What did COVID teach us about MS therapies? – Part 1

The COVID pandemic redefined how people would live their lives in 2020 and raised important questions about the best approach to treating multiple sclerosis. The emphasis in recent years has been to use more potent therapies earlier on in the course of illness but the pandemic caused some to push the Pause button. Would immune-suppressing therapies leave people more vulnerable to the CoV-2 virus? Potent therapies were known to increase the risk of infection by some degree – but that was before there was a high level of infections in the community. So in weighing the benefits and risks of treatments, how does a pandemic change the risk profile?

These concerns caused many to take a second look at the traditional first-line therapies for MS – the injectable agents (interferons, Copaxone) and the orals (Tecfidera, Aubagio). The pandemic was a reminder that many people do well on an injectable or oral treatment. There was also a recognition that in some cases, people on a potent medication can be switched to a less risky therapy – at least until the pandemic passes.

The following is our look back at the some of the research highlights of 2020 regarding the use of injectable and oral medications for MS. In Part 2 we’ll look at the year’s research into higher potency medications.

Interferon-beta (Avonex, Rebif, Betaseron/Extavia, Plegridy): This class of medication was originally embraced for its antiviral effects, causing some to suggest that they might confer some degree of protection against the CoV-2 virus. Indeed, preliminary studies of Betaseron and Rebif suggested some benefit when used as part of a multi-drug cocktail (Hung and colleagues. Lancet 2020, epublished May 8, 2020. Davoudi-Monfared and colleagues. Antimicrob Agents Chemother 2020;64:e01061-20). But these results are not conclusive and more research is needed. At the very least it appears that it’s safe for people to continue on their interferon regimen during the pandemic.

Aubagio: A new analysis found that Aubagio continues to be effective for up to 6 years and people’s level of disability generally remained stable (Miller and colleagues. Mult Scler Relat Disord 2020;46:102438). A separate study found that quality of life improved during Aubagio treatment although there didn’t appear to be much of an impact on fatigue (Prieto Gonzalez and colleagues. ECTRIMS 2020; abstract P0349). Remaining on treatment with Aubagio is considered to be safe during the pandemic, with some people pointing to a possible antiviral effect of the drug (Bilger and colleagues. Oncotarget 2017;8:44266-44280). Thus far, case reports have indicated that people on Aubagio who contract COVID appear to well and their MS doesn’t worsen (Maghzi and colleagues. J Neurol 2020;267:2790-2796).

This year also saw the start of a study investigating a new treatment called vidofludimus, which is the next medication in the Aubagio class (Muehler and colleagues. Mult Scler Relat Disord 2020;43:102129). Watch for more on this treatment over the next few years.

Tecfidera: This year saw the release of long-term data, with some people remaining on treatment for up to 13 years (Gold and colleagues. ECTRIMS 2020; abstract FC02.05). People who stayed on treatment continued to benefit, with 45% remaining relapse-free and 72% seeing no worsening of their disability. Also noteworthy was the RESPOND study, which showed that people had substantially fewer relapses after switching from Copaxone to Tecfidera (Repovic and colleagues. Neurol Ther 2020; epublished November 23, 2020).

Tecfidera reduces the number of immune cells, which raised some concerns about people’s immunity during the pandemic. So it was timely that one study reported that the fluctuations in the number of immune cells seen during treatment with Tecfidera do not appear to increase the risk of infection (Boffa and colleagues. CNS Drugs 2020;34:425-432).

Coming soon is a next-generation formulation of Tecfidera, which was approved by the FDA this year and is expected in Canada in 2021. The new drug, called Vumerity, was shown to cause less stomach upset than Tecfidera in the EVOLVE-MS-2 study (Naismith and colleagues. CNS Drugs 2020;34:185-196).

Vaccination

Perhaps the most important issue in 2021 will be how well people on an MS treatment will respond to a COVID vaccine. Vaccines and MS medications have opposing effects: vaccines stimulate the immune response whereas MS medications reduce the abnormal immune response seen in MS. So there is a potential for an MS drug to inhibit a person’s immune response to a vaccine – an important issue when it comes to more potent MS medications.

Fortunately, numerous studies have shown that interferons do not reduce the effectiveness of a vaccine (Schwid and colleagues. Neurology 2005;65:1964-1966. Mehling and colleagues. PLoS One 2013;8:11). In contrast, the vaccine response is somewhat reduced with Copaxone but it’s probably sufficient to fight off infection (Olberg and colleagues. Mult Scler 2014;20:1074-1080).

The story is similar with the oral drugs. Aubagio appears to blunt the vaccine response to some degree (like Copaxone) but people would be expected to respond (Bar-Or and colleagues. Neurol Neuroimmunol NeuroInflammation 2015;2:e70). The response to a wide range of vaccines during treatment with Tecfidera appears to be similar to what’s seen with an interferon, so a COVID vaccine should be effective (von Hehn and colleagues. Neurol Neuroimmunol Neuroinflamm 2017;5:e409). So overall, these results suggest that people taking an injectable medication, Aubagio or Tecfidera will be in a good position when a COVID vaccine becomes available.


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