‘Double-positive’ NMOSD patient safely treated with ofatumumab

In rare case, woman positive for antibodies against AQP4 protein and MOG

Patricia Inacio, PhD avatar

by Patricia Inacio, PhD |

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A rare case of neuromyelitis optica spectrum disorder (NMOSD) in a patient positive for antibodies against both aquaporin-4 (AQP4) protein and the myelin oligodendrocyte glycoprotein (MOG) was successfully treated with ofatumumab, a B-cell depleting medication approved for multiple sclerosis (MS), a case study reported.

According to its researchers, this case represents the third published incidence of a “double-positive” NMOSD patient, and it is the first to report ofatumumab’s safe and effective use in such a patient after an initial disease attack.

It also adds to a few other reports supporting the use of ofatumumab in NMOSD patients, given its overall better safety profile relative to rituximab, a therapy promoting the death of antibody-producing B-cells that is often used off-label with NMOSD.

The case study, “The case report of AQP4 and MOG IgG double positive NMOSD treated with subcutaneous Ofatumumab,” was published in the Journal of Neuroimmunology.

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Ofatumumab, like rituximab, targets antibody-producing B-cells

In NMOSD, the immune system wrongly produces antibodies that attack proteins in cells that support the nervous system. About 80% of patients have high levels of antibodies against the AQP4 protein — a diagnostic hallmark of NMOSD. Patients negative for anti-AQP4 antibodies often carry antibodies against MOG.

Since the presence of antibodies against both AQP4 and MOG is extremely rare, disease features in these so-called “double-positive” NMOSD patients remain poorly characterized.

In AQP4-positive NMOSD patients, rituximab is often used off-label as a first-line therapy to control the disease. Marketed as Rituxan in the U.S. and MabThera in Europe, with biosimilars available, it is a first-generation antibody that works by binding to and blocking CD20, a protein on the surface of immune B-cells, leading to their death.

B-cells are the immune cells responsible for producing antibodies, including the self-targeting antibodies that drive autoimmunity in conditions like NMOSD and MS.

However, the use of rituximab, administered directly into the bloodstream (intravenous injection), is often limited due to the risk of whole-body allergic reactions and infections.

Ofatumumab, a second-generation anti-CD20 antibody sold by Novartis as Kesimpta and approved for adults with relapsing forms of MS, shows a more favorable safety profile and comparable efficacy in MS patients. The therapy is given through under-the-skin injections.

Researchers in China described the case of a “double-positive” NMOSD patient successfully treated with ofatumumab.

The woman, 36, was admitted to the hospital after 15 days of reduced visual acuity in the left eye, eye pain, and headache without fever or trauma. She complained of blurred vision, but a brain MRI given at symptom onset showed no definite abnormality.

Over the following five days, her visual acuity worsened leading to vision loss in the left eye. Physicians suspected inflammation of the optic nerve, a hallmark of NMOSD. The optic nerve relays information between the eye and the brain.

She was treated with the standard anti-inflammatory methylprednisolone, a steroid administered intravenously, but no improvement was observed.

Physical examination revealed blindness and impaired light reflexes in the left eye. The activity of the muscles that control eye movements, as well as of the cranial nerves involved in facial movements that include blinking the eyes, were normal.

Her muscle strength, reflexes, and sensation were normal, as was her walking ability. Other physical examination parameters were unremarkable.

Blood work, including for the presence of self-reacting antibodies associated with certain autoimmune diseases, was normal. However, NMOSD-specific antibody tests revealed she was positive for anti-AQP4 antibodies, and to a lesser extent, anti-MOG antibodies.

Patient refused rituximab due to risk of allergic reactions

A brain and spinal MRI detected swelling in the left optic nerve, with additional tests confirming impaired vision in the left eye.

She was diagnosed with AQP4- and MOG-positive NMOSD, presenting moderate disability, as assessed with the Expanded Disability Status Scale.

The woman was given intravenous methylprednisolone for five days at a dose of 1,000 mg/day, followed by oral tapering. Her eye pain and headache resolved, but poor visual acuity in the left eye remained.

Physicians suggested treatment with rituximab to prevent further relapses, but the patient refused due to the risk of allergic reactions and infections. As such, ofatumumab “was chosen due to better tolerance and limited access to hospitalization in the era of the COVID-19 epidemic,” the researchers wrote.

She received ofatumumab at its recommended regimen: 20 mg once weekly for the first three weeks, followed by 20 mg every four weeks.

After four weeks of treatment, during which oral steroids were tapered, visual acuity in her left eye had recovered to 80% and her B-cell counts showed effective depletion.

At a three-month follow-up, visual acuity in the left eye had been restored, but she remained positive for both anti-AQP4 and anti-MOG antibodies, with no changes in their levels.

A brain MRI four months after starting ofatumumab still showed signs indicative of left optic nerve inflammation. But at the most recent follow-up, there were no signs of disease activity, and no adverse events had been reported.

Overall, “we reported a rare case of … double positive NMOSD, who were effectively treated with steroids and OFA [ofatumumab] with a well safety profile,” the researchers wrote, adding that “timely and efficient treatment is crucial for [a] good prognosis.”

Ofatumumab as a “first-line” therapy allowed for “a great recovery” in this woman, they added, noting that further research comparing ofatumumab and rituximab in NMOSD patients is needed.