MRI of patient with Neuromyelitis Optica Credit: Frank Gaillard
Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune condition that affects the optic nerves and spinal cord, leading to relapses that can cause blindness or paralysis. The N-MOmentum study examined Uplizna (inebilizumab-cdon), a targeted therapy developed by Viela Bio, now part of Horizon Therapeutics and marketed by Amgen. Published in CNS Drugs in September 2022, the study focused on adults with the anti-aquaporin-4 (AQP4) antibody. The U.S. Food and Drug Administration (FDA) approved Uplizna on June 11, 2020, after clinical evidence demonstrated its ability to reduce the frequency of NMOSD attacks. However, some patient groups remain unstudied, leaving key questions unanswered.
N-MOmentum Study Overview
The N-MOmentum trial enrolled 230 adults diagnosed with NMOSD across multiple global centers. Participants had an average age of 43, and 213 tested positive for the AQP4 antibody, a biomarker present in 76% of NMOSD cases.
The study randomly assigned patients to one of two groups:
Treatment group (n=174): Received 300 mg of Uplizna intravenously on days 1 and 15.
Placebo group (n=56): Received a matching placebo on the same schedule.
The trial was halted early due to strong efficacy signals, confirming Uplizna’s benefit in reducing attack risk.
Key Findings: Reduced Attack Risk
Among AQP4-positive patients (n=161), Uplizna demonstrated a 77% reduction in relapse risk compared to placebo.
Attack rates:
12% of patients on Uplizna experienced an attack.
39% of patients on placebo had an attack.
AQP4-positive subgroup:
11% on Uplizna relapsed versus 42% on placebo.
Long-term follow-up (four years):
Attack rates declined to 0.052 per year, approximately 5%.
87% of patients remained relapse-free after the first year.
These findings confirm that Uplizna significantly reduces NMOSD relapses, potentially lowering the risk of severe disability over time.
Additional Benefits Beyond Relapse Prevention
Beyond attack reduction, Uplizna also demonstrated benefits in preventing disease progression:
Disability worsening (Expanded Disability Status Scale):
16% of patients on Uplizna experienced worsening disability compared to 34% on placebo—a 63% lower risk.
MRI analysis:
43% reduction in new or enlarging lesions (1.6 lesions vs. 2.3 in placebo).
Hospitalization rates:
Hospital stays decreased by 71%, from an average of 1.4 to 1.0 per patient.
Over the four-year study period, disability scores remained stable in the Uplizna-treated group, further supporting its role in disease management.
Treatment Schedule and Patient Considerations
Uplizna is administered via intravenous infusion:
Loading doses: Two 90-minute infusions given two weeks apart.
Maintenance: One infusion every six months.
This schedule offers a less frequent treatment option compared to some alternative therapies, which require more frequent dosing.
Risks and Side Effects
As with other B-cell-depleting therapies, Uplizna carries certain risks. In the N-MOmentum study, side effects occurred in both treatment and placebo groups at similar rates.
Common adverse events (over 6.5 months):
Urinary tract infections: 11%
Joint pain (arthralgia): 10%
Headaches and upper respiratory infections: 7% each
Serious adverse events:
5% of Uplizna-treated patients versus 9% in the placebo group.
Over four years, 90% of patients reported side effects, with infections occurring in 79%, though most were mild. Three deaths were recorded, one of which was possibly linked to treatment. Low antibody levels (hypogammaglobulinemia) affected 53% of patients, with 3% experiencing severe cases requiring clinical management.
Contraindications and Warnings:
Pregnancy: Uplizna is contraindicated due to potential fetal harm. Women should use contraception during treatment and for six months after the last dose.
Infections: Patients must be screened for hepatitis B and tuberculosis before starting treatment.
Vaccinations: Live vaccines should be administered at least four weeks before starting Uplizna.
Unanswered Questions from the Study
While Uplizna is effective for AQP4-positive NMOSD, several key questions remain:
Can Uplizna Benefit AQP4-Negative Patients?
The study included only 17 AQP4-negative patients. Among them:
Uplizna group (n=13): 3 patients relapsed.
Placebo group (n=4): No relapses occurred.
With such a small sample, the results are inconclusive. Further research is needed to determine whether Uplizna is effective in AQP4-negative NMOSD, which affects about 24% of patients.
Does Uplizna Improve Vision Recovery?
NMOSD relapses often cause optic neuritis, leading to permanent vision loss. While the trial demonstrated attack prevention, it did not assess improvements in visual function:
Low-contrast vision scores remained unchanged (1.576 vs. 1.442).
Future studies should explore whether early intervention with Uplizna preserves or restores vision.
What About Pediatric and Pregnant Patients?
Pregnant and breastfeeding women were excluded from the study, despite 91% of NMOSD patients being female.
Children with NMOSD, who often experience severe disease, were not studied.
Without data, it remains unknown whether Uplizna is safe for pregnancy or pediatric use.
Does Uplizna Address Chronic Pain?
Up to 80% of NMOSD patients experience chronic pain, as reported in (Bradl et al., 2014).
The trial did not evaluate Uplizna’s impact on long-term pain management.
Future studies could examine whether Uplizna helps alleviate chronic symptoms beyond attack prevention.
Comparing Uplizna to Prior Treatments
Before Uplizna’s approval, NMOSD patients relied on off-label rituximab, which showed relapse-free rates of 30% to 80%. The N-MOmentum study’s 77% relapse reduction aligns with the highest rates seen in prior treatments.
Compared to eculizumab and satralizumab, Uplizna offers:
✔ Comparable or better attack prevention
✔ Greater disability protection
✔ Less frequent dosing (every six months vs. biweekly or monthly infusions)
Long-Term Implications and Future Research
Repeated NMOSD attacks lead to cumulative disability, as highlighted in Neurology (2015). Each relapse increases the risk of permanent damage. The N-MOmentum study’s drop from 39% to 12% relapse rates suggests Uplizna provides a crucial layer of protection for patients with AQP4-positive NMOSD.
Final Thoughts
The N-MOmentum study proves Uplizna cuts relapses and stabilizes disability for AQP4-positive adults, yet gaps remain that matter to patients and families. Only 17 AQP4-negative patients were tested, with 3 of 13 relapsing, so efficacy for the 24% of NMOSD patients without AQP4 antibodies stays unclear. Ask your doctor if there are any clinical trials exploring this group. Over four years, 79% of patients faced infections because Uplizna affects immune cells that fight germs. Discuss monitoring options, such as regular blood tests, to catch issues early. Vision didn’t improve, with scores steady at 1.576 versus 1.442, meaning no gain in blurry sight despite fewer attacks. Talk to an eye specialist about vision rehab if optic neuritis lingers. Chronic pain, often burning or numbness, affects up to 80% of NMOSD patients (Bradl et al., 2014), but wasn’t studied. Ask about pain relief, like physical therapy or medications, to ease daily discomfort. No data exists for kids or pregnant women, despite 91% of patients being female. Caregivers can check with pediatric neurologists for trials, some underway at places like the NIH, while women planning pregnancy should explore alternatives with their doctor. These steps turn unknowns into action, helping patients, caregivers, and families manage NMOSD beyond relapse prevention.
Reference
Nie, T., & Blair, H. A. (2022). Inebilizumab: A review in neuromyelitis optica spectrum disorder. CNS Drugs, 36(10), 1133–1141. https://doi.org/10.1007/s40263-022-00949-7
Bradl, M., Kanamori, Y., Nakashima, I., Misu, T., Fujihara, K., Lassmann, H., & Sandkühler, J. (2014). Pain in neuromyelitis optica—prevalence, pathogenesis and therapy. Nature Reviews Neurology, 10(9), 529–536. https://doi.org/10.1038/nrneurol.2014.129