Latest news on MS treatments – injection/infusion agents
AAN 2015 – Part 4
American Academy of Neurology 67th annual meeting
Washington, DC, April 18-25, 2015
Part 3 summarized new studies of oral MS treatments. In this issue we’ll look at injectable/infusion medications.
Tysabri: Concerns that Tysabri dosing may be too high have led to studies in which the drug is administered less often than once every four weeks. A lower drug exposure may lower the risk of developing progressive multifocal leukoencephalopathy (PML), an often fatal brain infection associated with Tysabri use. A new study suggests that taking Tysabri every 8 weeks is as effective as the monthly schedule (Zhovtis Ryerson and colleagues. AAN 2015; abstract P3.267). Similar results were seen in a separate study in which Tysabri was taken every 6 weeks (Foley and colleagues. AAN 2015; abstracts P3.258 and P4.032). For people who need to stop Tysabri, slowly reducing the dose over four months may lower the risk of having a relapse, which can occur when the drug is withdrawn (Weinstock-Guttman and colleagues. AAN 2015; abstract P3.287).
Lemtrada: Two clinical trials (CARE-MS I and II) showed that Lemtrada was better than Rebif in reducing relapses and MRI activity, and slowing disability progression over two years (Cohen and colleagues. Lancet 2012;380:1819-1828; Coles and colleagues. Lancet 2012;380:1829-1839). Results at three and four years were reported last year (see ACTRIMS/ECTRIMS 2014 – Part 2. MSology, September 18, 2014).
In the extension of CARE-MS I (previously untreated people), 73% received two treatment courses over the first two years and didn’t require further treatment (Compston and colleagues. AAN 2015; abstract S4.007). Relapse rates remained low after four years (average 0.21/year). Overall, the amount of disability was generally stable, and 30% of people actually had less disability. In year 4 of treatment, 70% had no inflammatory activity on their MRI (Arnold and colleagues. AAN 2015; abstract P7.246). Infections were common, but were generally mild and became somewhat less common over time (46% in year 4) (Jung Henson and colleagues. AAN 2015; abstract P7.265).
In the extension of CARE-MS II (previously treated people), 68% of people didn’t require further treatment after the first two courses (Havrdova and colleagues. AAN 2015; abstract P7.276). Relapse rates remained low (0.23) in year 4. Over the first four years, 76% showed no progression of their disability; about 40% had an improvement in their disability scores. For the group switching from Rebif to Lemtrada, relapse rates were reduced 71% and 15% saw a reduction in their disability score (Fox and colleagues. AAN 2015; abstract P7.278).
Daclizumab: This new drug in development is a monoclonal antibody that blocks activation of immune cells (T cells). It’s given by subcutaneous (under the skin) injection every four weeks. The DECIDE study compared daclizumab with Avonex in 1,841 people with MS (Kappos and colleagues. AAN 2015; abstract S4.003). Daclizumab was better than Avonex with respect to reducing the number of new MRI lesions at 96 weeks, but the two drugs were not significantly different in slowing disability. Serious side effects (15% vs. 10%) and stopping treatment due to side effects (14% vs. 9%) were more common with daclizumab compared to Avonex (Selmaj and colleagues. AAN 2015; abstract P7.230). The most common problem with daclizumab was upper respiratory tract infections, whereas flu-like illness was more common with Avonex.
DECIDE is the second of two large studies of daclizumab. The first study, SELECT, compared the drug to a placebo for one year (Gold and colleagues. Lancet 2013;381:2167-2175) (see New results for two novel therapies, MSology, August 7, 2014.). A one-year extension of that study was called SELECTION. Those who completed SELECTION could then enter SELECTED, the long-term follow-up study. About 30% of people from the original study dropped out before entering SELECTED, which may indicate that future results will be overly pre-selected. Treatment effects appear to be sustained during year 3 (Radue and colleagues. AAN 2015; abstract P7.226). However, another 23% have dropped out or interrupted treatment after a median of 25 months due to side effects (Gold and colleagues. AAN 2015; abstract P7.225). Infections (50%) and skin reactions (26%) are common, although serious infections (3%) or skin problems (2%) don’t appear to be that frequent. A potential concern is that 1% developed symptoms suggestive of colitis, which may be associated with the effects of daclizumab on the immune response. This will require further investigation.
Studies to watch for:
- TOPAZ, a follow-up study of people treated with Lemtrada to examine the long-term efficacy and safety of treatment (Brinar and colleagues. AAN 2015; abstract P7.219).
- TREAT-MS, which will look at the impact of Lemtrada on quality of life and employment (Engelmann and colleagues. AAN 2015; abstract P7.281).
- OPERA I and II, two studies of ocrelizumab (a B cell-directed therapy in development) in relapsing-remitting MS. The drug is administered by intravenous infusion (slow drip) every six months (Hauser and colleagues. AAN 2015; abstract P7.201). Ocrelizumab will be compared with Rebif.
- ORATORIO, a new phase III study of ocrelizumab in people with primary-progressive MS (Montalban and colleagues. AAN 2015; abstract P7.017)
- SYNERGY, which is studying whether the investigational drug BIIB033 can promote remyelination of damaged nerve fibres (Cadavid and colleagues. AAN 2015; abstract P7.204). The drug blocks a protein (called LINGO-1) that impedes new myelin formation. BIIB033 is administered by injection every four weeks and will be used in combination with Avonex.
- SPRINT-MS, a phase II trial of ibudilast in primary- and secondary-progressive MS (Fox and colleagues. AAN 2015; abstract P7.214). Ibudilast may reduce immune activation in the brain. A prior phase II study found it didn’t reduce inflammatory lesions, but it did appear to slow the rate of tissue loss in the brain (Barkhof and colleagues. Neurology 2010;74:1033-1040).
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