NMOSD Outcome Not Linked to AQP4 Antibodies at Diagnosis: Study

Corticosteroid, immunosuppressive treatments credited with reducing disability

Patricia Inacio, PhD avatar

by Patricia Inacio, PhD |

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Being positive for or showing high levels of antibodies against the aquaporin-4 (AQP4) protein at diagnosis doesn’t predict worse outcomes for people with neuromyelitis optica spectrum disorder (NMOSD), according to a small study.

Plasma exchange therapy was linked with a trend for slower disability progression, although it wasn’t statistically significant. Also, contrary to prior studies, less than half the patients showed worsening disability over time, likely the result of treatment with high-dose corticosteroids following flares and immunosuppressive maintenance therapies, the scientists noted.

“Our results suggest that patients with NMOSD may not necessarily accumulate disability and may exhibit remission of residual disability between relapses when diagnosed early in the course and started on high efficacy therapy,” the researchers wrote.

The study, “Neuromyelitis Optica: Clinical Course and Potential Prognostic Indicators,” was published in Multiple Sclerosis and Related Disorders.

NMOSD happens when the immune system erroneously attacks cells in the nervous system, leading to the loss of myelin, a fatty sheath protecting nerve cells, and damage to the spinal cord and optic nerves.

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About 70% of NMOSD patients have antibodies against AQP4, a protein that transports water across the membrane of astrocytes, cells of the central nervous system (brain and spinal cord) that support nerve cells.

While previous studies suggested anti-AQP4 antibody levels may serve as a biomarker for the risk of relapse and long-term outcomes, this remains a matter of debate.

“No reliable predictors of acute NMOSD exacerbation [worsening of symptoms] have been identified,” the researchers wrote. “Isolating such a predictor would allow clinicians to escalate therapy in patients with greater risk of relapse.”

To assess the potential of anti-AQP4 antibody levels to predict disability accumulation in NMOSD, researchers at Duke University conducted a retrospective analysis of 53 patients (mean age, 42.79; 77.4% women) with a confirmed NMOSD diagnosis. They were diagnosed at the Duke University Hospital between Jan. 1, 2000, and Jan. 1, 2021.

Six patients were excluded due to insufficient data. Most were treated with high-dose corticosteroids during acute flares and received maintenance immunosuppressive therapies.

Changes in NMOSD disability

Disability worsened in 19 patients (40.4%), but lessened over time in 13 others (27.7%). No changes in disability were seen in 15 patients (31.9%). A total of eight patients died during follow-up at a median age of 63.6 and after a mean disease duration of 1.1 years.

Disability data during the first year of presentation — as measured with the expanded disability status scale (EDSS) — was available from 25 patients among the 29 with transverse myelitis, an inflamed spinal cord. Ten required a wheelchair at the end of the first year.

In 10 cases, disability continued to worsen, while in 10 other cases it eased, an analysis of 27 patients showed. The remaining seven patients showed no disability changes.

Twelve of 13 patients with optic neuritis (inflammation of the optic nerve) as the predominant symptom had asymmetric vision loss, with one eye worse than the other.

Regarding the worse eye, eight patients were legally blind (defined as 20/200 vision or worse) at the end of the first year and nine were legally blind at the last follow-up. Worsening disability over time was seen in six of 12 patients (50%), while disability eased in two.

No reliable predictors of acute NMOSD exacerbation [worsening of symptoms] have been identified. Isolating such a predictor would allow clinicians to escalate therapy in patients with greater risk of relapse.

As for the better eye, one of nine patients with one-year data was legally blind. In most patients (75%), disability continued to worsen and in two cases (16.7%) it lessened.

No link between disability, antibody level

No significant link was found between worsening disability and high blood levels of anti-AQP4 antibody, or between a positive versus negative test for these antibodies.

These findings “failed to support an association between clinical prognosis and AQP4 seropositivity or AQP4 serum [blood] titer levels,” the researchers wrote.

They next assessed how plasma exchange (plasmapheresis), which involves replacing a person’s plasma with a plasma substitute impacted disability progression. Again, no significant association was found. Plasma is the noncellular part of blood.

“We were unable to find evidence supporting a favorable effect of plasmapheresis administration on disease outcomes,” the researchers said. In fact, those who underwent plasmapheresis within 30 days of symptoms showed “a trend towards better outcomes (slower progression of disability).”

The researchers did acknowledge the small number of patients may have limited their analysis.

“Given the rarity of this condition, sample size has been a common limitation in both our study and prior studies on NMOSD — highlighting the ongoing need for multi-center studies on this condition and the development of multi-center databases of NMOSD data,” the study concluded.