Assistant Professor of Neurology, Weill Cornell Medical College

Dr. Perumal reports she is a consultant for Genzyme and Biogen.

SYNOPSIS: Based on a large study of patients in a national registry, investigators reported similar efficacy when comparing the two apheresis techniques: plasma exchange vs. immunoadsorption for the treatment of relapses in NMOSD. Early initiation of apheresis was associated with better outcomes.

SOURCE: Kleiter I, Gahlen A, Borisow N, et al. Apheresis therapies for NMOSD attacks: A retrospective study of 207 therapeutic intervention. Neurol Neuroimunol Neuroinflamm 2018;5:e504. doi:10.1212/NXI.0000000000000504.

Neuromyelitis optica spectrum disorders (NMOSD) are characterized by attacks of optic neuritis and/or transverse myelitis. The relapses of NMOSD generally are more severe than those in multiple sclerosis and often are refractory of intravenous (IV) steroids. Accumulation of disability in NMOSD tends to occur from residual deficits from relapses rather than from a progressive disease course. Hence, prevention of and optimal treatments for relapses are of utmost importance in decreasing the accrual of long-term disability. Apheresis is used frequently to treat NMOSD relapses refractory to IV steroids or even as the first-line treatment. Kleiter et al sought to compare plasma exchange (PE) vs. immunoadsorption (IA) to determine if one technique was superior to the other.

The analysis included 207 relapses that occurred in 105 NMOSD patients. Data collected in the German registry of NMOSD patients (NEMOS database) were reviewed. Apheresis treatment was used as first-line therapy in 72 instances, second-line therapy in 98, and third-line or later in 37. In the study, 192 relapses were treated with PE and 38 with IA. Median time to initiation of apheresis was one day when it was the first treatment, 11.5 days when it was the second treatment, and 15.5 days when it was the third treatment. Apheresis treatment had to be at least three
sessions.

The outcome measure was recovery from the relapse measured immediately after completion of therapy. The results were categorized as complete recovery, partial recovery, and no recovery.

Both PE and IA were equally effective for treating NMOSD relapses. Patients had at least partial recovery with the use of either apheresis therapy. Forty percent of patients achieved complete recovery when apheresis was started within days 0-2 of symptom onset; after that, treatment response declined in a stepwise manner with longer duration to treatment initiation. No patient achieved complete recovery when apheresis was started 20 days or more after symptom onset.

The strongest predictors of response to treatment were the use of apheresis as the initial treatment for the relapse, the time to treatment from symptom onset, and the presence of aquaporin-4 antibodies. Monofocal relapses were more likely to have a better response when compared to multifocal ones, and a younger age was associated with better recovery as well. Factors that did not appear to affect recovery were the type of apheresis treatment, gender, disease duration, or the disease-modifying treatment the patient was on at the time of the relapse.

Study limitations included the retrospective nature of the analysis, the time of determination of the outcome measure (immediately at the cessation of apheresis treatment, which could have prevented assessment of delayed recovery), and the lower number of patients who received IA compared to PE. The disease-modifying treatments that the patients were on was not specified in the study. This is a potential factor that could influence recovery. However, the long-term disease-modifying treatments these patients were on did not seem to affect the recovery outcome measured.

COMMENTARY

Kleiter et al provided valuable information pertaining to the treatment of NMOSD. Based on this analysis, it appears that both types of apheresis treatments are equally effective for recovery from relapses in NMOSD. The study results demonstrated factors that influence recovery, and, most importantly, emphasized that early initiation of apheresis was the strongest predictor of response.

Given the often-severe nature of NMOSD relapses and the high incidence of refractoriness to conventional IV steroid treatment, it is imperative that more effective treatments like apheresis be initiated as soon as possible after symptom onset to prevent permanent residual disability from these relapses.