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COPENHAGEN -- Long-term treatment with serial of urinary incontinence among multiple sclerosis (MS) patients appeared to be safe and effective, researchers reported here.
Daily urinary incontinence episodes due to neurogenic detrusor overactivity dropped dramatically with the 200-unit dose of onabotulinum toxin A from 4.8 episodes a day to an average of about one a day, said, from the in London, and colleagues.
Action Points
- Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
That reduction was consistent up to five cycles of treatment, he added during a presentation at the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) annual meeting.
Panicker said that while a higher dose (300 units) of onabotulinum A showed virtually the same results, the had a better adverse event profile and is approved as the clinical dose.
He said that the higher onabotulinum toxin A showed no additional clinically meaningful benefits, and was associated with more urinary retention and uncomplicated urinary tract infections.
"This is the first, large, multicenter, prospective long-term trial to demonstrate consistent efficacy and tolerability of repeat onabotulinum toxin A treatment in MS patients," the group wrote.
The current research was based on a 3-year, open-label extension study of a phase III trial of onabotulinum toxin A treatment in MS patients with urinary incontinence due to neurogenic detrusor overactivity. The treatment involved up to 30 injections of onabotulinum toxin A into the wall of the bladder, with special attention to avoiding the trigone, he said.
The research team assigned 119 patients to treatment with 200 units of onabotulinum toxin A and 111 patients to the 300-unit dose.
The average age of the study population was 50 and women made up more than three-fourths of patients. They had been diagnosed with neurogenic detrusor overactivity and about half of the participants had previously been treated with anticholinergic drugs. At baseline, 45 of the patients in the 200-unit dose group were using catheters as were 32 in the higher dose group.
Also at baseline, there was an average of 4.8 urinary incontinence episodes per day in the 200-unit group and 4.6 in the 300-unit group.
At week 6, mean reduction in episodes per day ranged from about 3.6 to 4.3 for the 200-unit group and about 3.8 to 4.7 per day for the 300-unit group across treatment cycles one to five, resulting in an average of only one episode per day (range 0.3-1.1), the group reported.
Annualized MS exacerbation rates ranged from 0.06-0.22 across both dose groups for all cycles.
The most common major adverse event following treatment was urinary retention. Panicker said that 29.6% of the patients who had not required catheterization prior to treatment with the 200-unit dose initiated catheter use after the first cycle of treatment. If patients tolerated treatment in the first cycle, the catheterization requirement was greatly reduced in the second (4.3% of patients) and third cycles (6.1%).
The need for initial catheterization due to urinary retention was greater in the 300-unit group, with 44.9% requiring initial catheterization to relieve fluid retention. That dropped to 17.1% after the second treatment cycle and to 4.8 % after the third cycle.
The need for catheterization in both groups was "worrisome," said Vesna Brinar, MD, PhD, from in Croatia.
"I would be very careful in offering this treatment to my patients," Brinar told 鶹ý. "I am concerned about the high rate of urinary retention that was seen in both doses of onabotulinum A treatment."
"[Catheterization] is very uncomfortable and inconvenient for patients," added Brinar, who moderated the ECTRIMS session where the results were presented. "I think this treatment might be offered to a very carefully selected patient population."
Panicker said about 64% of the original cohort were still on treatment at the time of his presentation. While 79 patients dropped out of the study, just 10 of them quit because of adverse events or lack of efficacy. "During the extension phase of this study, no new safety signals were observed with repeat onabotulinum toxin A treatment," he added.
Disclosures
The trial was sponsored by Allergan.
Panicker disclosed commercial relationships with Allergan, Astellas, AstraTech, and FirstKind. Co-authors also disclosed commercial relationships AMS, Astellas, Hollister, Medtronic, Watson, Coloplast, Contura, NovaBay, Wellspect and Sigma Tau. Other co-authors are employees of Allergan.
Brinar reported no conflicts of interest.
Primary Source
European Committee for Treatment and Research in Multiple Sclerosis
Source Reference: Panicker J, et al "Consistent long-term efficacy of onabotulinumtoxinA in patients with neurogenic detrusor overactivity due to multiple sclerosis: an interim analysis after five treatment cycles" ECTRIMS 2013; Abstract 168.