November 8, 2021 | News | MS Research MS Treatments

Update on infusion therapies for MS

The previous article on MSology summarized some of the recent data on injectable and oral therapies for MS that were presented at the annual meeting of the European Committee for Treatment and Research in MS (ECTRIMS). We continue our ECTRIMS coverage with an update on infusion therapies for MS – Tysabri, Ocrevus and Lemtrada.

COVID-19

The foremost concern during the pandemic has been the safety of higher-efficacy medications and several groups have been collecting data to address this question. People with MS have an estimated 20% higher risk of dying from COVID than those in the general population (Prosperini and colleagues. ECTRIMS 2021; abstract P759. Evangelou and colleagues. ECTRIMS 2021; abstract P142). This is likely due to the higher proportion of people in the MS population with known COVID risk factors, such as disability and other chronic medical illnesses. But it is important to note that the mortality rate varies widely among different countries – from less than 1% in Sweden to almost 4% in the U.S. (Sormani M. ECTRIMS 2021).

Among the approved MS medications, only Ocrevus is associated with a higher risk of severe COVID-19; the risk of hospital admission is 1.6-fold higher with Ocrevus than with Copaxone, according to the Global Data Sharing Initiative (Simpson-Yap and colleagues. ECTRIMS 2021; abstract 098). One might think that the need to go to an infusion centre for treatment contributes to this higher risk, but this does not appear to be the case. The risk of severe COVID was about 1.8-fold higher with Ocrevus compared to Tysabri (which also requires a trip to an infusion centre). The risk of severe COVID is seen at the start of Ocrevus treatment and continues to increase with ongoing therapy (Sormani M. ECTRIMS 2021).

One way to avoid higher COVID risks could be to reduce the frequency of dosing. Several groups have looked at whether less frequent dosing (resulting in a lower dose) will still control MS disease activity. One MS centre in the U.S. tried delaying the 6-monthly infusions of Ocrevus by two months and found little to no loss of efficacy (Smoot and colleagues. ECTRIMS 2021; abstract P639). A second group tried personalized dosing – tailoring the dose according to blood test results – and found that this worked as well as a one-size-fits-all approach to dosing (Allen et al. ECTRIMS 2021; abstract P826).

Less frequent dosing also appears to be a good strategy with Tysabri, in this instance to lower the risk of developing PML (progressive multifocal leukoencephalopathy), a potentially fatal brain infection caused by the JC virus. In the NOVA trial, switching to dosing every 6 weeks appeared to be as effective as the usual dosing of once every 4 weeks (Foley and colleagues. ECTRIMS 2021; abstract P970). Similar efficacy results were seen at an MS clinic when Tysabri dosing was switched to every 6 weeks (Bernardes and colleagues. ECTRIMS 2021; abstract P787).

When selecting among different MS therapies, COVID vaccination has complicated the picture to some degree. Some infusion drugs, such as Tysabri and Lemtrada, do not appear to have an impact on a person’s response to COVID vaccination (Sormani M. ECTRIMS 2021). One study reported that people on Tysabri had the same immune response to vaccination as people without MS (Rechtman and colleagues. ECTRIMS 2021; abstract P781).

In contrast, Ocrevus specifically targets B cells, which are needed to produce the antibodies that fight the COVID virus. Numerous studies have now reported that Ocrevus will significantly impair a person’s ability to mount an antibody response to COVID infection (Kakara and colleagues. ECTRIMS 2021; abstract 129. Jaber and colleagues. ECTRIMS 2021; abstract P671. Weinstock-Guttman and colleagues. ECTRIMS 2021; abstract P630). That said, Ocrevus does not impair all immune responses to the COVID virus – which means that it is still worthwhile to get vaccinated (Kakara 2021). But some experts are now saying that a booster vaccine would be beneficial to top up a person’s immune response (Sormani M. ECTRIMS 2021; abstract 099).

Long-term data

Tysabri has seen a resurgence over the past year, likely because it does not significantly impair the immune response – an important advantage during a pandemic. Over the longer term, several new studies have reported that Tysabri continues to be highly effective. An analysis of the MS registry in Austria found that MS generally remained stable over an average 9-year treatment period; about 16% taking Tysabri experienced worsening disability and about 22% showed an improvement in their disability level (Guger and colleagues. ECTRIMS 2021; abstract P752). A Swedish study found that physical and mental symptoms of MS improved over an 11-year period with Tysabri (Ekstrom and colleagues. ECTRIMS 2021; abstract P738). In Ireland, the level of disability improved in one-third of people in the first three years of Tysabri treatment (McGuigan and colleagues. ECTRIMS 2021; abstract P261). The caveat, however, with long-term therapy is the cumulative risk of PML, so people are often switched off Tysabri after a couple of years.

Long-term data are also available from the OPERA trial of ocrelizumab. After 7 years on treatment, relapses became increasingly uncommon. About 1 in 4 people on continuous Ocrevus experienced a worsening of their disability (compared to 6 months before); about 8-9% required a cane or other walking aid at the end of the observation period (Giovannoni and colleagues. ECTRIMS 2021; abstract P723).

Also noteworthy were the long-term outcomes of people enrolled in Lemtrada studies for over 10 years. In CARE-MS I, which looked at previously untreated people, about one-half received the standard two courses of treatment and no other medication; the other half of the group were re-dosed with Lemtrada or another medication (Coles and colleagues. ECTRIMS 2021; abstract P733). Disability levels were stable in about 75% of people over a 10-year period. A similar picture emerged in the long-term results of CARE-MS II, which enrolled people who had previously been on another medication. In this study of generally more severe MS, about 60% required additional treatment after the initial two-year course of Lemtrada therapy (Giovannoni and colleagues. ECTRIMS 2021; abstract P722). The level of disability remained stable in about 70% of people. Unfortunately, in both studies, about 40-50% developed thyroid problems. That issue, and the need for close monitoring for years after stopping treatment, have prompted many doctors to opt for Ocrevus instead, which has a better safety profile.

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