5 Years on Immunosuppressants May Reduce NMOSD Relapse Risk by 50%

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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Longer-term treatment with immunosuppressants may halve the risk of relapse, or of symptoms returning, in neuromyelitis optica spectrum disorder (NMOSD), a study in China found.

When taken non-stop for up to five years, such treatment reduced the risk of relapse in NMOSD patients, with a mild rebound when immunosuppressants were taken for longer periods of time.

Moreover, the cancer therapy rituximab, when used off-label for up to three years, nearly zeroed the risk of relapse, and delayed the return of NMOSD symptoms, even after no longer being taken, data showed.

The researchers noted that while long-term treatment with immunosuppressants is mostly acceptable, toning down or stopping rituximab after at least three years of treatment “may be a strategy worth trying.”

The study, “Immunosuppressant and neuromyelitis optica spectrum disorder: optimal treatment duration and risk of discontinuation,” was published in the European Journal of Neurology.

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Analysis: First-line Rituximab Better Than MMF at Preventing Relapses

NMOSD is caused by an overactive immune system that turns against some of the cells in the body’s nervous system. This causes damage to the spinal cord and the optic nerve, which carries messages from the eye to the brain.

Immunosuppressants work by calming down the immune system. But while they are sometimes used to prevent NMOSD from recurring, it is unclear how long treatment should last.

Some doctors recommend taking immunosuppressants for at least five years, and others for a lifetime. Others still recommend stopping treatment as soon as patients seem to have reached a stable condition. However, stopping treatment can cause more attacks to follow.

Determining the optimal length of treatment

To help define the optimal treatment duration — and how to best use immunosuppressants to reduce the risk of relapse — a team of researchers from the Third Affiliated Hospital of Sun Yat-sen University, in China, drew on a database of nearly 700 patients with NMOSD in the southern part of the country.

A total of 343 of these patients were on immunosuppressants. NMOSD is more common in women than in men, and almost all (93.3%) of the patients in the study were female.

Symptoms first started when these patients were a median of 35 years old, and their disease duration was a median of 73 months, or just over six years. Some 56 patients (16.3%) had a coexisting autoimmune disease. An unidentified number of patients were treated with more than one therapy.

Azathioprine, given as a tablet, was used by 202 patients (58.9%) for a median of 32 months. Meanwhile, mycophenolate mofetil, sold as CellCept, was taken by 178 people (51.9%).

Rituximab — approved in the U.S. and other countries to treat certain blood cancers and some autoimmune diseases — was used by 32 patients (9.3%) for a median of 15.5 months. A monoclonal antibody, Rituxan is sold as Rituxan and other brand names.

The results showed that a longer treatment duration cut by nearly half the risk of relapse — defined as a new attack occurring more than one month after the previous one and lasting for more than one day.

The immunosuppressants reduced the risk of relapse when taken for up to five years, with a mild rebound starting from there on. The team hypothesized that this happened because patients may experience periods of “clustered” attacks spaced by periods of sparse relapses, as indicated by previous research.

For doctors, this may mean that immunosuppressants “cannot be stopped without caution because it cannot be predicted when the patient will enter the ‘clustered attack’ period in the future.”

Rituximab brought the risk of relapse down to nearly zero within three years.

Among the patients, 129 (37.6%) stopped taking their immunosuppressants after a median of 15 months, due to a variety of factors. Some decided on their own to do so, others had side effects, still others wanted to get pregnant, and some were told to do so by their doctors when they had no symptoms for more than two years.

Of these 129 individuals, 100 (77.5%) had one or more relapses a median of seven months after they stopped taking their immunosuppressants. For rituximab, this time lag was a median three months longer.

“Future studies should explore individualized strategies of rituximab maintenance treatment,” the researchers wrote, adding that its discontinuation “still needs to be cautious.”

Patients with longitudinal extensive transverse myelitis had double the risk of relapse after they stopped taking their immunosuppressants, the data showed. This condition is characterized by an inflammatory lesion of the spinal cord that extends over three or more vertebrae in the backbone.

Since longitudinal extensive transverse myelitis attacks are associated with severe disability and higher relapse risk, “these patients may need long-term high-efficiency [immunosuppressant] treatment (i.e., [rituximab]) more than others,” the researchers wrote.

Further study involving new treatments is needed, the team noted, but added that these findings “will assist physicians in developing clinical strategies and individualized treatment regimens.”