Study: Low Rituximab Dose Effective in Preventing Relapses in NMOSD

Treatment over 3 weeks also found to reduce disability progression

Patricia Inacio, PhD avatar

by Patricia Inacio, PhD |

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A low dose of rituximab — infused at 100 mg weekly for three consecutive weeks — was effective at preventing relapses and disability progression in people with neuromyelitis optica spectrum disorder (NMOSD), according to a meta-analysis of five different regimens.

Moreover, treatment with rituximab at this low dose posed little risk of serious adverse events (side effects), the analysis found.

“In terms of safety, we compared and summarised the adverse events (AEs) and SAEs [serious adverse events] from 17 studies,” the researchers wrote.

“This meta-analysis combined safety, efficacy, and cost, which suggest that 100mg [per week] for 3 consecutive weeks may be the suitable dose of rituximab for patients of NMOSD with a low risk of adverse events,” the team wrote.

The study “Different doses of Rituximab for the therapy of Neuromyelitis optica spectrum disorder: A systematic review and meta-analysis” was published in the journal Multiple Sclerosis and Related Disorders.

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Study: Rituximab Better Than MMF, Azathioprine in Preventing Relapses

NMOSD is caused by an overactive immune system that produces self-reactive antibodies, or autoantibodies, against certain cells of the nervous system. This causes damage to the spinal cord and the optic nerve, which carries messages from the eye to the brain.

Individuals with NMOSD have periodic episodes (relapses) of immune activation, which can result in permanent neurological damages. Delaying or preventing disease attacks is a main focus of NMOSD treatment.

Investigating low-dose rituximab

The cancer treatment rituximab (sold as Rituxan, among others) is commonly used off-label in NMOSD. Given as an intravenous (into-the-vein) infusion, it was been shown to have higher efficacy at preventing relapses than azathioprine and mycophenolate mofetil (MMF, sold as CellCept).

However, “the optimal [rituximab] dose regimen remains a key issue and there is still considerable controversy regarding its dose,” the team of researchers, from China, wrote in their study, noting that dosing regimens “remain controversial due to [the therapy’s] high price and possible adverse events.”

To shed light on the safety and efficacy of different rituximab doses, the researchers conducted a meta-analysis of studies published across four different platforms — Pubmed, Embase, the Cochrane Library, and Clinicaltrials.gov — up until March of this year.

From an initial hit of 2,269 studies, the team included 17 in the final analysis. Altogether, the studies involved 576 patients and five dosage regimens. The doses were: 100 mg per week (mg/w) for three consecutive weeks; 500 mg/w for four weeks; 1,000 mg twice, given two weeks apart; 375 mg per square meter of body surface area (mg/m2) every week for four weeks; and 375 mg/m2, administered once.

Efficacy was assessed by comparing changes in the annual recurrence rate (ARR) — the number of disease recurrences per year — expanded disability status scale (EDSS) scores, and the number of patients free of relapse before and after treatment with rituximab. A relapse was defined as worsening of neurological deficits, lasting for more than 24 hours, in the absence of other potential causes, and occurring more than 30 days after a previous attack. On the EDSS, higher scores reflect greater disability.

The analysis revealed that all doses significantly reduced the relapse rate. In addition, both 100 mg/w for three weeks and 1,000 mg twice, two weeks apart, were more efficacious regimens at significantly reducing EDSS than 500 mg/w for four weeks.

In contrast, 375 mg/m2 given once, and 375 mg/m2 weekly for four weeks, led to no statistically significant improvement in disability rates compared with pre-treatment.

Common adverse events included allergies, rash, itchy skin, infections, and other infusion reactions.

While the higher dose of 1,000 mg was effective at reducing ARR and EDSS, it was linked with more serious adverse events, including worse side effects, and high costs. Those findings make that dose “less likely to be selected,” the team wrote.

Overall, rituximab administered at 100 mg intravenous infusion per week for three consecutive weeks was “significantly effective in reducing ARR and disability rates, with a lower financial burden on patients or the public health system, and a lower risk of adverse events than other doses,” the scientists wrote.

This regimen also led to a significant increase in the number of patients who were relapse-free without serious adverse events, the team noted.

“We are looking forward to more studies related to rituximab so that it may have a promising future in the therapy strategy of NMOSD,” they concluded.