麻豆传媒

BARCELONA -- Results from two European cohort studies provide no clear answers on whether natalizumab (Tysabri) or fingolimod (Gilenya) offers better efficacy, researchers reported here.

One study from France found relapse rates to be lower with natalizumab, while another from Denmark revealed similar relapse rates in both groups. Both were reported during an oral session at the here.

Both drugs are approved for relapsing-remitting MS patients. They're two of the spate of treatments for MS that have been approved in recent years, and clinicians and patients would naturally like guidance on whether any are clearly to superior to the others. But few head-to-head comparisons and no randomized controlled comparisons of the safety and efficacy of these drugs have been done.

There have been some observational data, but the findings are mixed. Indeed, two other recent studies -- one by and the other by -- came to similarly conflicting results. The Braune trial found no difference between the two drugs over one year, while the Kalincik paper found higher relapse rates with fingolimod.

The French and Danish registry studies presented here sought to further clarify the issue.

The French trial, presented by , of CHU Nantes and Inserm in France, assessed clinical and MRI outcomes for relapsing-remitting MS patients from 27 specialized treatment centers in that country -- ultimately collecting prospective data on 326 patients treated with natalizumab and 303 treated with fingolimod.

They used two methods to control for differences in the populations: multivariate logistic regression and propensity score method based on the inverse probability of treatment weighting. These analyses attempted to control for five factors: gender, number of relapses in the previous year, presence of gadolinium-enhancing lesions, Expanded Disability Status Scale (EDSS) scores, and hospitalizations.

They found in the multivariate model that those on fingolimod had a significantly higher risk of relapse, new gadolinium-enhancing lesions, and new T2 lesions at two years compared with those on natalizumab.

They saw a similar increase in the risk of having at least one relapse, having at least one gadolinium-enhancing lesion, and at least one new T2 lesion at two years with fingolimod using the propensity score method.

Laplaud acknowledged that the study was limited by a lack of randomization and potential confounders that weren't taken into account, but he still concluded that the study provides class IV evidence that natalizumab has better efficacy than fingolimod over two years.

The Danish study, presented by , of the University of Aarhus in Denmark, assessed all Danish patients who started natalizumab or fingolimod in 2011 or later (fingolimod was approved that year, and natalizumab was already on the market).

In their initial analysis, they assessed 1,201 relapsing-remitting MS cases -- 531 on natalizumab, 670 on fingolimod -- and found a significant "but probably false difference" in relapse rates that favored fingolimod.

But then they deployed propensity score matching to diminish the amount of confounding in the population, ending up with 942 patients.

In that analysis, they found that annualized relapse rates were essentially the same, with no statistically significant difference between groups: 0.30 for natalizumab and 0.28 for fingolimod. The drugs were also equal in terms of time to first relapse and disease progression, he said.

A Kaplan-Meyer analysis found similar probabilities of remaining relapse-free over 3 years for patients in both drug groups (HR 1.08, P=0.40).

Koch-Henriksen noted that using propensity matching was useful for reducing bias in this type of analysis, and concluded that there was "no difference, not even a trend, between the disease activity in natalizumab and fingolimod treated relapsing-remitting MS patients."

"This study could not support that any of the two second-line treatments should be superior to the other," he said during the presentation, adding that convenience and safety should be a high priority when choosing between the two treatments.

, of University College London, who was not involved in the study, told 麻豆传媒 that conflicting results "are not unusual, particularly when it comes to this phase IV stage when one no longer has a perfectly randomized controlled situation."

, of the University of California San Francisco, who wasn't involved in the trial, noted several limiting factors for interpreting the results, including the fact that there may be differences in the way the drugs are used and in patient selection between France and Denmark.

"Clearly they both can't be right," Green told 麻豆传媒. "However, resolving which one is ultimately correct may be difficult. The size of the studies is not an explanation, as larger studies would tend to find effects that smaller studies lacked the power to detect. However, in this case the smaller study found a difference and one which was large enough that if it were true, should be seen in other studies."