Fingolimod Versus Interferon Beta 1b in Cognitive Symptoms (Cognition)

• To evaluate how the effects on cognitive dysfunction progression are associated to the effect of slowing the brain volume reduction at MRI (antiatrophic effect) that DMDs might have in RRMS patients, in the brain as a whole and in specific brain regions. [ Time Frame: 18 months ] [ Designated as safety issue: No ]
• Evaluate in a subgroup of patients if and to what extent optical nerve atrophy as assessed by RNFL thickness is predictive of the atrophy of the relevant brain regions and of cognitive deterioration and to what extent this is affected by DMD treatment. [ Time Frame: 18 months ] [ Designated as safety issue: No ]
• To evaluate if fingolimod has effects on depression in MS and how the effects of fingolimod and interferon beta 1b on brain atrophy, on cognitive dysfunction progression and on depression in MS are associated. [ Time Frame: 18 months ] [ Designated as safety issue: No ]
• To evaluate changes in quality of life, by mean of the MSQoL54 scale, upon initiation of treatment with fingolimod 0.5 mg. [ Time Frame: 18 months ] [ Designated as safety issue: No ]
• To evaluate changes in fatigue (mFIS, total score and scores of the 3 individual domains). [ Time Frame: 18 months ] [ Designated as safety issue: No ]

The purpose of this pilot study is to evaluate, by means of a specific cognitive test battery (Brief Repeatable Battery and Delis-Kaplan Executive Function System scale), the slowing/reduction of cognitive dysfunction progression in RRMS patients after 18 months of treatment with fingolimod in comparison with interferon beta 1b treatment, and to evaluate which test of the battery is the most sensitive in detecting differences between treatment groups.

• Drug: Fingolimod
• Drug: Interferon beta 1b

• Experimental: Fingolimod
  Intervention: Drug: Fingolimod
• Active Comparator: Interferon beta 1b
  Intervention: Drug: Interferon beta 1b

Inclusion Criteria:

• Patients with relapsing-remitting forms of MS defined by 2005 revised McDonald criteria.
• Patients with active disease, defined as at least one clinical relapse in the last year, or two clinical relapses in the last two years if there are signs of disease activity at one brain MRI scan performed in the last six months.
• Patients with cognitive impairment at screening, defined as at least one test of the Rao's Brief Repeatable Battery with scores falling outside the 90th percentile of the normative data.

Exclusion Criteria:

• Patients who had already been treated with multiweekly interferon (interferon beta 1b, or beta 1a multiweekly) and had an unsatisfactory response according to the judgment of the investigator.
• Patients with hyperactive forms of the MS disease according to the judgment of the investigator.
• Patients with an EDSS score higher than 5.
• Patients with a prior or current diagnosis of Major Depression according to DSM-IV.
• Patients with a history of chronic disease of the immune system other than MS such as known immunodeficiency syndrome.

Other protocol-defined inclusion/exclusion criteria may apply