Analysis: First-line Rituximab Better Than MMF at Preventing Relapses

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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Rituximab may be a more effective immunosuppressive therapy for preventing a first relapse in people with neuromyelitis optica spectrum disorder (NMOSD) than mycophenolate mofetil (MMF), a new meta-analysis found.

The anti-CD20 antibody rituximab, commonly used off-label in NMOSD, also appears to work better than azathioprine, though the results failed to reach statistical significance.

“These results aim to help future first-line treatment strategies,” the investigators wrote.

The study, “A meta-analysis comparing first-line immunosuppressants in neuromyelitis optica,” was published in the Annals of Clinical and Translational Neurology.

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Several immunosuppressants and monoclonal antibodies have been used to reduce the rate of relapses in NMOSD. These therapies work to suppress the body’s immune system, thereby reducing the immune attacks that damage the spinal cord and optic nerve in NMOSD.

Some of the most commonly recommended first-line therapies are rituximab (sold as Rituxan among others), MMF (sold as CellCept and other medicines), and azathioprine. However, it remains unclear which of these are more effective at preventing relapses in NMOSD patients.

To shed light on this, an international team of researchers investigated published studies that compared at least two of these medications as a first-line treatment for NMOSD. The team identified 13 studies, of which only seven were considered to have sufficient data for analysis.

The studies were published from 2016 to 2020, and included data from 919 patients — of whom 232 (25%) were treated with rituximab, 294 (32%) with MMF, and 393 (43%) with azathioprine. The majority of these patients (83.9%) tested positive for autoantibodies against the aquaporin-4 (AQP4) water channel — the main cause of NMOSD.

Overall, the studies had very good quality in their design, with a low risk of bias. A total of five studies enabled a comparison between rituximab and MMF, while five studies compared rituximab with azathioprine. All seven had comparisons between MMF and azathioprine.

The main goal of this analysis was to determine which treatment was more effective in delaying a first relapse.

Results showed that patients on MMF had a significantly greater risk — 55% higher — of experiencing a first relapse than those on rituximab.

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For azathioprine, the results were less clear, as there were no significant differences between rituximab and azathioprine, and between MMF and azathioprine. Of note, the risk of first relapse was 42% higher for patients on azathioprine compared with rituximab, but the differences were not statistically significant.

Of note, additional analyses demonstrated that factors such as the presence of AQP4 antibodies, age, sex, the rate of relapse, and the additional use of the corticosteroid prednisone did not have a significant impact on the treatments’ effects.

“The results of this updated systematic review and meta-analysis of the most widely used immunosuppressants in first-line strategies … suggest that RTX [rituximab] is more efficient than MMF in delaying relapses,” the researchers wrote.

The researchers noted that the lack of individual data from each patient prevented them from adjusting their findings for potential factors that could impact treatment efficacy. Nevertheless, they noted that “the observed effect difference between both treatments combined with the results of previous studies using [a different outcome measure] may be in favor of RTX.”

Further study still is needed, the team noted, adding that “recommendations in the management of … NMOSD are still not updated and remain to be discussed.”