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AAN 2015 – Part 3
American Academy of Neurology 67th annual meeting
Washington, DC, April 18-25, 2015
Here is a summary of new studies of oral MS treatments presented at AAN 2015. In the next issue we’ll look at injectable/infusion medications.
Gilenya: An emerging benchmark of the impact of treatment is NEDA, short for ‘no evidence of disease activity’. This means that a person has no relapses, no new inflammatory activity on an MRI and no short-term progression of their disability. About 1 in 3 people can achieve NEDA over the first two years of treatment with one of the more potent MS medications (Gilenya, Tysabri and Lemtrada). Another factor that predicts how well someone with MS will do over the longer term is the rate of brain shrinkage (atrophy), which may reflect tissue loss due to inflammation. This has led to a new measure of treatment effect called NEDA-4 (for NEDA + brain atrophy). Since atrophy occurs in everyone due to aging, a cut-off value of roughly twice the atrophy rate seen in non-MS adults is used.
An analysis of people in the one-year TRANSFORMS study, which compared Gilenya to Avonex, has reported that people on Gilenya are about twice as likely to achieve NEDA-4 as those treated with Avonex (Montalban and colleagues. AAN 2015; abstract P4.001). Overall, about 28% achieved NEDA-4 with Gilenya compared to 17% with Avonex.
Aubagio: Two large studies (TEMSO and TOWER) have compared the efficacy of Aubagio with a placebo for up to three years in people with MS. A pooled analysis reported that Aubagio 14 mg/day reduced relapses severe enough to require hospitalization by about 60% (Macdonell and colleagues. AAN 2015; abstract P7.212). A pooled analysis of safety data found that the most common side effects were hair thinning, diarrhea and elevated liver enzymes (Leist and colleagues. AAN 2015; abstract P7.268). Most side effects were mild to moderate and resolved on their own. The rate of serious infections was low and similar to what was seen with placebo. Overall, 12.5% (vs. 7.5% on placebo) stopped treatment because of side effects. A separate analysis, which included data from the TOPIC trial of people with “pre-MS” (clinically isolated syndrome), also showed that Aubagio delayed the first relapse by 6-10 months (Honeycutt and colleagues. AAN 2015; abstract P7279).
Tecfidera: No new or surprising side effects have been seen in the long-term extension (called ENDORSE) of the two phase III studies of Tecfidera (Pozzilli and colleagues. AAN 2015; abstract P7.235). Less than 4% developed serious infections. However, a high proportion of people (14-26%) switching to Tecfidera from placebo or Copaxone dropped out because of side effects. Single-center studies reported that 4-18% stop Tecfidera in the first year because of side effects (Aboab and colleagues. AAN 2015; abstract P3.271; Smoot and colleagues. AAN 2015; abstract P3.269).
An integrated analysis of trial data found that the annualized relapse rate remained low (0.12-0.19) over the first five years of treatment (Bar-Or and colleagues. AAN 2015; abstract P7.229). The risk of disability progression also remained low (Bar-Or and colleagues. AAN 2015; abstract P7.234). A separate analysis from ENDORSE found that most people on Tecfidera reported (69-77%) improvements or stability in physical and mental functioning (Kita and colleagues. AAN 2015; abstract P7.236).
An emerging issue is the impact of treatment on white blood cell (WBC) counts. Only 4% had low WBCs in the DEFINE study and this didn’t seem to make people more susceptible to infections (Gold and colleagues. N Engl J Med 2012;367:1098-1107). However, a recent suggestion is that chronically low WBCs may have contributed to the one PML case reported with Tecfidera; the same issue of chronic immune suppression has been raised for the one PML case with Gilenya. After going through patient records at an MS centre, one group has found that about 1 in 4 people treated with Tecfidera for a year or more had chronically low blood counts (Longbrake & Cross. AAN 2015; abstract P3.240). It remains to be seen if low WBCs is important to PML risk.
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