Oral agents promise to both increase efficacy and decrease the burden of injections in patients with MS, thus allowing earlier treatment and better long-term compliance. Although no oral agents are currently approved by the US Food and Drug Administration for use in MS, several recent studies have documented clinical and magnetic resonance imaging (MRI) activity of oral immunomodulators in RRMS. Noteworthy results presented at WCTRIMS from separate study extensions of laquinimod and fingolimod phase 2 placebo-controlled trials showed sustained benefits with these oral agents.
Persistent inhibition of clinical and MRI activity was also reported in a similarly designed 3-year extension study of oral fingolimod (FTY720) in patients with RRMS.[3] At the end of the 6-month placebo-controlled phase, the original fingolimod dose (1.25 or 5.0 mg/day) was either continued or placebo-treated patients were re-randomized to active treatment for 36 months. During months 15 through 24 of the extension phase, patients receiving fingolimod once daily at 5.0 mg were switched to 1.25 mg. After 36 months of continuous fingolimod treatment, the annual relapse rate remained low (0.20-0.21) and 68% to 73% of patients remained relapse-free. At month 36, the majority of patients switched to or maintained on fingolimod were free from Gd-enhancing lesions (88%-89%) or new T2 lesions (70%-78%). The majority (76%-80%) of patients continuing in the extension were also free from 6-month sustained disability progression. Frequently reported adverse events associated with fingolimod during the placebo-controlled phase included dyspnea, diarrhea, and nausea; these were rarely reported during months 24 through 36 and the discontinuation rate (8.0%) was also halved compared with months 12 through 24.
Collectively, the results from these extension studies indicate sustained clinical and MRI benefit with extended laquinimod or fingolimod therapy in patients with RRMS, with good tolerability, especially at lower doses.
