Neuromyelitis Optica: What Immunosuppressive Agent Is Best?

January 23, 2014

By Megan Brooks

NEW YORK (Reuters Health) Jan 23 - Rituximab and mycophenolate are superior to azathioprine for treatment of neuromyelitis optica (NMO), a comparative analysis shows.

"For a new diagnosis, I would recommend either rituximab or mycophenolate," senior author Dr. Michael Levy, from Johns Hopkins Hospital in Baltimore, Maryland, told Reuters Health.

"Between these two, considerations such as convenience, cost, and adverse effects are important. For patients already on azathioprine, I would not recommend switching unless their disease is not well controlled or the medication is not tolerable," Dr. Levy said.

Effective immunosuppression is the standard of care for preventing relapse in NMO, which affects the optic nerves and spinal cord, leading to blindness and paralysis. But there is no consensus on how to select initial therapy, the investigators noted in a January 20 online paper in JAMA Neurology.

In a retrospective study, they compared relapses and treatment failures in 90 patients with NMO or NMO spectrum disorder who were treated with optimal doses of the three most commonly used immunosuppressive agents for the disease.

They report that rituximab reduced the relapse rate up to 88.2%, with two out of three patients achieving complete remission.

Mycophenolate mofetil cut the relapse rate by up to 87.4%, but had a 36% failure rate.

Azathioprine reduced the relapse rate by 72.1%, but had a failure rate of 53%, despite concurrent use of prednisone.

The researchers say their data on azathioprine in NMO is supported by another study that found a relapse rate of 66% with this drug. In that study, published in 2011 in Neurology, the authors also reported that 22% of patients discontinued azathioprine and 3% developed lymphomas, suggesting that the drug has additional safety risks and tolerability concerns, Dr. Levy and colleagues point out.

They further note that azathioprine therapy for NMO has not been studied without concurrent prednisone, whose adverse effects include hypertension, hyperglycemia, mood disturbances, glaucoma, and bone density loss.

Based on the current study, rituximab is the most effective treatment option for NMO, with the greatest reduction in relapse rate and lowest failure rate, the investigators say.

Importantly, the data also show that patients who fail initial treatment with one of these agents often achieve remission when switched to another, they say.

Among 18 patients who did fail initial treatment with one of the three agents, 14 were successfully switched to mycophenolate or rituximab. Only four patients failed two treatment options, including three patients in whom both mycophenolate and rituximab failed.

For these few patients, "additional options may include experimental immunotherapies with drugs such as cyclophosphamide or methotrexate," the investigators say.

"Recently, eculizumab, a C5a complement inhibitor, minimized disease activity in 12 of 14 NMO patients, most of whom had undergone failed first-line treatment. A phase 3 trial of eculizumab in NMO patients is currently in preparation and may be available to patients for whom standard therapy fails," they add.

The study was supported by the Guthy-Jackson Charitable Foundation. All but one of the authors list conflict of interest disclosures.

SOURCE: http://bit.ly/1jqlZv7

JAMA Neurol 2014.

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