New data published in The Journal of Neurology, Neurosurgery and Psychiatry offer insights into associated causes behind neuromyelitis optica spectrum disorder (NMOSD) and the impact of Uplizna (inebilizumab-cdon) in managing the condition.
Give me some background on NMOSD first.
NMOSD is a unifying term for neuromyelitis optica (NMO, also known as Devic’s disease) and related syndromes.
These conditions are rare, relapse-prone neuroinflammatory autoimmune diseases of the central nervous system that are typically characterized by attacks of optic neuritis, transverse myelitis, and—on isolated occasions—brain or brainstem inflammation.
Further emphasis on symptomatology for optic neuritis can include:
- Loss or blurring of vision in one or both eyes
- Loss of color vision
- Eye pain
How is it managed?
Disease management is focused on preventing NMOSD-associated attacks by tracking four serum biomarkers.
- Serum neurofilament light chain (sNfL)
- Serum glial fibrillary acidic protein (sGFAP)
- Ubiquitin C-terminal hydrolase L1 (sUCHL1)
- Tau (sTau)
Now talk about Uplinza.
Uplizna is an FDA-approved, CD19-directed cytolytic antibody indicated for the treatment of NMOSD in adults who are anti-aquaporin-4 immunoglobulin G seropositive (AQP4-IgG+), and the only approved treatment that targets B-cells, including plasmablasts and plasma cells (which can contribute to NMOSD).
The medication is administered in two doses of 90-minute intravenous infusions over the course of 2 weeks with an anti-CD19+ (B-cell depletion) mechanism of action.
What are the doses?
The initial dose of 300 mg is followed 2 weeks later by a second dosage of 300 mg.
For any subsequent doses (starting at least 6 months after the first infusion), a single 300 mg infusion is recommended every 6 months.
To note: Each dose is titrated in 250 mL of 0.9% sodium chloride.
See here for the full prescribing information.
Now talk about this trial.
The multicenter, randomized, double-masked, placebo-controlled N-MOmentum study (NCT02200770) assessed the effectiveness of Uplizna in 231 patients over 28 weeks, followed by a 2-year, open-label extension period.
Patients were randomized 3:1 to receive either Uplizna or a matching placebo (300 mg) via intravenous infusions on Day 1 and Day 15 (and then assessed for 12 months). For those in the open-label period (OLP), this was followed by a single dose every 6 months for 3 years.
What was assessed?
Investigators increased the concentration levels of the four serum biomarkers (sNfL, sGFAP, sUCHL1, sTau) associated with NMOSD during the attacks as well as in the days leading up to the attacks.
Which was the strongest?
When measured at the time of the attack, sNfL was the strongest predictor of worsening disability both during and after.
Meaning?
The finding suggests that a higher level of sNfL may be connected to more severe NMOSD attacks as well as an increased risk for residual disability—confirming previous research into the biomarker’s link.
Give me some numbers.
Uplizna-treated patients had significantly lower levels of sNfL (22% above 16 mg/mL) at the end of the study versus the placebo group (45% above 16 mg/mL) as well as lower levels for the other biomarkers.
What about the patients who still experienced attacks?
Lower biomarker levels during the attacks were noted for Uplizna-treated patients compared to placebo-treated.
And those who didn’t?
Horizon reported that sGFAP levels were significantly lower among Uplizna-treated patients versus placebo-treated.
Significance?
According to Kristina Patterson, MD, PhD, Horizon’s senior medical director, neuroimmunology affairs, “The availability of these data in a rare and challenging disease like NMOSD can inform disease management strategies and contribute to improved outcomes for this population over time.”