Delayed Ocrevus Infusion May Increase MRI-based RRMS Risk

An interval of one month or longer was associated with a 5X higher risk of new or enlarging lesions

Marta Figueiredo, PhD avatar

by Marta Figueiredo, PhD |

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An extended interval between maintenance doses of Ocrevus (ocrelizumab) may increase the risk of MRI-based disease activity in people with relapsing-remitting multiple sclerosis (RRMS), according to a real-world, multicenter study in Italy.

In fact, an extended interval dosing (by one month or longer) was associated with a fivefold higher risk of MRI-based disease activity, defined as new or enlarging lesions or the presence of new lesions with active inflammation. This didn’t translate into an increased risk of clinical relapses or greater rates of confirmed disability progression, however.

Further studies with longer follow-up periods are needed to confirm these findings and determine whether Ocrevus’ extended interval dosing is safe in this patient population, the researchers noted.

The study, “Is It Time for Ocrelizumab Extended Interval Dosing in Relapsing Remitting MS? Evidence from An Italian Multicenter Experience During the COVID-19 Pandemic,” was published in Neurotherapeutics.

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Immunosuppressive disease-modifying therapies (DMTs) are a mainstay for people with multiple sclerosis (MS), but the COVID-19 pandemic has delayed many scheduled appointments for infusion DMTs, or those administered directly into the bloodstream.

“Such delays in treatment were reportedly not caused by fear of immunosuppressive drug use but rather by the general fear of contracting a fatal disease, which is often the case during traveling and hospital visits,” the researchers wrote.

Ocrevus, an infusion DMT, is approved for both relapsing forms of MS and primary progressive multiple sclerosis. The first two doses are administered two weeks apart at 300 mg, followed by 600 mg maintenance doses every six months.

While Ocrevus injections were frequently postponed by patients during the pandemic, the consequences of dosing delays remain largely unclear.

Standard vs. extended dosing intervals

To address this, researchers retrospectively analyzed clinical and MRI data from RRMS patients who received Ocrevus at standard versus extended intervals during the pandemic at nine Italian MS centers.

Extended interval dosing (EID) was defined as an infusion delay of at least four weeks, or about a month — representing an interval of at least seven months, instead of the standard six months.

Three infusions were considered for defining standard versus extended dosing intervals: the last infusion before January 2020 and two subsequent infusions up to June 2021.

The study included 278 patients (178 women, 100 men; mean age 43.2) who’d been living with the disease for a mean of 10.6 years and had received a mean of 1.9 DMTs before Ocrevus.

A total of 174 patients (62.6%) received all three Ocrevus injections at standard intervals (standard interval dosing, or SDI group), while 104 (37.4%) received at least one delayed infusion (EDI group).

Those in the EDI group had a significantly longer disease duration (12.1 vs. 9.7 years) and a significantly higher COVID-19 vaccination rate (64.4% vs. 48.9%) than those on standard dosing.

From January 2020 to June 2021, 18 patients (two in the EDI group) experienced 24 clinical relapses, 21 (six on the EDI group) showed new or enlarging lesions on MRI, and 12 (six in each group) had confirmed disability progression (CDP).

Increased risk

When adjusting for potential influencing factors, EDI was found to significantly increase the risk of MRI-based disease activity by 5.3 times, but not of clinical relapses or disability progression.

The team also found that a deficient B-cell depletion (10 or more B-cells per microliter) before the third infusion and a shorter time on Ocrevus treatment were significant risk factors for relapses, while a longer disease duration was associated with a greater risk of MRI-based activity.

In both groups, 97.1% of patients showed no evidence of disease activity in the six months after the third infusion, as defined by the absence of clinical relapses, new brain lesions, and CDP. This suggested EDI had no effect on this outcome.

This is in line with previous studies, which showed that B-cell-depleting DMTs have been delayed by one to three months during the pandemic, but “no major rebound in disease activity has been reported,” the researchers wrote.

“To our knowledge, this is the first report suggesting caution in use of the EID regimen due to MRI activity,” the team wrote.

While this does not seem to affect patients’ disability level, “as revealed by the lower rate of CDP observed in both groups, we cannot exclude a negative impact on disability accrual with longer follow-up,” they added.

Further studies following patients for longer periods are needed to confirm whether this increased risk of new brain lesions with delayed Ocrevus dosing is associated with “long-term changes in the disease course trajectory,” the researchers wrote.

Future research should also “determine whether the extension of a single infusion interval significantly affects disease progression over a longer period of time,” and analyze clinical and safety outcomes in patients on SID versus continuous EID, they concluded.

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