Attacks In Neuromyelitis Optica Spectrum Disorders Research Articles

Risk factors and prognosis of orotracheal intubation in aquaporin-4-IgG neuromyelitis optica spectrum disorder attacks

BackgroundAquaporin-4 immunoglobulin G Neuro Myelitis Optica spectrum disorders attacks (NMOSD-AQP4-IgG+ attacks) can cause respiratory failure requiring orotracheal intubation (OTI), but the risk factors and outcomes of OTI during attacks remain unclear. Our primary objective was to identify the clinical and radiological risk factors for OTI in NMOSD-AQP4-IgG+ attacks. As a secondary objective, we aimed to evaluate the prognosis of OTI-attacks.MethodsWe retrospectively analyzed NMOSD-AQP4-IgG+ attacks at the Pitié-Salpêtrière Hospital (Jan 2010–Jan 2021), excluding isolated optic neuritis. The primary outcome was the need for OTI due to neurological dysfunction an attack (OTI-attack). The secondary outcome was attack’s poor recovery after 12 months, defined as a modified Rankin score (mRS) > 2 in patients with an initial mRS ≤ 2, or an increase ≥ 1 point in mRS in other patients. Analyses were performed using a binomial generalized linear mixed model, with a random intercept for the patient ID to account for within-patient correlations.ResultsSeventy-three attacks in 44 patients NMOSD-AQP4-IgG+ were analyzed. Of 73 attacks, 8 (11%) required OTI during the attack, related to acute restrictive respiratory failure (n = 7) and/or severe swallowing disorder (n = 2). None of the OTI-attacks occurred in patients previously treated with active disease-modifying treatment (DMT), while 36 (55.4%) of the non-OTI-attacks occurred in patients who were already on active DMT. On admission, OTI-attacks were more likely to have upper limbs motor paresis of (75.0% versus 29.2%, p = 0.366) and dyspnea (3 [50.0%] versus 4 [6.6%], p = 0.002) compared to non-OTI-attacks. MRI analysis showed that OTI-attacks had edematous lesions in the cervical spinal cord, mainly at levels C1 (75% versus 0% in non-OTI-attacks), C2 (75% versus 1.9%), C3 (62.5% versus 1.9%), and C4 and C5 levels (50% versus to 3.9%). One OTI-attack resulted in the death of one patient. Five patients with OTI-attack had mRS ≤ 2 one year after OTI-attack. Two (25%) OTI-attacks had poor recovery compared to 15 (24.2%) non-OTI-attacks (p = 0.468).ConclusionOTI-attacks occurred in untreated NMOSD-AQP4-IgG+ patients and were associated with edematous upper cervical lesions. The prognosis of these attacks may be favorable, and warrant maximal medical and supportive treatment.Trial registration This was a retrospective observational monocentric cohort study nested in the NOMADMUS cohort (ClinicalTrials.gov Identifier: NCT02850705)Graphical

Patterns of neuromyelitis optica spectrum disorder attacks in different age groups and sexes depending on the status of immunosuppressive therapy: A retrospective cohort study.

The association between onset age and sex with relapse risk in neuromyelitis optica spectrum disorder (NMOSD) remains inconclusive. We aimed to describe the clinical features of patients with NMOSD in different age groups and sexes and to analyse relapse characteristics pre- and post-immunosuppressive therapy (IST). Patients with NMOSD were retrospectively reviewed from our clinical centre's database. Demographic and clinical data, attack presentation, and disease course pre- and post-IST were investigated. We also analysed the effect of onset age on the annualized relapse rate and relapse risk according to sex and IST status. Interactions on the additive scale between onset age and sex were analysed. A restricted cubic spline was used to analyse potential nonlinear correlations. Longitudinal changes in the Expanded Disability Status Scale score across NMOSD attacks were analysed using linear mixed-effect models. In total, 533 patients experienced 1394 attacks pre-IST and 753 relapses post-IST. Older age at onset was correlated with more myelitis attacks but fewer optic neuritis attacks, with no sex-related differences in attack presentation. Pre-IST, relapse risk increased with age at onset in women, while a U-shaped correlation between onset age and relapse risk was found in men. Post-IST, an inverted U-shaped association between the predicted relapse risk and onset age was observed in women. Conversely, a negative correlation between the predicted relapse risk and onset age was found in men. Overall, a higher ratio of myelitis attacks was found post-IST. Patients of different onset ages and sexes had different relapse patterns before and after IST.

Efficacy and safety of inebilizumab in Asian participants with neuromyelitis optica spectrum disorder: Subgroup analyses of the N-MOmentum study.

Inebilizumab, an anti-CD19 B cell-depleting antibody, reduced the risk of a neuromyelitis optica spectrum disorder (NMOSD) attack, disability worsening, magnetic resonance imaging (MRI) lesion activity, and disease-related hospitalizations in participants with NMOSD in the N-MOmentum study (NCT02200770). However, the efficacy and safety outcomes of inebilizumab specific to an Asian population were not fully reported. Therefore, subgroup analyses of the N-MOmentum study were conducted post hoc to evaluate the efficacy and safety of inebilizumab in Asian participants with NMOSD. The N-MOmentum study was a multicenter, double-blind, randomized, placebo-controlled phase 2/3 trial with an open-label extension period (OLP). In the subgroup analyses, data from Asian participants from the N-MOmentum study were compared with those of non-Asian participants. Eligible participants were randomly allocated (3:1) to receive 300mg intravenous (IV) inebilizumab or placebo on Days 1 and 15. Participants who had an NMOSD attack or completed the randomized controlled period (RCP) could enter the OLP, where they received inebilizumab for ≥2 years. All participants who entered the OLP received inebilizumab 300mg IV every 6 months. Overall, 230 participants received treatment (174 received inebilizumab and 56 received placebo), of whom 47 were Asian (39 received inebilizumab and 8 received placebo). Baseline characteristics were similar between the Asian and non-Asian subgroups, except for disease duration, annualized relapse rate prior to randomization in this study, and previous maintenance therapy. In the Asian subgroup, the risk of NMOSD attacks was reduced with inebilizumab versus placebo (hazard ratio, 0.202) and the attack-free rate at 28 weeks was 82.1% with inebilizumab versus 37.5% with placebo, in the 6-month RCP. NMOSD attack rates were comparable between the Asian and non-Asian subgroups. In the Asian subgroup, the rates of Expanded Disability Status Scale worsening from baseline, active MRI lesions, and disease-related hospitalizations tended to be lower in the inebilizumab group than in the placebo group; similar results were shown in the non-Asian subgroup. For long-term efficacy and safety (RCP and OLP), the annualized adjudicated NMOSD attack rate in Asian participants treated with inebilizumab was reduced (0.096) compared with that at baseline (1.04), with a mean follow-up period of inebilizumab treatment of 3.38 years, which was consistent with the results in the non-Asian subgroup. The risk of NMOSD attack decreased with prolonged duration of treatment in both the inebilizumab/inebilizumab and placebo/inebilizumab groups in the Asian and non-Asian subgroups. The incidence of treatment-emergent adverse events (TEAEs) was similar between the Asian and non-Asian subgroups. In the Asian and non-Asian subgroups, 15.2% and 35.2% of participants, respectively, had at least one serious TEAE and/or Grade ≥3 TEAE during long-term therapy. No deaths occurred in the Asian subgroup whereas three deaths occurred in the non-Asian subgroup. Inebilizumab reduced the risk of an NMOSD attack, progression of disability, MRI lesion activity, and disease-related hospitalizations in Asian participants with NMOSD. The efficacy of inebilizumab in reducing NMOSD attacks continued without any unexpected safety signals or concerns during long-term use in Asian participants.

Inebilizumab for neuromyelitis optica spectrum disorders in Italy: a budget impact model

ABSTRACT Background The Italian National Health Service (INHS) has recently reimbursed the monoclonal antibody inebilizumab as a second line monotherapy after rituximab (RTX) use for neuromyelitis optica spectrum disorders (NMOSD) patients ≥ 18 years anti-aquaporin 4 antibody-immunoglobulin G positive, who experienced a relapse in the last year or cannot receive RTX, if incident patients. Other INHS-reimbursed drugs for NMOSD treatment are satralizumab, eculizumab and, off-label, besides RTX, ocrelizumab, tocilizumab, and immunosuppressants. Research design and methods A 3-year (2023–2025) prevalence-based budget impact model following the INHS viewpoint compared the costs and the NMOSD attacks without (1st scenario) and with inebilizumab (2nd scenario). The epidemiology of NMOSD, and the INHS-funded healthcare resources (drugs and their administration; specialist visits; hospitalizations due to drug-related adverse events and NMOSD attacks) were obtained from the literature. One-way, threshold value and scenario sensitivity analyses investigated the robustness of the baseline findings. Results During 2023–2025 inebilizumab saves the INHS €8,373,125.13 (1st scenario: €176,770,028.63; 2nd scenario: €168,396,903.50) and 12.74 NMOSD attacks (1st scenario: 213.94; 2nd scenario: 201.19). Sensitivity analyses confirmed the robustness of the baseline results. Conclusion Inebilizumab reduces the INHS expenditure for NMOSD drugs. Future research should explore the cost-effectiveness of inebilizumab vs other NMOSD-targeting drugs in Italy.

Inebilizumab reduces neuromyelitis optica spectrum disorder risk independent of FCGR3A polymorphism.

Inebilizumab, a humanized, glycoengineered, IgG1 monoclonal antibody that depletes CD19+ B-cells, is approved to treat aquaporin 4 (AQP4) IgG-seropositive neuromyelitis optica spectrum disorder (NMOSD). Inebilizumab is afucosylated and engineered for enhanced affinity to Fc receptor III-A (FCGR3A) receptors on natural killer cells to maximize antibody-dependent cellular cytotoxicity. Previously, the F allele polymorphism at amino acid 158 of the FCGR3A gene (F158) was shown to decrease IgG-binding affinity and reduce rituximab (anti-CD20) efficacy for NMOSD attack prevention. In contrast, our current findings from inebilizumab-treated NMOSD patients indicate similar clinical outcomes between those with F158 and V158 allele genotypes.

Initial BMI effects on clinical presentation and prognosis in neuromyelitis optica spectrum disorder.

To investigate the correlation among body mass index at onset, clinical features, and prognosis in patients with neuromyelitis optica spectrum disorder. This retrospective cohort studied patients with neuromyelitis optica spectrum disorder from January 2015 to January 2022, grouping them by body mass index at onset. Demographics and clinical records were reviewed. Anderson-Gill, Kaplan-Meier, and Cox models evaluated the body mass index's effect on relapse risk and long-term outcomes. Of 246 patients with 799 neuromyelitis optica spectrum disorder attacks study, 36 patients had low, 133 had normal, 77 had high body mass index, with a mean onset age of 40 ± 13 years, and the population was 88% female. The medium follow-up time was 49 months; AQP4-IgG was found in 193 (78%) patients. Onset and relapse of area postrema syndrome were less frequent in patients with a normal body mass index. The annual relapse rate after immunosuppressive therapy was significantly lower in patients with a low body mass index. In the multivariable analysis, statistical correlation still existed between body mass index at onset and risk of relapse (HR = 1.03, 95% CI: 1.03-1.03, P < 0.001), risk of severe attack (HR = 0.92, 95% CI: 0.86-0.98, P = 0.013), risk of visual disability (HR = 0.9, 95% CI: 0.81-1, P = 0.047), and overall risk of disability (HR = 0.89, 95% CI: 0.82-0.98, P = 0.015) after adjusting various variables. Lower body mass index at onset was associated with less frequent relapse but poor prognosis.

Risk and characteristics of attacks occurring after vaccination in patients with neuromyelitis optica spectrum disorders: A systematic review and meta-analysis.

Vaccination in patients with neuromyelitis optica spectrum disorders (NMOSD) is challenging because there is a concern that vaccines can lead to clinical attacks. However, little is known about the risk and the characteristics of attacks occurring after vaccination. We performed a systematic review and meta-analysis using PubMed and Embase databases to estimate a summary frequency of attacks occurring after vaccination and describe the clinical features of theses attacks. We defined attacks occurring after vaccination as typical NMOSD attacks that occurred up to 30 days after vaccine administration. For the frequency of attacks occurring after vaccination, we selected observational studies that reported the number of attacks and total number of patients that received vaccines; for the clinical description of the attacks, case reports and case series were also included. We included 377 participants from 5 studies to estimate the frequency of NMOSD attacks occurring after vaccination. We found a summary frequency of of 2% (95% CI 1-4%, I2=0%). We evaluated 17 studies to identify that 13 different vaccines were associated with NMOSD attacks. A higher-than-expected proportion of males, simultaneous optic neuritis and transverse myelitis attacks, and anti-aquaporin 4 antibody negative cases were identified in vaccine-associated attacks from 24 participants from 17 studies. Nearly two-thirds of attacks occurring after vaccination were an initial event of NMOSD. The frequency of NMOSD attacks occurring after vaccination is low and non-specific to different vaccine technologies. Our work reinforces the safety of vaccine recommendations in patients with NMOSD.

Visual disability in neuromyelitis optica spectrum disorders: prognostic prediction models.

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory disease of the central nervous system characterized by simultaneous or consecutive episodes of acute optic neuritis and transverse myelitis. Attacks of NMOSD can result in the accrual of severe visual disability over time. This study aimed to develop and validate prognostic models for visual disability risk within 1, 3, and 5 years. Medical records of NMOSD patients were retrospectively analyzed. The least absolute shrinkage and selection operator (LASSO) regression algorithm and univariate and multivariate Cox regression analyses were performed to select predictors of visual disability. Two models predicting the probability of visual disability in 1, 3, and 5 years were developed based on different selections and displayed as nomograms. Risk scores were calculated for every patient, and a cut-off point was obtained to recognize patients at high risk. In total, 161 (25.2%) patients developed visual disabilities during the follow-up period. Four visual disability-related factors were selected using LASSO regression: optic neuritis (ON) onset, higher annual relapse rate (ARR) before maintenance therapy, no maintenance immune suppression therapy (IST), and initial severe attack. Three additional predictors were determined using multivariate Cox regression: male sex, age at first onset, and positive AQP4-IgG serology. Discrimination and calibration were satisfied, with concordance indexes (C-index) close to 0.9 in both models. Decision curve analysis showed good clinical usefulness in both models, and Kaplan-Meier curves showed satisfactory discrimination between patients with high risk and low risk by the cut-off points. This study reported predictors of visual disability and generated nomograms. High-risk patients need more active treatment and management to avoid unfavorable outcomes.

Attack adjudication in neuromyelitis optica spectrum disorder: Substantiation of criteria by magnetic resonance imaging and biomarkers in N-MOmentum

Background: The N-MOmentum trial investigated safety and efficacy of inebilizumab in participants with neuromyelitis optica spectrum disorder (NMOSD). Objective: Evaluate the attack identification process and adjudication committee (AC) performance in N-MOmentum. Methods: Adults (n = 230) with NMOSD and Expanded Disability Status Scale score ⩽8 were randomized (3:1) to inebilizumab 300 mg or placebo. The randomized controlled period was 28 weeks or until adjudicated attack. Attacks were adjudicated according to 18 predefined criteria. Magnetic resonance imaging (MRI) and biomarker (serum glial fibrillary acidic protein [sGFAP]) analyses were performed. Results: A total of 64 participant-reported neurological events occurred; 51 (80%) were investigator-determined to be attacks. The AC confirmed 43 of the investigator-determined attacks (84%). There was high inter- and intra-AC-member agreement. In 25/64 events (39%) and 14/43 AC-adjudicated attacks (33%), MRI was reviewed during adjudication. Retrospective analysis revealed new domain-specific T1 and T2 MRI lesions in 90% of adjudicated attacks. Increased mean sGFAP concentrations (>2-fold change) from baseline were observed in 56% of adjudicated attacks versus 14% of investigator-determined attacks rejected by the AC and 31% of participant-reported events determined not to be attacks. Conclusion: AC adjudication of NMOSD attacks according to predefined criteria appears robust. MRI lesion correlates and sGFAP elevations were found in most adjudicated attacks.

Neuromyelitis Optica Spectrum Disorder: An Early Diagnosis to Prevent Blindness and Paraplegia

Neuromyelitis optica spectrum disorder (NMOSD), also referred to as Devic’s disease, is a rare autoimmune disease of the central nervous system that primarily affects both the optic nerve (optic neuritis) and the spinal cord (myelitis). Patients presenting solely with optic neuritis or transverse myelitis can make diagnosis difficult. If left untreated, it may result in blindness and paralysis. Early and accurate diagnosis is crucial for treating and preventing further NMOSD attacks. This article describes the case of a previously healthy patient who presented with NMOSD. In addition, the clinical presentation, diagnostics, and treatment methods are discussed.

Serum neurofilament light chain levels at attack predict post-attack disability worsening and are mitigated by inebilizumab: analysis of four potential biomarkers in neuromyelitis optica spectrum disorder

ObjectiveTo investigate relationships between serum neurofilament light chain (sNfL), ubiquitin C-terminal hydrolase L1 (sUCHL1), tau (sTau) and glial fibrillary acidic protein (sGFAP) levels and disease activity/disability in neuromyelitis optica spectrum...

Acute NMOSD Attack in the Setting of Pembrolizumab Therapy: A Case Report (P13-5.009)

Acute NMOSD Attack in the Setting of Pembrolizumab Therapy: A Case Report (P13-5.009)

Association of B cell Subsets and Aquaporin-4 antibody titers with Disease Activity in Participants in the N-MOmentum trial Receiving Inebilizumab Treatment (S5.005)

Association of B cell Subsets and Aquaporin-4 antibody titers with Disease Activity in Participants in the N-MOmentum trial Receiving Inebilizumab Treatment (S5.005)

Safety and Efficacy of Inebilizumab in AQP4+ NMOSD Participants with History of Immunosuppression Treatment Prior to N-MOmentum Study (P13-5.003)

Safety and Efficacy of Inebilizumab in AQP4+ NMOSD Participants with History of Immunosuppression Treatment Prior to N-MOmentum Study (P13-5.003)

Granulocyte activation markers in cerebrospinal fluid differentiate acute neuromyelitis spectrum disorder from multiple sclerosis

BackgroundGranulocyte invasion into the brain is a pathoanatomical feature differentiating neuromyelitis optica spectrum disorder (NMOSD) from multiple sclerosis (MS). We aimed to determine whether granulocyte activation markers (GAM) in cerebrospinal...

Adding erythropoietin to intravenous methylprednisolone in acute treatment of attacks of neuromyelitis optica spectrum disorders: A randomized controlled trial.

Background: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease of the central nervous system (CNS) that prompts immediate potent treatment. Delaying treatment could leave debilitating sequelae. As erythropoietin (EPO) has shown neuroprotective effects, we studied the effects of adding EPO to intravenous methylprednisolone (IVMP) in patients with acute attacks of NMOSD. Methods: NMOSD cases with acute attacks were included. Cases of optic neuritis (ON) and those with myelitis were separated. After randomization [with block sizes of 2 (1:1 ratio)], the patients in the intervention group received IVMP 1000 mg/day and intravenous (IV) EPO 20000 U/day for five days. IVMP 1000 mg/day and normal saline (NS) were administered in the control group. Staged eye score and motor forces were evaluated in the patients with ON and myelitis, respectively, at the time of the attack and three months later. Primary patient allocation and clinical assessments were blinded to the physicians. Results: Mean age of participants was 53.87 ± 11.53 years. At follow-up, in the ON arm, the median improvement in staged eye score was 2 in the control and 5 in the intervention group. The difference was significant (P < 0.001). In the myelitis group, none of the patients in the control group had improvement in motor forces. All the patients in the intervention group showed substantial improvement with minimal or no remaining weakness. The difference was statistically significant (P = 0.029). Conclusion: The results show the possible benefit of adding EPO to the classic IVMP in attacks of NMOSD in both visual and motor aspects.

Therapeutic efficacy and safety of plasmapheresis in elderly patients with neuromyelitis optica spectrum disorder: a single-center observational study

Neuromyelitis optica spectrum disorder (NMOSD) is a devastating autoimmune disorder with cycles of escalating relapse. Rates of diagnosis in the elderly are increasing. Therapeutic decision-making is more challenging in elderly patients due to multiple comorbidities and high risk of drug-induced side effects. This retrospective study assessed the efficacy and safety of standard plasma exchange (PLEX) treatment in an elderly population with NMOSD. Seventy-six patients with NMOSD who received PLEX were apportioned to two groups as either elderly (⩾60 years, n = 26) or young (<60 years) at the time of the first procedure. Therapeutic response was judged according to functional recovery at 6 months, as reflected by Expanded Disability Status Scale (EDSS) and visual outcome scale (VOS) scores. The mean age of the 26 elderly patients was 67.7 ± 7.9 years (range 60-87 years); the population was predominantly female (88.5%). PLEX sessions were generally well tolerated among the elderly. Compared with the young patients, the elderly had significantly more comorbidities and concomitant medications. Twenty-four (96.0%) elderly patients showed functional improvement at 6 months after PLEX, of which 15 (60.0%) experienced moderate-to-marked improvement. Six months after the initial PLEX treatment, the patients overall experienced a significant improvement in EDSS and VOS scores. Logistic regression showed that severe optic neuritis attack was a significant independent prognostic factor associated with poor PLEX response. The groups were comparable regarding overall or serious adverse events. The rate of transient hypotension was significantly higher in the elderly compared with the young. PLEX is an effective and safe therapy for elderly patients with NMOSD and should be considered a treatment option during NMOSD attacks. In the elderly, preventive measures against hypotension are recommended before PLEX.

A Phase 3 Efficacy and Safety Study of Ravulizumab in Adult Patients With Neuromyelitis Optica Spectrum Disorder: Study Design and Methodology

Objective To present the design and rationale for the phase 3 trial ALXN-1210-NMO-307 (NCT04201262). Background Eculizumab is a complement component 5 (C5) inhibitor approved for adults with anti-aquaporin-4 antibody-positive (AQP4+) neuromyelitis optica spectrum disorder (NMOSD). Ravulizumab, which binds the same C5 epitope, has a longer half-life with an extended dosing interval (every 8 vs every 2 weeks). We designed an innovative trial without concurrent placebo exposure to assess the efficacy and safety of ravulizumab in adults with AQP4+ NMOSD. Design/Methods NA. Results ALXN1210-NMO-307 is an open-label, multicenter, single-arm study using the placebo group from the PREVENT trial as a comparator. Constancy with PREVENT is maintained, including similar patient populations, adjudication procedures, and endpoints. Sensitivity analyses are prespecified to account for differences in patient characteristics. To measure confounding, an E-value is calculated for the primary endpoint (time-to-first adjudicated on-trial relapse). Given the serious impact of NMOSD attacks, eculizumab approval precluded the use of a concurrent comparator for ethical reasons, as it would require assigning patients to placebo when effective treatments exist. A non-inferiority efficacy trial was also considered but recruiting the very large sample size to adequately power the study was not feasible for this ultra-rare disease. Thus, a standard randomized clinical trial design was used. The trial enrolled 58 adults with EDSS score = 7 to receive an infusion of ravulizumab every 8 weeks after the loading dose. The primary treatment period will end when the last enrolled patient reaches week 50 unless a predefined number of patients have an adjudicated on-trial relapse by that time. The entire treatment period will last up to ∼4.5 years. Conclusions ALXN1210-NMO-307 is an ongoing study evaluating the efficacy and safety of ravulizumab in patients with AQP4+ NMOSD. It is designed to be consistent with PREVENT, and robust statistical methods will address the potential impact of an external comparator.

Inebilizumab: A Review in Neuromyelitis Optica Spectrum Disorder.

Inebilizumab (Uplizna®) is a recently approved monoclonal antibody for use in adults with neuromyelitis optica spectrum disorder (NMOSD) who are anti-aquaporin-4 (AQP4) antibody seropositive. Inebilizumab targets the B cell antigen CD19 and effectively depletes circulating B cells, thus suppressing inflammatory NMOSD attacks that are potentially disabling or life-threatening. It is approved as an intravenous infusion in several countries. In the pivotal phase 2/3 N-MOmentum trial, inebilizumab reduced the risk of NMOSD attacks compared with placebo, including in AQP4-antibody seropositive patients. Inebilizumab also significantly reduced the risk of disability score worsening, the number of NMOSD-related hospitalisations and MRI lesion count, but had no significant effect on low-contrast binocular vision. The treatment effect on relapse risk and disability scores was sustained in inebilizumab-treated patients for ≥ 4 years during the open-label extension. Inebilizumab was generally well tolerated, with the most common adverse events being urinary tract infection and arthralgia. Thus, inebilizumab is an effective treatment option for adults with AQP4-antibody seropositive NMOSD.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40263-022-00949-7.

Analysis of Pregnancy-Related Attacks in Neuromyelitis Optica Spectrum Disorder

Risk of relapse may be increased in the postpartum period of neuromyelitis optica spectrum disorder (NMOSD). Information regarding factors associated with pregnancy-related attacks is still lacking. To identify factors associated with pregnancy-related NMOSD attacks, investigate the integrated annualized relapse rate (ARR) and Expanded Disability Status Scale (EDSS) score in each phase of pregnancy, and summarize pregnancy outcomes and complications in patients with NMOSD. An electronic search was performed in the MEDLINE, PubMed in-process and non-MEDLINE, EMBASE, Web of Science, and Cochrane databases using the OvidSP search platform, updated through December 30, 2021. All published and unpublished studies in English were considered, covering all patients with NMOSD with an informative pregnancy. Two independent reviewers extracted the published data with a standardized procedure following MOOSE and PRISMA guidelines. The end points were calculated with the DerSimonian and Laird inverse variance (for random effects) method. The primary outcome was the rate of pregnancies with pregnancy-related NMOSD attacks, measured by risk ratios (RRs). The mean differences (MDs) in ARR and EDSS scores between each phase of pregnancy, pregnancy outcomes, and complications were defined as the secondary outcomes. A total of 15 studies were analyzed, including 443 patients with NMOSD with 639 informative pregnancies. Patients receiving immunosuppressive treatment during pregnancy (RR, 0.43; 95% CI, 0.32-0.57; P < .001) and with older age at conception (RR, 0.67; 95% CI, 0.47-0.95; P = .02) had lower rates of pregnancy with pregnancy-related attacks. The increase in the ARR was highest in the first trimester after delivery compared with before pregnancy (MD, 1.28; 95% CI, 0.94-1.62; P < .001). The EDSS scores increased significantly both during pregnancy (MD, 0.44; 95% CI, 0.20-0.69; P < .001) and in the postpartum period (MD, 0.88; 95% CI, 0.51-1.26; P < .001) compared with before pregnancy. This systematic review and meta-analysis found that receiving immunosuppressive treatment during pregnancy and older age at conception were associated with reduced risk of pregnancy-related NMOSD attacks, which mostly occurred in the first trimester of the postpartum period, although more high-quality prospective studies are needed.