Apheresis therapies for NMOSD attacks: A retrospective study of 207 therapeutic interventions

Abstract

Objective: To analyze whether 1 of the 2 apheresis techniques, therapeutic plasma exchange (PE) or immunoadsorption (IA), is superior in treating neuromyelitis optica spectrum disorder (NMOSD) attacks and to identify predictive factors for complete remission (CR).

Methods: This retrospective cohort study was based on the registry of the German Neuromyelitis Optica Study Group, a nationwide network established in 2008. It recruited patients with neuromyelitis optica diagnosed according to the 2006 Wingerchuk criteria or with aquaporin-4 (AQP4-ab)-antibody-seropositive NMOSD treated at 6 regional hospitals and 16 tertiary referral centers until March 2013. Besides descriptive data analysis of patient and attack characteristics, generalized estimation equation (GEE) analyses were applied to compare the effectiveness of the 2 apheresis techniques. A GEE model was generated to assess predictors of outcome.

Results: Two hundred and seven attacks in 105 patients (87% AQP4-ab-antibody seropositive) were treated with at least 1 apheresis therapy. Neither PE nor IA was proven superior in the therapy of NMOSD attacks. CR was only achieved with early apheresis therapy. Strong predictors for CR were the use of apheresis therapy as first-line therapy (OR 12.27, 95% CI: 1.04-144.91, p = 0.047), time from onset of attack to start of therapy in days (OR 0.94, 95% CI: 0.89-0.99, p = 0.014), the presence of AQP4-ab-antibodies (OR 33.34, 95% CI: 1.76-631.17, p = 0.019), and monofocal attack manifestation (OR 4.71, 95% CI: 1.03-21.62, p = 0.046).

Conclusions: Our findings suggest early use of an apheresis therapy in NMOSD attacks, particularly in AQP4-ab-seropositive patients. No superiority was shown for one of the 2 apheresis techniques.

Classification of evidence: This study provides Class IV evidence that for patients with NMOSD, neither PE nor IA is superior in the treatment of attacks.

Figure 1. Study flow chart

HD-S = high-dose IV steroids; IA = immunoadsorption; PE = plasma exchange.

Figure 2. Overview of apheresis therapies

Plasma exchange and immunoadsorption were applied at similar frequencies for escalation from first- to fifth-line treatment (A) and for various clinical manifestations (B) of NMOSD attacks. The chi-square test was used for statistical analysis. IA = immunoadsorption; MY = myelitis; ON = optic neuritis; PE = plasma exchange.

Figure 3. Clinical outcome of apheresis therapies for NMOSD attacks

Remission status of all attacks (total n = 207) treated with plasma exchange (A) or immunoadsorption (B). Missing data plasma exchange: 1st line, n = 1; 2nd line, n = 4; 3rd line, n = 6; and 4th line, n = 1. (C) Short-term remission status after first- or second-line therapy with plasma exchange or immunoadsorption. Treatment courses with PE/IA as first- and second-line therapy were excluded (n = 2). Missing data plasma exchange: 1st line, n = 1 and 2nd line, n = 4. Generalized estimation equations with complete remission as the dependent variable were used for statistical analysis. (D) Change in EDSS after first or second-line therapy with plasma exchange (gray triangles) or immunoadsorption (red triangles). Missing data plasma exchange: 1st line, n = 19; 2nd line, n = 30; missing data immunoadsorption: 1st line, n = 7 and 2nd line, n = 15. One out of range value (immunoadsorption, −6.0) is not shown. Generalized estimation equations were used for statistical analysis. The Median is highlighted as black line. (E) Short-term remission status after apheresis therapy according to time intervals of attack onset to start of therapy. CR = complete remission; IA = immunoadsorption; NR = no remission; PE = plasma exchange; PR = partial remission.