MS Activity Quickly Returns to Baseline After Stopping Tysabri

Given the not-inconsequential risk of PML with Tysabri (natalizumab) use in multiple sclerosis—particularly with prolonged use—neurologists have taken the unproven track of intermittently stopping the drug in an effort to reduce that risk. And although noone really knows if this measure leads to the intended result (ie, a reduced risk of PML), it almost certainly increases the risk of MS disease activity. But when the risk of disease activity returns and to what extent has been unknown—until now.

In an assessment of 1866 patients enrolled in pivotal Tysabri clinical trials* who stopped the drug (owing to the voluntary removal of the drug from the market in 2005), O'Connor et al found that disease activity** returned shortly after Tysabri was discontinued. Then disease activity peaked between 4 and 7 months but, importantly, did not "rebound" beyond baseline levels.

The study authors concluded,

These data indicate that a return of disease activity to pretreatment levels should be anticipated soon after natalizumab treatment is interrupted, underscore that the consequences of reucrrent MS disease activity should be weighed against potential benefits of PML risk reduction, and should motivate the search for suitable alternatives to a mere treatment interruption.

How to address the interruption of Tysabri therapy (which is taken, rightly or wrongly, as a given to reduce the PML risk) will be answered to some extent by the ongoing RESTORE study. This Biogen-sponsored multicenter US study, in which Tysabri therapy will be interrupted for 24 weeks, is designed to assess 1) how quickly the immune effects of Tysabri disappear; 2) when MS symptoms return; 3) if other immunomodulatory drugs (eg, interferon beta) can control MS symptoms; and 4) how quickly the effects of Tysabri return after resuming therapy. The estimated primary completion date of RESTORE is December of this year, and the estimated study completion date is December of 2012.

* The AFFIRM, SENTINEL, and GLANCE studies.
** As measured by the annualized relapse rate (ARR) and gadolinium-positive lesions on MR images.

PML = progressive multifocal leukoencephalopathy.