An update on higher potency treatments for MS – ECTRIMS 2015
European Committee for Treatment and Research in MS (ECTRIMS) – 31st Congress – Barcelona, Spain, October 7-10, 2015 – High-efficacy medications are typically used for people with severe or worsening multiple sclerosis, or when the initial treatment isn’t as effective as it could be. The two medications in this category are Tysabri and Lemtrada, which are administered by a slow drip (infusion) in a clinic, hospital or infusion centre. Both of these drugs have been shown to be highly effective in short-term MS trials, and new studies presented at ECTRIMS 2015 show that both continue to work if you stay with the program.
How well do people do over the longer term?
Most clinical trials of new medications include an extension phase, in which people on the medication keep taking it and those in the comparator group (either a placebo or a different medication) are switched to the study medication. This enables researchers to get some sense of how well people will do over the longer term.
Long-term data for Lemtrada are available from two sources. Both of the phase III trials (called CARE-MS I and CARE-MS II) had extension phases, and these have now been running for a total of five years (2 years of the study + three years for the extension). These extensions are a little different from the usual studies. For people initially in the Lemtrada group, they took one course of treatment at the start, and a second course at one year. Thereafter, most people have received no MS medication so they have been without treatment for the subsequent three years.
CARE-MS I looked at people who hadn’t been treated before entering the study. For those in the Lemtrada group, relapses and inflammatory activity in the brain have been uncommon, and 80% of people have seen no worsening of their disability over the past five years (Havrdova and colleagues. ECTRIMS 2015; abstract 152. Arnold and colleagues; abstract P1100). In fact, disability has improved in 1 in 3 people. The CARE-MS studies used Rebif as the comparator. For those on Rebif for two years before switching to Lemtrada, people did much better after making the switch. The rate of relapses declined by two-thirds, about 3 in 4 had no relapses, and about 80% of people had no new inflammation in the brain and no worsening of their disability (Hartung and colleagues. ECTRIMS 2015; abstract P1096. Rovira and colleagues; abstract P1088).
Similar results were seen in CARE-MS II, which looked at people who hadn’t responded well to a previous MS therapy. After starting Lemtrada, about 80% of people no longer had relapses, and disability levels were unchanged or improved in about 3 of 4 people (Fox and colleagues. ECTRIMS 2015; abstract P1102. Traboulsee and colleagues; abstract 1103). These results show that Lemtrada continues to have an effect – remarkable because most people haven’t received any drug for 1-3 years.
The second source of long-term data is the Cambridge cohort. In the early 1990s, Lemtrada (called Campath-1H at the time) was tried in about a hundred people before the clinical trials got underway. So the drug has been used for about 10 years in people with relapsing-remitting MS (RRMS), and about 20 years in people with secondary-progressive MS (SPMS). For those with RRMS, there has been no change in disability over the past decade and people continue to have only mild to moderate disability (Brown and colleagues. ECTRIMS 2015; abstract P1504). About 1 in 2 have seen an improvement in their disability level over that 10-year span. Unfortunately, the same hasn’t been true for those with SPMS. Treatment appeared to do little to slow the progress of their disability. The same thing has been reported with Tysabri. It was recently announced that Tysabri was largely ineffective in a trial of people with SPMS (called ASCEND; the media release is available at www.businesswire.com/news/home/20151021005273/en/Biogen-Reports-Top-Line-Results-Phase-3-Study). What these results underscore is the importance of treating MS early before the SPMS phase begins. Once disability progression caused by neurodegeneration begins, the current MS treatments won’t provide much of a benefit.
Extension studies weren’t done for Tysabri. In part this was because of the problems that Tysabri encountered after it launched in 2004 – the drug was pulled from the market after a few people developed PML (progressive multifocal leukoencephalopathy), a potentially fatal brain infection. The drug came back on the market in 2006 despite this risk – there have been over 100 deaths since then – but many doctors are reluctant to keep people on the drug longer than two years.
However, some information about long-term use is available from the ongoing Tysabri Observational Program (or TOP). According to the most recent report, relapses are uncommon over 5-6 years of treatment (Butzkueven and colleagues. ECTRIMS 2015; abstract P1092). About 1 in 5 people experienced worsening disability. A separate analysis of Canadians in TOP found no change in disability after three years of treatment (Bhan and colleagues. ECTRIMS 2015; abstract EP1333). Results were even better in a Swedish study of Tysabri (Johansson and colleagues. ECTRIMS 2015; abstract 599). Disability scores on average showed some improvement over a five-year period. So these results indicate that Tysabri keeps on being effective over the longer term. Since Tysabri is typically used in people who aren’t doing well with their MS, it’s all the more remarkable that it can stabilize the level of disability for several years even in individuals with severe disease.
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