Approved NMOSD therapies better than rituximab at preventing relapses
Study: They also have fewer side effects than off-label medications
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Therapies specifically approved by the U.S. Food and Drug Administration (FDA) for neuromyelitis optica spectrum disorder (NMOSD) are superior to rituximab and other off-label medications at preventing relapses and serious side effects, according to a real-world study in the U.S.
The study also showed that among FDA-approved therapies, the C5 inhibitors Soliris (eculizumab) and Ultomiris (ravulizumab) performed best relative to rituximab.
“FDA-approved disease-modifying therapies are associated with lower relapse rates and fewer serious adverse events compared with rituximab,” researchers wrote.
The study, “Real-World Efficacy and Safety of Neuromyelitis Optica Spectrum Disorder Disease-Modifying Treatments,” was published in Neuroimmunology & Neuroinflammation. It was funded by Alexion, AstraZeneca Rare Disease, which markets Soliris and Ultomiris.
NMOSD relapse prevention has relied on off-label treatments
NMOSD is an autoimmune disease that mainly affects the optic (eye) nerves and the spinal cord. Inflammation in these areas can cause symptoms such as nerve pain and, over time, lead to disability. Preventing relapses, periods when symptoms worsen suddenly or new ones appear, with effective and safe treatments is key to reducing long-term disability.
“Historically, NMOSD relapse prevention has relied on various off-label treatment approaches,” with rituximab (sold as Rituxan and MabThera, with biosimilars available) “as a preferred option in clinical practice, ”the researchers wrote.
Rituximab works by killing B-cells, the immune cells that produce self-reactive antibodies that drive the inflammatory attacks in most NMOSD patients. Mycophenolate mofetil and azathioprine, broader immunosuppressive treatments, are also used off-label for NMOSD, but they carry associated risks of cancers.
In the past seven years, several disease-modifying therapies have been approved for NMOSD in the U.S. These include Soliris and Ultomiris, which both block an immune protein called C5 that contributes to the inflammatory attacks in NMOSD; Uplizna (inebilizumab), which targets B-cells; and Enspryng (satralizumab), which suppresses a pro-inflammatory signaling protein involved in NMOSD.
“Few publications have explored the comparative efficacy of NMOSD therapies,” the researchers wrote.
C5 inhibitor treatment associated with 88% lower relapse risk
In this study, a team of researchers at Harvard Medical School’s Mass General Brigham set out to compare the efficacy and safety of FDA-approved therapies with those of rituximab and other off-label therapies in people with NMOSD.
The study’s main goals were to measure relapse-free survival, which is the time a patient goes without a relapse, and the annualized relapse rate, or the average number of relapses per year. The researchers also looked at safety by tracking serious infections and treatment-limiting side effects. Data on Soliris and Ultomiris were analyzed together as C5 inhibitors.
Data came from 176 patients of the Mass General Brigham hospital network between 2000 and mid-2024. Most were female (83%), and the median age at the first NMOSD attack was 42. Most (86%) had self-reactive antibodies against aquaporin-4, the most common type of NMOSD-driving antibody.
A total of 691 relapses occurred during a median follow-up period of nine years. The most common symptoms during a relapse were related to spinal cord inflammation (46%) and optic nerve inflammation (29%).
Compared with rituximab, treatment with C5 inhibitors was significantly associated with an 88% lower risk of relapse. Treatment with Uplizna and Enspryng also significantly reduced the risk of relapse by 78% and 81%, respectively, relative to rituximab.
This study provides insights into the comparative effectiveness and safety of NMOSD treatments in a real-world setting. In jurisdictions where other treatments are available, we caution against using rituximab first-line in NMOSD.
At five years, 70% of patients treated with rituximab were estimated to be free of relapses, compared with 100% of those in the C5 inhibitor, Uplizna, and Enspryng groups. This proportion was much lower for patients treated with MMF (51%) and azathioprine (35%).
In addition, annualized relapse rates were zero for C5 inhibitors, Uplizna, and Enspryng, and 0.08 for rituximab, 0.19 for MMF, and 0.34 for azathioprine.
Safety analysis showed that rituximab was associated with serious infections in 28% of treatment periods and mild infections in 34%. C5 inhibitors had a significantly lower rate of serious infections compared with rituximab.
Combining effectiveness and safety, C5 inhibitors had the best overall outcomes, while azathioprine and MMF showed a higher combined risk of relapse, serious infections, or intolerable side effects.
“This study provides insights into the comparative effectiveness and safety of NMOSD treatments in a real-world setting,” the researchers wrote. “In jurisdictions where other treatments are available, we caution against using rituximab first-line in NMOSD. We also recommend against the use of MMF and azathioprine.”
