Clinically isolated syndrome (CIS) will evolve into either benign multiple sclerosis (B-MS) or nonbenign multiple sclerosis (MS). In light of the fact that treatment of B-MS with disease-modifying drugs may be unnecessary, the differentiation of this B-MS from nonbenign MS is important.¹ As of yet, however, no clinical or paraclinical markers have been validated for the early identification of patients who will to have a benign course of disease.¹

Within the past 5 years, clinical trials of disease-modifying drugs have been enrolling patients at earlier stages of their MS disease course than did older studies. As a result, lower disease activity in patients makes statistically significant outcomes more difficult to achieve. Data from the REGARD study (REbif vs Glatiramer Acetate in Relapsing MS Disease) showed no significant differences between subcutaneous (SC) interferon (IFN) β-1a and glatiramer acetate with respect to time to first relapse in patients with relapsing-remitting MS (RRMS).²² The authors noted that the relapse rates in both treatment groups were much lower than expected and were also lower than those in previous trials in patients with RRMS.²² They commented that the ability to show differences between therapies in the head-to-head REGARD study (contrasted with separate placebo-controlled studies of each drug) was challenged by a trial population that had low disease activity.²² [Editor’s Note:The results of the REGARD trial should not be taken to imply that a significant difference would have been observed had the trial been conducted earlier with a patient population with more active disease. It is possible that the relative equivalence in efficacy of both drugs is not the result of a patient population with lower disease activity but rather due to similar effects in the reduction of relapses.] Because trials are enrolling patients earlier in the course of their MS, research is now better able to pinpoint the progression of CIS to MS. Studies have confirmed that early treatment with disease-modifying drugs prolongs the time to conversion to clinically definite multiple sclerosis (CDMS). For instance, the CHAMPS study (Controlled High-Risk Subjects Avonex Multiple Sclerosis Prevention) showed that the cumulative probability of developing CDMS was significantly lower among patients with CIS who received intramuscular (IM) IFN β-1a than in those who received placebo.²³ The ETOMS study (Early Treatment of Multiple Sclerosis) confirmed that SC IFN β-1a significantly reduced the proportion of patients with CIS who converted to CDMS and reduced the overall frequency of relapses compared to placebo.²⁴ In the recently published PreCISe trial (Early Glatiramer Acetate Treatment in Delaying Conversion to CDMS in Subject presenting with a CIS), glatiramer acetate significantly reduced the risk of developing CDMS and prolonged the time to conversion to CDMS compared to placebo in patients with CIS.²⁵ Moreover, follow-up analyses from the BENEFIT trial (Betaseron in Newly Emerging Multiple Sclerosis for Initial Treatment) have demonstrated that patients with CIS treated with IFN β-1b continue to experience delays in conversion to CDMS over 5 years.²⁶

In addition to these favorable developments, the ability to predict the disease course from the time of CIS diagnosis is continuing to evolve. It remains to be seen whether the trend toward earlier enrollment of patients in clinical trials will yield a greater proportion of individuals with B-MS than has been historically observed. Also of interest will be insights into the percentage of patients in CIS trials who have or have not converted to CDMS at the latest follow-ups.