Oral MS Drugs Promising - Studies

Friday Jan 22, 2010 (foodconsumer.org) -- According to three studies published Jan 21 in the New England Journal of Medicine, experimental drugs Fingolimod and Cladribine, if given orally, may be used to treat multiple sclerosis. 

The typical treatments for MS are periodic infusions or injections; an inconvenient form of treatment. 

A study, let by Gavin Giovannoni and colleagues from the Blizard Institute of Cell and Molecular Science showed that patients who took Cladribine tablets were at a lower risk of relapse; their brain lesion count on magnetic resonance imaging was also effectively lowered. 

The study involved 1326 patients who were either given cladribine or a placebo in two or four short courses for the first 48 weeks, then in two short courses beginning on weeks 48 and week 52 for 8 to 20 days per year.  The primary outcome considered in the trial was the rate of relapse at 96 weeks. 

Specifically, The rate of relapse for those who took cladribine in a dose of 3.5 mg or 5.25 mg per kilogram were 0.14 and 0.15 respectively, compared to 0.33 for the patients on the placebo. 

The risk of sustained, 3 month progression of disability was reduced in the cladribine group by 33 to 31 percent, depending on the dose, with comparison to the placebo group. 

However, adverse effects were more frequent in the cladribine group than the placebo group.   Of those who took 5.25 mg per kg of body weight, 31.5 percent experienced lymphocytopenia compared to 1.8 percent in the placebo group; while none of the placebo recipients got herpes zoster, 12 of the patients taking the cladribine did.   

 The researchers acknowledged that "the benefits need to be weighed against the risks." 

Another trial led by Ludwig Kappos and colleagues at University Hospital, Petersgraben 4, CH 4031, Basel, Switzerland (along with other organizations) showed that another oral, experimental drug called Fingolimod helped MS patients better than a placebo. 

This trial involved 1272 patients with relapsing remitting multiple sclerosis, aged 18 to 55, who had a score of 0 to 5.5 on the Expanded Disability Status Scale, which ranges from 0 to 10 with the higher score indicating worse disability. 

In the trial, patients were assigned either 0.5 mg or 1.25 mg of Fingolimod or a placebo daily. The primary outcome was the annualized relapse rate and the time to disability progression.  

The researchers found the relapse rate for those who used 0.5 mg was 0.18 compared 0.16 for those who used 1.25 mg of fingolimod and 0.40 for those on the placebo. 

The drug in the dose of 0.5 mg and 1.25 mg over a 24-month period reduced the risk of disability progression by 30 percent and 32 percent, respectively, in comparison to the placebo group. 

The likelihood for disability progression was 17.7 percent for those using 0.5 mg of fingolimod, 16.6 percent for those using 1.25 mg and 24.1 percent for those who were given the placebo. 

About 18 percent of patients dropped out of the trial because of adverse events related to fingolimod like "bradycardia and atrioventricular conduction block at the time of fingolimod initiation, macular edema, elevated liver-enzyme levels, and mild hypertension." 

Similarly, the authors concluded that oral fingolimod improved the relapse rate and reduced the risk of disability progression and end points of MRI, but "the benefits need to be weighed against possible long term risks." 

The third trial led by Jeffrey A Cohen and colleagues at Neurologic Institute, Cleveland Clinic, in conjunction with several other organizations was to test oral fingolimod against intramuscular interferon for relapsing multiple sclerosis. 

The results of the trial showed that oral fingolimod had superior efficacy at cutting relapse rates and MRI outcomes in MS patients compared to intermuscular interferon beta-1a. 

This study enrolled 1292 patients with relapsing remitting multiple sclerosis who were assigned either oral fingolimod at a daily dose of 1.25 or 0.5 mg or intramuscular interferon beta-1a at a weekly dose of 30 ug. 

Eighty nine percent completed the study.  The relapse rates were significantly lower in those using fingolimod, 0.20 for those receiving 1.25 mg of fingolimod and 0.16 for those given 0.5 mg daily versus 0.33 for those using beta-1a. 

In terms of progression of disability, there was no difference between the two drugs. 

The trial report states in its abstract " Two fatal infections occurred in the group that received the 1.25-mg dose of fingolimod: disseminated primary varicella zoster and herpes simplex encephalitis. Other adverse events among patients receiving fingolimod were nonfatal herpesvirus infections, bradycardia and atrioventricular block, hypertension, macular edema, skin cancer, and elevated liver-enzyme levels." 

The authors wrote "Longer studies are needed to assess the safety and efficacy of treatment beyond 1 year."