No Increase in Disease Activity With Longer Lag in Rituximab Treatment

Longer infusion intervals may ease side effects of therapy in RRMS

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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People with relapsing-remitting multiple sclerosis (RRMS) who are stable on rituximab treatment may receive the therapy at extended intervals without risking increased MS disease activity, according to a new study.

In fact, a longer lag between infusions could potentially reduce the medication’s side effects, researchers say — noting, however, that more studies are needed to determine the safety profile of so-called dose interval extensions.

“Our findings suggest that [rituximab] dose interval extension could be considered in patients with RRMS with stable disease without incurring risk of return of inflammatory disease activity in the short to medium term, especially in case of treatment-related adverse events,” the scientists wrote.

The study, “Sustained Low Relapse Rate With Highly Variable B-Cell Repopulation Dynamics With Extended Rituximab Dosing Intervals in Multiple Sclerosis,” was published in the journal Neurology: Neuroimmunology & Neuroinflammation.

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Rituximab Doses for MS Might Be Best Timed By Measuring B-cells

Investigating longer intervals for rituximab treatment in MS

Rituximab is a cancer treatment that helps keep the immune system in check by targeting B-cells — immune cells responsible for making antibodies, including the self-targeting antibodies that contribute to disease in MS. Depleting B-cells is expected to bring down the inflammation that drives nerve cell damage in MS.

The medication, sold as Rituxan in the U.S. and MabThera in Europe, with a number of biosimilars also available, has been used off-label to reduce relapse risk and delay disability progression in MS patients.

But because it works to lower the activity of the immune system, rituximab may increase the risk of adverse immune reactions, such as infections or poor responses to vaccines.

While rituximab treatment is typically given via an infusion into the bloodstream every six months, recent data suggest this interval could be extended to reduce the risk of side effects in MS patients.

Yet, studies with sufficient observation times to determine whether disease outcomes are not impacted by extended dosing are lacking.

To address that, researchers at the Karolinska Institutet and Karolinska University Hospital, in Sweden, examined data from 718 patients included in two observational clinical trials – COMBAT-MS (NCT03193866) and Multiple MS (EudraCT 2017-002634-24). All had received at least two courses of rituximab, which was their first or second disease-modifying therapy.

Participants had been diagnosed at a median age of 32, and had started on rituximab a median of 5.5 years later. Each patient received a median of six rituximab doses, for a total of 4,622 doses.

Excluding the first treatment course, researchers had data for 3,904 dose intervals, gathered over a median follow-up period of 4.2 years. Most intervals were shorter than eight months. The remaining had treatment courses of 8–12 months (15%), 12–18 months (8%), or longer than 18 months (11%).

Importantly, most patients (95%) had at least one dose interval of eight months or longer, and more than half (56%) had at least one gap equal to or greater than 1.5 years (18 months).

Over the follow-up period, a total of 24 relapses were reported, of which 20 occurred within eight months following an infusion. Spacing out the infusions did not increase the risk of having a relapse, the researchers noted. In fact, there was trend toward fewer relapses with extended dosing intervals.

“Overall, these … estimates suggest a similar or lower risk of relapse with transition from a regular to an extended dosing interval regimen,” the team wrote.

The results were similar when considering both relapses and the appearance of new inflammatory lesions, with the extended dosing intervals not increasing the risk of these events.

These findings are in line with a previous study in which the team “reported the absence of rebound disease activity in patients with RRMS who, for various reasons, had stopped rituximab for more than 12 months,” they wrote.

For about 90% of the patients, there were enough data available to track B-cell counts over the follow-up period. B-cell counts varied widely from patient to patient, but close to two-thirds (63.9%) of patients remained with a near-complete reduction over a dose interval shorter than eight months.

In contrast, B-cell counts reached normal levels for most patients in the extended interval groups.

“Dose interval extension could be considered in patients with RRMS with stable disease without incurring risk of return of inflammatory disease activity in the short to medium term,” the researchers concluded.

“Further studies are needed to determine whether dose interval extension is also associated with a lowered risk of infection,” they added.

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