on published clinical trial data. METHODS: The safety and efficacy of aboBoNT-A in patients with CD was evaluated in three multicenter, double-blind, randomized, placebo-controlled trials and open-label extensions. Trials 1 (NCT00257660) and 2 (NCT00288509) evaluated the 500 U/1 mL dilution in 80 and 116 patients, respectively; Trial 3 (NCT01753310) evaluated the 500 U/2 mL dilution in 125 patients. RESULTS: Comparison of the adjusted mean difference in TWSTRS total scores at Week 4 from baseline for aboBoNT-A in Trial 1 (-6.0; 95% CI, -10.8, -1.3), Trial 2 (-8.8; 95% CI, -12.9, -4.7), and Trial 3 (-8.7; 95% CI, -13.2, -4.2) showed similar, significant improvements. Dysphagia and muscle weakness patterns were comparable across the three trials, indicating that an increased dilution of aboBoNT-A does not result in an increased risk of diffusion-related adverse events. CONCLUSION: The results of these trials show that aboBoNT-A is similarly efficacious using either dilution, with similar safety and tolerability across trials. Having the 500 U/1 mL and 500 U/2 mL dilution volumes available provides further flexibility in administration, benefiting patient care.
RESUMEN
Oligonucleotides induce various cellular responses which are not due to the blockade of protein synthesis by an antisense mechanism. Oligonucleotides presenting double-stranded or G-quartet structures (ribo- or deoxyribonucleotides, phosphodiester or phosphorothioated) induce retraction of neurites and aggregation of chicken retinal cells within 10-20 h. This effect is reversible, non-toxic; it appears to require internalization and can be mimicked by treatment of the cells with an RGDS peptide. The oligonucleotides appear to trigger a cascade of intracellular events, affecting the adhesive properties of integrins. In addition, a subset of oligonucleotides induced platelet aggregation, probably through their interaction with membrane receptors. Recognition of these effects is important for the design and interpretation of antisense experiments.