Plasma Exchange Benefits Patients With Neuromyelitis Optica

Daniel M. Keller, PhD

June 24, 2014

ISTANBUL, Turkey — A new study suggests that total plasma exchange (TPE) is therapeutic in patients with neuromyelitis optica (NMO) who are refractory to treatment with high-dose corticosteroids. It may also be a useful first-line therapy, researchers say.

The study also provides some clues as to the characteristics of patients who respond best, lead author Ilav Kiliç, MD, Ege University School of Medicine in Izmir, Turkey, told delegates here at the 24th Meeting of the European Neurological Society (ENS).

Dr. Kiliç concluded that TPE "was found to be significantly therapeutic in NMO attacks."

Interrupting Progression

NMO is an autoimmune disorder associated with antibodies to aquaporin-4, which is expressed on optic nerves and the spinal cord. The course of NMO may be a single event or relapsing.

The aim of TPE is to remove antibodies, complement, and cytokines from the blood. Because autoantibodies can persist in the circulation for several weeks, TPE is a way to rapidly remove them and interrupt the progression of lesions faster than is possible with steroids.

However, TPE in general is associated with adverse events of hypotension, pulmonary edema and dyspnea, coagulopathy, infection, catheter-related complications, and citrate-induced hypocalcemia.

In this small retrospective study, the researchers reviewed the medical records of 12 patients with NMO treated with TPE at their institution between March 2011 and October 2013 to determine response rates and characteristics associated with response.

The 12 patients were treated for 14 acute attacks. Of those, 2 patients received 2 series of TPE for 2 different attacks (5 + 5 exchanges and 5 + 1 exchanges each).

Using the criteria of Keegan et al, the researchers graded responses as 0 (no improvement), 1 (mild improvement), 2 (moderate improvement), or 3 (marked improvement). Grades 0 or 1 were considered no or poor response, and grades 2 and 3 as significant response.

Anti-NMO antibodies, measured before plasmapheresis, were present in 9 patients. The mean number of TPE sessions was 5.4 (range, 1 to 10). The mean interval between NMO attack and TPE was 51.6 days (range, 2 to 150 days).

Predictors of Response

Dr. Kiliç reported that 6 of 14 patients (43%) responded to TPE therapy, with statistically significant improvements in their Expanded Disability Status Scale score at 1 (P = .04) and 3 (P = .03) months.

Two of 14 attacks were treated with TPE as first-line therapy, 9 with TPE as second-line therapy after high-dose corticosteroids, and 3 with TPE as third-line therapy after corticosteroids plus immunosuppressants (2 patients) or after corticosteroids and intravenous immunoglobulin (1 patient).

In 8 of 14 attacks, patients had abnormal visual evoked potentials. Two patients presented with quadriparesis, 2 with hemiparesis, and 2 with optic neuritis. Seven patients had elevated protein levels in their cerebrospinal fluid.

Younger age was a predictor of response. The mean ± SD age of responders (Keegan 2 and 3) was 32.75 ± 6.11 years vs 53 ± 6.24 years for nonresponders (Keegan 0 and 1; P = .01).

The mean time interval between attack and TPE was longer for responders (P = .03), which is contrary to the current literature, Dr. Kiliç said, and "using TPE as a first-line therapy was found to be significantly related to a better response [P = .03]," she told the session attendees.

Duration of the disease did not significantly differ between responders and nonresponders (733 vs 709 days, respectively). Only 2 patients improved between the month 1 and month 3 assessments. All others remained stable.

Dr. Kiliç said that TPE was well tolerated among surviving patients. However, 3 patients in the cohort died. All 3 were NMO antibody negative. Two of the patients died of sepsis: 1 woman during her second treatment session and 1 man 2 days after his first session. The third patient died of a myocardial infarction 9 months after TPE, which was thought most likely not to be related to the treatment.

She noted that limitations of the study are its small sample size, that there were only 2 men among the 12 patients, and anti-NMO antibody negativity in only 3 patients, so no comparisons could be done for response based on sex or antibody status. In addition to the 1 patient who died after her first treatment, 3 others were lost to follow-up and therefore not included in the month 3 assessment.

Dr. Kiliç noted that using just 1- and 3-month assessments may be too short of a time period possibly to see further therapeutic benefits. Some other studies have gone out to 6 months.

Although Keegan had found that earlier initiation of plasmapheresis was associated with better outcomes, the results of this study suggest that patients treated more than 60 days after the onset of an attack often experience a favorable response, "and should not be excluded from treatment," she advised. The study also suggests which patients may best be offered TPE for NMO.

Nils Erik Gilhus, MD, professor and head of the Department of Clinical Medicine at the University of Bergen, Norway, and consultant at Haukeland University Hospital, commented on the study to Medscape Medical News. "I think it's promising, but of course, there are weaknesses in the study," he said. "It's not controlled. It's retrospective."

The 2 deaths during the study period concerned Dr. Gilhus. "That has more to do with local patient conditions because you know that plasma exchange is a safe treatment. I mean, it's not a new treatment. It's been done for years, and it's regarded as a safe treatment.

"From what she presented, it could be useful," he added. "And it is also interesting that she tried to identify best responders and finding factors to identify which show this."

There was no commercial funding for the study. Dr. Kiliç and Professor Gilhus have disclosed no relevant financial relationships.

24th Meeting of the European Neurological Society (ENS). Abstract OS2221. Presented June 1, 2014.

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