VANCOUVER, BC—Arbaclofen extended-release tablets (AERT) proved greater tolerability, and similar efficacy and safety, to baclofen in patients with multiple sclerosis (MS), according to randomized trial results reported at the 68th AAN Annual Meeting.
“AERT administered twice a day was efficacious, safe, and well tolerated in MS patients with spasticity,” reported Daniel Kantor, MD, of the Neurologique Foundation, Inc., Ponte Vedra, FL.
Baclofen, a gamma-aminobutyric acid-b (GABA-b) receptor agonist, is the current treatment standard for spasticity in MS. However, it can cause central nervous system side effects such as drowsiness, leading to decreased adherence and tolerability.
Dr. Kantor and colleagues hypothesized that treatment with AERT can reduce dosing frequency and, in turn, adverse events.
The study compared 3 different doses of AERT (20, 30, and 40mg/day), with baclofen tablets, USP (40, 60, and 80mg/day) with matching placebo.
“Low and medium doses were given over a 2-week period for each dose, following by a 12-week maintenance period on the higher dose,” they explained. Co-primary endpoints were efficacy, assessed using the Total Numeric Transformed Modified Ashworth Scale (TNmAS) in the most affected limb, and the Clinician Global Impression of Change (CGIC) at the end of the maintenance period.
A total of 354 patients were randomly assigned to AERT (n=114), baclofen (n=118), and placebo (n=122). Mean age was 44.2 years; 59% were women and 95.8% were white. Mean duration of MS was 9.93 years and mean duration of spasticity, 6.37 years. Among the patients, 59.0% had relapsing remitting MS, 36.7% had secondary progressive MS, and 2.8% had primary progressive MS.
Results showed that at the end of the maintenance period, Day 120, the average decrease in TNmAS score was larger in the AERT group, -2.85, compared with placebo, -1.90. This suggests “significant improvement in tone for the AERT subjects compared to placebo subjects (P=0.0004),” Dr. Kantor noted.
“The changes in TNmAS of the most affected limb from baseline were significantly higher than placebo in all visits, including the first 4 weeks of treatment with lower doses, 20 and 30mg/day,” he added.
As shown on the CGIC, a larger improvement in the overall clinical subject status was observed with AERT (0.98) compared with placebo (0.50; P=0.0003). Starting at Day 36, changes in CGIC from baseline were significantly higher in the AERT group, but not in the baclofen group, compared to placebo.
As measured by TNmAS, CGIC, and the MS Spasticity Scale (MSSS-88), the efficacy of AERT was not significantly different from baclofen.
“Improvement in MSSS-88 was significantly larger for the AERT group when compared to the placebo group (P=0.02), indicating an improvement in the overall functional performance and sense of impairment with respect to the level of spasticity,” they stated.
No significant changes were found at the end of the maintenance period for any of the treatment groups on the Expanded Disability Status Scale; however, AERT “was associated with less sleepiness.”
The most commonly reported adverse events were somnolence, dizziness, asthenia, urinary tract infection, muscle weakness, and pollakiuria. “AERT was associated with less adverse events and fewer discontinuations of treatment than baclofen,” Dr. Kantor concluded.
Dr. Kantor received speaking and/or consulting fees from Osmotica.