Regular rituximab treatment lessens NMOSD relapses: Real-world data
Low-dose preventive therapy also reduced disability risk in patients in China
Regular maintenance treatment with low-dose rituximab is associated with less disability and fewer relapses among people with neuromyelitis optica spectrum disorder (NMOSD) compared with receiving irregular doses of the preventive therapy, according to a two-year real-world study in China.
“Regular [rituximab] treatment can significantly reduce the annual relapse rate, incidence of severe attacks, and risk of disability in patients with NMOSD,” the researchers wrote, noting that when looking at relapses occurring at least a month after the starting the therapy, more than 80% of patients had experienced none.
These individuals “were relapse-free,” the researchers wrote, further noting that there were no severe side effects reported among patients.
According to the team, “this study underscores the efficacy of low-dose RTX [rituximab] in preventing NMOSD relapse and reducing [disability], providing a reference for future investigations into optimal RTX dosing for NMOSD treatment.”
The study, “A real‑world study on the utility of regular rituximab treatment for neuromyelitis optica spectrum disorder,” was published in the Journal of Neurology.
Researchers note high costs, limited availability of NMOSD therapies in China
NMOSD is an autoimmune condition that results in damaging inflammation in the spinal cord and the nerves that transmit signals between the eyes and the brain. This can lead to difficulties with muscle coordination and vision.
The disease is marked by relapses, when symptoms suddenly worsen, followed by remission phases in which they lessen. Over time, repeated relapses can result in cumulative damage that is associated with severe disability.
In most cases, NMOSD is linked to the presence of self-reactive antibodies targeting AQP4, a protein found on astrocytes, which are supportive, star-shaped cells in the nervous system.
Several therapies have been approved for NMOSD. However, their generally high costs and limited availability in China make rituximab (sold as Rituxan, Mabthera, and others) a more accessible option for many patients.
Rituximab, an immunosuppressive therapy approved for certain cancers and autoimmune diseases, is commonly used off-label in NMOSD to prevent relapses and ease disability. Administered via infusions directly into the bloodstream, it works by eliminating B-cells, the immune cells responsible for producing antibodies.
The problem, the researchers noted, is that “a consensus regarding dosage and maintenance intervals is lacking, and the effects of regular/irregular use on disease recurrence and prognosis, and the risk factors associated with clinical relapse, remain unclear.”
In addition, long-term high-dose rituximab use carries risks, like infections, that are associated with immunosuppression. As such, “measures that can help minimize drug exposure, reduce costs, and ensure treatment efficacy and safety are beneficial,” the researchers wrote.
With this in mind, the research team retrospectively analyzed data from 106 NMOSD patients who were seen at one of two Chinese hospitals and received at least one rituximab infusion.
Their goal was to assess the efficacy and safety of regular versus irregular low-dose rituximab in NMOSD patients. Additionally, the team aimed to identify relapse predictors to help personalize treatment and improve patient outcomes.
The patients’ median age at disease onset was 34.5 years, and most (84.9%) were women. Rituximab was given first as an induction dose, at 500 mg once weekly for two consecutive weeks, followed a maintenance dose of 500 mg every six months. Treatment spanned a median of 28.5 months, or nearly 2.5 years.
Intervals of nine months between rituximab doses, or a single dosing interval of more than 12 months without B-cell monitoring, classified patients as having received irregular treatment. In all others, rituximab treatment was deemed regular.
Regular rituximab treatment leads to fewer relapses for over 90% of patients
The study’s results showed that, in the overall patient population, rituximab treatment was associated with significantly lower median annual relapse rate (ARR) and mean scores on the Expanded Disability Status Scale (EDSS), a measure of functional disability in which lower scores indicate less disability.
NMOSD patients treated regularly with rituximab showed better outcomes than irregular users, including a significantly lower mean EDSS score (3 vs. 3.5), median ARR (0 vs. 0.2), and relapse frequency (median 0 vs. 1). Also, a significantly smaller proportion of patients on regular treatment experienced a severe relapse (15% vs. 42.3%), the data showed.
In the regular rituximab group, 92.5% of patients experienced a significant decrease in ARR, and 63.8% achieved a relapse-free status. Further analyses showed that in these patients, the cumulative risk of relapse after rituximab was significantly lower relative to the period before rituximab.
Also, when considering only relapses occurring more than one month after starting treatment, 82.3% of NMOSD patients testing positive for anti-AQP4 antibodies were relapse-free.
During the initial [two] years of the disease, a regular [rituximab] treatment regimen is crucial for achieving effective disease control and immunosuppression. … Our study results emphasize the urgency and importance of regular [rituximab] treatment during this period.
Statistical models adjusted for potential influencing factors showed that high blood levels of anti-AQP4 antibodies at initial disease onset, and severe demyelinating episodes in the first attack were significantly associated with a twofold higher risk of relapse. Demyelinating episodes are those occuring when myelin, the protective sheath around nerve fibers, is lost.
During the study, 18.9% of patients experienced side effects related to rituximab, mostly occurring during infusion. These adverse effects were mild, temporary, and most commonly involved headaches, seen for 35% of patients, hair loss, affecting 25%, and rash, as seen in 20%. Skin flushing and fatigue were each seen in 10% of those receiving the preventive treatment. Side effects were managed by slowing the infusion rate or using anti-allergic treatments.
Overall, these findings show that “during the initial [two] years of the disease, a regular treatment regimen is crucial for achieving effective disease control and immunosuppression,” the researchers wrote. “Our study results emphasize the urgency and importance of regular RTX treatment during this period, providing valuable insights into early treatment responses and disease stabilization.”
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