Assessment of confirmed urinary tract infection in patients treated with dalfampridine for multiple sclerosis

Abstract

Urinary tract infections (UTIs) were reported frequently with dalfampridine extended-release (dalfampridine-ER) 10 mg relative to placebo in previous multiple sclerosis (MS) studies. The objective of this study was to determine whether dalfampridine-ER is associated with increased incidence of confirmed UTIs in MS patients. This post hoc analysis used UTI data from a study comparing the 4-week safety and efficacy of 5 mg (n = 144) and 10 mg (n = 142) twice-daily dalfampridine-ER versus placebo (n = 143). To confirm UTIs, three clinical assessments were used: standard urinalysis (leukocytes > 5/high-power field); urine culture (≥ 100,000 and ≥ 10,000 colony-forming units [CFUs]/mL) for those who reported UTIs as adverse events (AEs) or had positive urinalysis; and UTI symptomatology. Fisher’s exact test assessed statistical significance. The proportion of patients who reported UTIs as AEs in the placebo and dalfampridine-ER 5 mg and 10 mg groups were 5.6%, 6.3%, and 9.9%, respectively. In comparison, those with laboratory-confirmed UTIs were lower: ≥ 100,000 CFUs/mL: 4.2%, 2.8%, and 2.8%; and ≥ 10,000 CFUs/mL: 4.2%, 3.5%, and 4.9%, respectively (no significant statistical difference across treatments). The proportion of patients with confirmed UTI was similar between dalfampridine-ER and placebo, thus suggesting that the treatment does not increase the risk of UTIs.

Keywords :

• 4-aminopyridine
• dalfampridine
• MS relapse
• multiple sclerosis
• urinary tract infection

Acknowledgments

This work was supported by Acorda Therapeutics, Inc., Ardsley, NY, USA. Kantor, Chancellor, Henney, and Rabinowicz were involved in the concept and design of the post hoc analysis, review of data, and manuscript development. Data analysis was performed by Snell. Editorial assistance was provided by E Jay Bienen, PhD, of The Curry Rockefeller Group, LLC, Tarrytown, NY, USA, and funded by Acorda Therapeutics, Inc., Ardsley, NY, USA. Trial Registration: NCT01328379.

Declaration of interest

D Kantor has received honoraria or payments for consulting, advisory services, and speaking services from Acorda Therapeutics, Inc., Allergan, Avanir, Biogen Idec, Depomed, Genzyme, Novartis, Questcor, Osmotica, and Teva and has received research support from Acorda Therapeutics, Inc., Avanir, Biogen Idec, Genzyme, Novartis, and Teva. CW Snell and AL Rabinowicz are employees of Acorda Therapeutics, Inc., with stock options. HR Henney III was an employee of Acorda Therapeutics, Inc., at the time of the study. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

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