Dr. Ontaneda: That is a great question. At the recent European Committee for Treatment and Research in Multiple Sclerosis meeting [ECTRIMS 2013] in Denmark, several presentations actually addressed that very question.
I'll start off by discussing the TOPIC study.1 So, TOPIC was a double-blind, placebo-controlled study that examined patients with clinically isolated syndrome [CIS] and found that teriflunomide, at doses of 7 mg and 14 mg, [significantly] reduced the conversion from clinically isolated syndrome to clinically definite MS. Both doses were also effective in the reduction of relapses and new MRI lesions. These results are important as they confirm that oral agents can be used early and they can delay the onset of MS. And certainly this will help prevent the accrual of disability when the agents are used in the earliest stages of multiple sclerosis.
This is in line with results of the oral cladribine in CIS study, which is also known as ORACLE [Oral Cladribine in Early MS].2 This study was actually presented at the American Academy of Neurology Annual Meeting this past March . ORACLE examined patients with a first demyelinating event—the definition of CIS was slightly different in ORACLE—and they basically randomized treatment of patients to placebo or oral cladribine. And the doses of oral cladribine were 5.25 or 3.5 mg[/kg]. Patients were followed for 96 weeks, and cladribine was found to reduce the risk of clinically definite MS by 61.9% and 67.3%, respectively.
These are important data. Although the development of cladribine has been halted—and that was due to a concern of malignancy found in phase 3 trials in
We are also interested in collecting further data regarding the effect of early treatment in our injectable agents and our infusion agents.
Narrator: Several trials reported at ECTRIMS 2013 showed that earlier initiation of natalizumab treatment results in reductions in MS disease
Dr. Ontaneda: A poster was also presented at the ECTRIMS meeting that demonstrated benefits of early treatment with natalizumab in the six-year follow-up data of the STRATA study.5 The study basically gathered long-term follow-up from open-label extensions from several different natalizumab clinical trials. The most interesting observation of this study was the comparison between patients who started natalizumab earlier versus those who started the medication later in the individual clinical trials. And what the long-term data showed was that patients starting natalizumab earlier had fewer relapses overall and also had lower EDSS scores at the completion of the study, compared with those who had started it later.
It also demonstrated that patients who had accrued disability while off the medication in that first phase, when they were typically on a placebo medication, did not improve with subsequent treatment. Although this point does seem quite obvious, given the mechanism of action of
In line with the above results, also at ECTRIMS, data were presented from a large multinational cohort called MSBase.6 Basically, the MSBase registry is a worldwide network of MS centers that collects data from clinical practice.7 The study that was presented examined predictors of confirmed three- and
This was somewhat surprising because MRI is such an important prognostic factor in several other studies. But, nonetheless, what they did find was that treatment with a
In conclusion, I would say that there does appear to be a strong rationale for early treatment in multiple sclerosis, and it seems that this holds true also for our new oral therapies.