Treatment linked to fewer NMOSD relapses, less steroid use in study
Uplizna was also associated with generally stable disability over one year
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In a real-world study of adults living with neuromyelitis optica spectrum disorder (NMOSD) in Japan, Uplizna (inebilizumab) was linked to fewer relapses, generally stable disability, and less use of corticosteroids.
In addition, the approved therapy’s safety profile was consistent with what had been observed in earlier studies.
“Our findings highlight the utility of [Uplizna] as an effective and well-tolerated treatment option,” the researchers wrote.
Real-world study examines Uplizna use in Japan
The study, “Safety and Effectiveness of Inebilizumab in Patients with Neuromyelitis Optica Spectrum Disorder: Interim Analysis of a Post-marketing Surveillance in Japan,” was published in Neurology and Therapy.
In NMOSD, self-reactive antibodies attack supporting cells of the nervous system, causing inflammation of the spinal cord (myelitis) and the optic nerve, which carries visual information from the eyes to the brain (optic neuritis).
These inflammatory events can cause symptoms to suddenly worsen or new symptoms to appear. These episodes, called relapses, “contribute to irreversible disability, loss of independence, and a marked reduction in quality of life,” the researchers wrote.
NMOSD symptoms, how the disease progresses over time, and how patients respond to treatment can differ widely.
Given as an infusion into a vein, Uplizna works by depleting immune B cells involved in producing antibodies, including self-reactive ones. In the U.S., it is approved to treat adults with NMOSD who test positive for antibodies against the aquaporin-4 (AQP4) protein — the most common target of self-reactive antibodies in NMOSD. In Japan, it is approved to prevent NMOSD relapses.
A subgroup analysis of data from the Phase 2/3 N-MOmentum clinical trial (NCT02200770), whose top-line results supported the therapy’s approvals, indicated that Uplizna was similarly safe and effective in Asian participants.
Because clinical studies have strict eligibility criteria and often exclude patients with comorbidities (other diseases) that are common in everyday practice, the researchers undertook this post-marketing surveillance study to understand how safe and effective the treatment is in a broader group of Japanese patients.
Relapse rates fall as disability remains generally stable
The study included NMOSD patients who started Uplizna after it was approved in Japan. There were 228 patients in the safety analysis and 224 in the effectiveness analysis — three patients were excluded because they continued treatment in the N-MOmentum trial, and another was excluded because anti-AQP4 antibody positivity could not be confirmed.
Patients’ mean age was 54.2 years, most (85.1%) were women, and over two-thirds (68.9%) had at least one comorbidity. The most common symptoms at the time of NMOSD diagnosis were acute myelitis (71.9%) and optic neuritis (51.3%).
Before Uplizna treatment, 33 people (14.7%) had an Expanded Disability Status Scale (EDSS) score of 7 or higher, indicating severe walking disability and essentially meaning they were restricted to a wheelchair. Also, most (92%) were receiving glucocorticoids, a type of anti-inflammatory and immunosuppressive medication, and 31.7% were also on other immunosuppressants.
Patients received a median of four infusions of Uplizna over a median of 379 days (just over one year). Twenty-one patients (9.2%) stopped treatment, with reasons including adverse events, insufficient response, changing hospitals, personal preference, or changing to another therapy.
One measure of effectiveness was the annualized relapse rate (ARR), which reflects the number of relapses per patient-year. ARR fell from 0.40 relapses per patient-year during the two years before Uplizna treatment to 0.10 after treatment began. Twenty people (8.9%) experienced at least one relapse during treatment.
Among patients with available EDSS data, the mean score was 4.26 when treatment started. On this scale, higher scores indicate greater disability. The mean score decreased to 3.8 after six months and 3.74 after one year of treatment with Uplizna.
Steroid use drops during Uplizna treatment
Use of corticosteroids also decreased during Uplizna treatment. Long-term corticosteroid use is associated with complications such as high blood sugar, high blood pressure, and osteoporosis. On average, the daily dose of oral corticosteroids dropped from 11.7 mg before Uplizna to 4.3 mg after one year on the therapy. The proportion of patients taking no oral corticosteroids increased from 8% to 37.5%.
“The ARR was lower after [Uplizna] initiation compared with the 2 years prior to treatment, and the majority of patients remained relapse-free during treatment period,” the researchers wrote. “Additionally, [simultaneous] use of oral glucocorticoids and immunosuppressive therapies decreased over the course of [Uplizna] treatment.”
Adverse drug reactions were reported in 74 patients (32.5%), including serious reactions in 31 (13.6%). In five patients (2.2%), adverse drug reactions led to treatment discontinuation.
Infections were the most commonly reported adverse drug reaction (14.5%), followed by infusion-related reactions (9.2%). One patient died from interstitial lung disease and another experienced sudden cardiac death. Overall, the safety profile was consistent with previous studies. The researchers noted that “the absence of a control group prevents direct comparisons and limits causal inferences regarding the safety and effectiveness of [Uplizna].”
“Treatment was generally well tolerated, with no new safety concerns identified,” the researchers wrote. “As the 6-year surveillance period continues, further data will clarify the long-term safety and sustained effectiveness of [Uplizna] in Japanese patients with NMOSD.”
The study was funded by Tanabe Pharma, and six of its authors are employees of the company.
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