Arbaclofen Extended-Release Found Safe, Reduced Spasticity in Patients With Multiple Sclerosis

Arbaclofen extended-release (ER) reduced spasticity in patients with multiple sclerosis and was found to be safe and well-tolerated, according to 2 new abstracts presented at the 33rd Annual Meeting of the Consortium of Multiple Sclerosis Centers.

“Spasticity is common in patients with MS and associated with significant morbidity. The standard treatment is oral baclofen, a γ-aminobutyric acid-b receptor agonist. Baclofen is a racemic mixture while arbaclofen is the more active R-enantiomer,” researchers said. “Therapeutic doses of baclofen may cause side effects and decreased adherence arbaclofen ER tablets allow for twice-daily administration, reducing dosing frequency, and may reduce adverse events (AEs) in some patients.”

In the first abstract,¹ researchers conducted a multicenter, double-blind, parallel group study to compare the safety and efficacy of arbaclofen to baclofen and placebo in MS patients with spasticity.

A total of 341 participants from North America and Eastern Europe were included. Of the total, 57.5% had relapsing-remitting MS, 38.4% had secondary progressive MS, 2.6% had primary progressive MS, and 0.9% had progressive relapsing MS.

Participants were randomized in a 1:1:1 ratio and received either 2 daily doses of arbaclofen ER 20 mg, 4 daily doses of baclofen 20 mg, or placebo. Dosages were titrated over 2 weeks and followed by 12 weeks of maintenance treatment.

The study’s co-primary endpoints were the mean change in Total Numeric-transformed Modified Ashworth Scale for the most affected limb (TNmAS-MAL) and Clinician Global Impression of Change (CGIC) from baseline to the maintenance period.

The mean baseline TNmAS-MAL was:

• 7.93 in the arbaclofen group
• 7.75 in the baclofen group
• 7.55 in the placebo group

At the end of the maintenance period,

• the mean TNmAS-MAL decrease was larger in the arbaclofen group than in the placebo group
• CGIC was significantly improved in the arbaclofen group compared to the placebo group
• the change in MS Spasticity Scale (MSSS-88) was higher in the arbaclofen group than in the placebo group
• arbaclofen ER was found not to be significantly different from baclofen on the TNmAS, CGIC, or MSSS-88

Participants in the arbaclofen group reported lower frequencies of drowsiness and dizziness compared to the baclofen group. Also, 63, or 57.3%, of participants in the arbaclofen group, 82, or 72.6%, in the baclofen group, and 59, or 50.0%, in the placebo group reported treatment-emergent AEs. The most common were somnolence, asthenia, and muscle weakness.

Researchers concluded that a twice daily dose of arbaclofen ER was an effective, well-tolerated treatment for MS patients with spasticity.

In the second abstract,² researchers conducted a multicenter, open-label, single-arm study to evaluate the long-term safety of arbaclofen ER over 1 year of treatment.

The study included 182 patients with MS from North America and Eastern Europe. Of the total, 27, or 14.8%, had participated in the safety and efficacy study from the first abstract, about 63% were female, and they had a mean age of 48 years. Those who hadn’t participated in the previous study were arbaclofen ER-naïve. The mean duration of spasticity was 12 years among participants in the previous study and 7 years among those who never received arbaclofen ER.

All patients were maintained on arbaclofen ER 20 mg twice daily, the highest tolerated dose, for up to a year. The dosage was gradually reduced at the conclusion of the maintenance period.

Out of all participants, 148, or 80.4%, reported treatment-emergent AEs. Researchers found:

• 24 participants, or 13.0%, reported muscle weakness
• 21 participants, or 11.4%, reported a urinary tract infection
• 18 participants , or 9.8%, reported somnolence
• 16 participants, or 8.7%, reported dizziness
• 12 participants, or 6.5%, reported pollakiuria
• 11 participants, or 6.0%, reported asthenia

Serious AEs were reported by 15 patients who were previously arbaclofen ER-naïve and by 5 who weren’t. Delirium was the only AE considered to be possibly related to arbaclofen ER. Researchers reported that no deaths occurred during the course of the study. The TNmAS-MAL score remained consistent throughout the maintenance period.

“Arbaclofen ER administered twice daily was safe and well tolerated in patients with MS-related spasticity. A reduction in spasticity, as measured by TNmAS-MAL, was maintained throughout the treatment period,” researchers concluded.

Reference

1. Kantor D, deVries T, Dentiste A, et al. Arbaclofen extended-release tablets versus placebo or Baclofen for the treatment of spasticity in subjects with multiple sclerosis (Study OS440-3002). Presented at: 33rd Annual Meeting of the Consortium of Multiple Sclerosis Centers; May 28-June 1, 2019; Seattle, Washington. Abstract SXM07.

2. Hunter SF, deVries T, Dentiste A, et al. One-year study to evaluate the long-term safety of Arbaclofen extended-release tablets in multiple sclerosis—related spasticity (Study OS440-3003). Presented at: 33rd Annual Meeting of the Consortium of Multiple Sclerosis Centers; May 28-June 1, 2019; Seattle, Washington. Abstract SXM08.