Daniel Kantor, MD
Spasticity is common in MS and is associated with significant morbidity. The standard treatment is oral administration of baclofen, a γ-aminobutyric acid-b (GABA-b) receptor agonist. Baclofen is a racemic mixture, and its efficacy is thought to result from the R-enantiomer (arbaclofen). Therapeutic doses of baclofen can cause CNS side effects, decreased adherence, and decreased tolerability. Arbaclofen extended-release tablets potentially could reduce dosing frequency and adverse events.
Daniel Kantor, MD, a neurologist from Coconut Creek, Florida, and colleagues conducted a multicenter, randomized, double-blind, parallel-group study to compare the efficacy and safety of arbaclofen extended-release tablets to those of placebo and baclofen over 12 weeks of treatment in patients with spasticity due to MS. Participants were randomized to receive 20 mg of arbaclofen bid, 20 mg of baclofen tablets qid, or matching placebo. The dose was titrated over four weeks, followed by a 12-week maintenance period. The primary end points were the mean changes in Total Numeric-transformed Modified Ashworth Scale (TNmAS) and Clinician Global Impression of Change (CGIC) at the end of the maintenance period.
Of 354 randomized participants, 59.0% had relapsing-remitting MS and 36.7% had secondary progressive MS. The average baseline TNmAS score was 7.78. Mean changes in TNmAS and CGIC were significantly greater for patients receiving arbaclofen, compared with patients receiving placebo. The researchers observed a greater difference in CGIC between arbaclofen and placebo, compared with that between baclofen and placebo, perhaps because of improved tolerability of arbaclofen, compared with baclofen. Differences between arbaclofen and baclofen were not statistically significant. MS Spasticity Scale (MSSS-88) showed a statistically significant improvement among patients receiving arbaclofen, compared with those receiving placebo. Epworth Sleepiness Scale (ESS) showed a statistically significant increase in sleepiness in the baclofen group, but not in the arbaclofen group, compared with placebo. Drowsiness and dizziness were less frequent in the arbaclofen group, compared with baclofen.
The study was supported by Osmotica Pharmaceutical.