Treatment regimens for neuromyelitis optica spectrum disorder attacks: a retrospective cohort study

Abstract

Background: Neuromyelitis optica spectrum disorder (NMOSD) attacks require an urgent probabilistic anti-inflammatory therapeutic strategy. As inadequately treated attacks result in disability, there is a need to identify the optimal attack-treatment regimen. Our study aimed to identify predictors of outcome after a first attack in patients with an NMOSD presentation and propose the best treatment strategy.

Methods: We performed a retrospective cohort study on the French national NMOSD registry (NOMADMUS), a nested cohort of the French multiple sclerosis observatory (OFSEP) recruiting patients with NMOSD presentations in France. We studied the first attack for any independent locations of clinical core characteristic of NMOSD, in treatment-naïve patients. The primary outcome was the evolution of the Expanded Disability Status Scale (EDSS) score at 6 months, stratified in two ways to account for recovery (return to baseline EDSS score) and treatment response (classified as "good" if the EDSS score decreased by ≥ 1 point after a nadir EDSS score ≤ 3, or by ≥ 2 points after a nadir EDSS score > 3). We used ordinal logistic regression to infer statistical associations with the outcome.

Results: We included 211 attacks among 183 patients (104 with anti-AQP4 antibodies, 60 with anti-MOG antibodies, and 19 double seronegative). Attack treatment regimens comprised corticosteroids (n = 196), plasma exchanges (PE; n = 72) and intravenous immunoglobulins (n = 6). Complete recovery was reached in 40 attacks (19%) at 6 months. The treatment response was "good" in 134 attacks (63.5%). There was no improvement in EDSS score in 50 attacks (23.7%). MOG-antibody seropositivity and short delays to PE were significantly and independently associated with better recovery and treatment response.

Conclusions: We identified two prognostic factors: serostatus (with better outcomes among MOG-Ab-positive patients) and the delay to PE. We, therefore, argue for a more aggressive anti-inflammatory management of the first attacks suggesting an NMOSD presentation, with the early combination of PE with corticosteroids.

Keywords: Corticosteroids; MOGAD; Neuromyelitis optica; Plasma exchanges; Relapses; Therapeutics.

Fig. 1

We classified the recovery as “complete”, “partial”, or “absent” using a relative and an absolute definition. The relative definition was that proposed by Kleiter et al. [17], classifying the recovery. The absolute definition described the treatment response, based on the EDSS improvement at 6 months

Fig. 2

Treatment regimens structured as three therapeutic lines (A) and corticosteroids, PE, and IVIG usage at each line (B). The size of each circle is proportional to the number of attacks. The color corresponds to the mean delay. PE plasma exchange, IVIG intravenous immunoglobulins

Fig. 3

6-Month clinical outcome, presented as bar plots. We classified the recovery as “complete”, “partial”, or “absent” using a relative and an absolute definition. The relative definition was that proposed by Kleiter et al. [17], classifying the recovery as “complete” if the 6-month EDSS score reached the score before the attack, “partial” if recovery was incomplete, and “absent” if there was no improvement or a clinical deterioration. The absolute definition described the treatment response, based on the EDSS improvement at 6 months, classifying the response as “good” if the 6-month EDSS score showed a decrease of ≥ 1 point in the case of nadir EDSS score ≤ 3 or a reduction of ≥ 2 points in the case of a nadir EDSS score > 3. Treatment response was classified as “poor” if the EDSS score decrease was slighter and as “absent” if the EDSS score remained unchanged or if it worsened. Counts and percentages are shown for each bar. AQP4+: NMOSD–AQP4+; MOG+: NMOSD–MOG+; DN: NMOSD–DN (double seronegative)