ACTRIMS/ECTRIMS 2014 – Part 2
Update on infusion drugs
We continue our coverage of this year’s ACTRIMS/ECTRIMS congress with a summary of new data on MS therapies administered by intravenous (into the vein) infusion.
Tysabri (natalizumab): People taking Tysabri are often advised to stop treatment after two years because cumulative exposure to the drug substantially increases the risk of developing PML (progressive multifocal leukoencephalopathy), a debilitating and often fatal brain infection. So no long-term studies have been available until now. An Italian study looked at 378 people on Tysabri for up to six years (Prosperini and colleagues. ECTRIMS 2014; abstract P292). Overall, two-thirds of people either stopped taking the treatment because of concerns about PML or skipped treatment for a few months at a time. Among those who stopped the drug, 39% had some worsening of their disability compared to 6% who stayed on treatment and 23% who took periodic breaks.
During the initial approval process for Tysabri, the Food and Drug Administration raised some concerns about the dose (300 mg once a month), which was much higher than the doses that were originally tested. Lower dosing has re-emerged because it may reduce the risk of developing PML. A U.S. study has looked at whether less frequent dosing – every 7-8 weeks rather than every 4 weeks – makes any difference (Zhovtis Ryerson and colleagues. ECTRIMS 2014; abstract P287). Those taking Tysabri every two months actually did better than those on the regular schedule; while this may be due to bias in the analysis, they did appear to do at least as well as those taking Tysabri every month. So this may be an option for some people. However, it hasn’t been determined yet if less frequent dosing lowers the PML risk.
An under-researched area is whether MS therapies have an impact on the cognitive problems seen in MS (memory, difficulty planning, finding the right word, etc.). A small study found that people taking Tysabri for two years showed some improvement in their cognitive performance (Doehler and colleagues. ECTRIMS 2014; abstract P327). However, some of this effect was due to improvements in MS fatigue, which can impact cognitive test scores. So it’s unclear if improved cognitive function was due to Tysabri’s effects on the brain or on MS fatigue.
Lemtrada (alemtuzumab): The newest MS therapy (approved in many countries but not the U.S.) presented a number of long-term results. Data were based on extensions of the two phase III studies of the drug (called CARE-MS I and CARE-MS II). So after the two-year studies, people could enroll in the extension and have now continued on treatment for an additional two years. One curious feature of Lemtrada, however, is that the drug is only dosed annually – an initial five-day course of infusions, followed by a three-day course a year later. Because the drug’s effects on the immune system last for years, people could continue in the extension studies without actually receiving any additional doses. What this means is that the four-year results are generally for people who have not taken Lemtrada (or any other MS drug) for the past two years. Thus far, 68-73% of people have not required additional medication and their MS remains well controlled (Coles and colleagues. ECTRIMS 2014; abstract P090; Hartung and colleagues. ECTRIMS 2014; abstract P043). Relapse rates for newly-treated people were low in years 3 and 4 (an average of 0.16 relapses/year over the four years), and disability levels were stable or improved in 3 out of 4 people on the drug.
In year 3 (i.e. no treatment for one year), most people had no relapses or new inflammatory activity on their MRI (Arnold and colleagues. ECTRIMS 2014; abstract FC2.2; Fisher and colleagues. ECTRIMS 2014; abstract P103). In addition, 23-30% showed no evidence of disease activity (i.e. no relapses, no new MRI activity, no disability progression) over the three-year time period (Havrdova and colleagues. ECTRIMS 2014; abstract FC1.4). So these results show that treatment continues to be effective despite no additional courses of medication in years 3 or 4.
Rituxan (rituximab): The first B cell drug tested in MS was Rituxan, originally developed for blood cancers (and no longer in development for MS). A new study in people with secondary-progressive MS found that 45% showed some improvement with treatment, and disability progression was stabilized in another 38% (Perrone and colleagues. ECTRIMS 2014; abstract P286). These results suggest that targeting B cells may help people with SPMS, and fortunately there are two of these drugs (e.g. ofatumumab and ocrelizumab) currently being developed.
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