A 3-year follow-up of the BENEFIT trial has shown that patients with CIS treated with interferon (IFN) continue to experience delay in conversion to clinically definite MS (CDMS).¹ The initial 2-year, double-blind portion of BENEFIT had found that IFN (250 SC every other day) significantly delayed time to diagnosis of CDMS (P<0.0001) and MS according to the McDonald criteria (P<0.0001).² The follow-up phase enrolled 261 patients who had received active therapy and 157 who had received placebo during the double-blind phase.¹ A total of 233 patients in the first (“early treatment”) group chose to continue therapy with IFN and 145 patients in the second (“delayed treatment”) group chose to initiate such therapy. At 3 years, CDMS had developed in only 37% of the early treatment group versus 51% of the delayed-treatment group. Early treatment thus reduced the risk of CDMS by 41% (hazard ratio, 0.59; 95% confidence interval [CI], 0.44 to 0.80; P=0.011). Early treatment also reduced the risk for progression of disability (according to the Expanded Disability Status Scale [EDSS]) by 40% (P=0.022).

Using revised criteria for CDMS, a reanalysis of data from the CHAMPS study confirmed the original findings, namely, that early treatment with intramuscular (IM) IFN delays conversion to CDMS in patients with CIS.³ According to the newer criteria (which had not been established when the CHAMPS study was initiated), a diagnosis of CDMS may now be confirmed on the basis of a new clinical episode or new lesion on magnetic resonance imaging (MRI).^3,4 As in the past, the diagnosis still requires 2 or more areas of involvement within the central nervous system (clinically or by MRI) consistent with demyelination, and occurring at separate points in time. Among 383 randomized patients, the 2-year risk of CDMS was reduced by 46% with IM IFN versus placebo; the 5-year incidence was 36% for the early treatment group versus 49% for the delayed treatment group (P=0.03).

An interim analysis from the PreCISE study has suggested that glatiramer acetate significantly reduces the risk of developing MS and delays development of CDMS in patients with CIS.⁵ Among 481 randomized patients with CIS and lesions typical of MS on brain MRI, the risk of developing CDMS was reduced by 44% with glatiramer acetate versus placebo, and the time to development of CDMS was delayed by 386 days more than in the placebo group. The proportion of patients who developed MS was 25% with glatiramer acetate as opposed to 43% with placebo. Although patients were originally slated to receive randomized treatment for up to 36 months, the interim findings prompted an early halt to the trial, giving all the participants (including the placebo group) the opportunity to receive glatiramer acetate for 2 years.

The use of SC IFN 44 once weekly in CIS (compared with SC IFN 44 3 times weekly and placebo) is currently being investigated in a phase III trial whose objective is to evaluate the delay to conversion to CDMS over 96 weeks in approximately 260 patients with CIS who have an abnormal MRI.⁶

A higher dose of glatiramer acetate is currently being compared with the approved dose in a trial of patients with relapsing–remitting MS (RRMS).⁷ Patients (n=980) are being randomized to once-daily doses of either 20 mg SC (the currently approved dose) or 40 mg. The primary endpoint is relapse rate at the conclusion of a 12-month, double-blind phase. A previous 9-month study (FORTE) of 90 patients with RRMS found trends favoring the higher dose with respect to total number of gadolinium-enhanced lesions, time to first relapse, and relapse rate.⁸