Oxford University Hospitals

Author Of 5 Presentations

Neuromyelitis Optica and Anti-MOG Disease Oral Presentation

FC01.01 - Long-term efficacy and safety of eculizumab monotherapy in AQP4+ neuromyelitis optica spectrum disorder

Speakers
Presentation Number
FC01.01
Presentation Topic
Neuromyelitis Optica and Anti-MOG Disease
Lecture Time
13:00 - 13:12

Abstract

Background

In the randomized, double-blind, placebo-controlled, phase 3 PREVENT trial (NCT01892345), eculizumab was well tolerated and significantly reduced relapse risk vs placebo in patients with aquaporin-4 immunoglobulin G-positive (AQP4+) neuromyelitis optica spectrum disorder (NMOSD). The treatment effect observed in a prespecified subgroup of patients who received eculizumab monotherapy vs placebo alone (i.e. without concomitant immunosuppressive therapy [IST]) was consistent with the overall population.

Objectives

To examine the long-term efficacy and safety of eculizumab monotherapy in patients with AQP4+ NMOSD during PREVENT and/or its ongoing open-label extension (OLE; NCT02003144).

Methods

During PREVENT and its OLE, adults with AQP4+ NMOSD received eculizumab (maintenance dose, 1200 mg/2 weeks) or placebo (PREVENT only) with/without concomitant IST. Relapses, hospitalizations, IST changes and adverse events (AEs) with eculizumab monotherapy (PREVENT and its OLE; interim data cut-off, July 31, 2019) or with placebo alone (PREVENT) were descriptively analyzed post hoc.

Results

During PREVENT and/or its OLE, 33 patients received eculizumab monotherapy for a total of 85.3 patient-years (PY). Adjudicated relapses occurred in 1/33 patients (annualized relapse rate [ARR], 0.012; 95% confidence interval [CI]: 0.002–0.082), vs 7/13 with placebo alone in PREVENT. At 192 weeks, 96.2% of patients who received eculizumab monotherapy were relapse-free (95% CI: 0.757–0.994) vs 93.8% of patients who received eculizumab with concomitant IST (95% CI: 0.867–0.972). No patients receiving eculizumab monotherapy required hospitalization for a relapse and none started an IST. The treatment-related AE rate with eculizumab monotherapy in PREVENT and its OLE was similar to that with placebo alone in PREVENT (181.0 and 186.0 events/100 PY, respectively), the infection rate was similar between these groups (174.1 vs 186.0 events/100 PY), and the treatment-related serious AE rate was lower with eculizumab monotherapy than with placebo alone (5.7 vs 23.3 events/100 PY). No meningococcal infections or deaths occurred among these patients.

Conclusions

A very high proportion of patients who had experienced 1–2 relapses in the pre-study year remained relapse-free through 192 weeks of eculizumab monotherapy. Long-term eculizumab monotherapy was well tolerated. These data support the long-term effectiveness of eculizumab monotherapy in reducing relapse risk in AQP4+ NMOSD.

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Neuromyelitis Optica and Anti-MOG Disease Oral Presentation

FC01.02 - Efficacy and safety of eculizumab in patients with neuromyelitis optica spectrum disorder previously treated with rituximab: findings from PREVENT

Speakers
Presentation Number
FC01.02
Presentation Topic
Neuromyelitis Optica and Anti-MOG Disease
Lecture Time
13:12 - 13:24

Abstract

Background

In PREVENT, eculizumab was associated with a significant reduction in relapse risk versus placebo and was well tolerated. In total, 46 patients (26/96 in the eculizumab arm, 20/47 in the placebo arm) were previously treated with the monoclonal antibody rituximab.

Objectives

To describe the efficacy and safety of eculizumab in patients in the PREVENT trial (NCT01892345) who had previously received rituximab.

Methods

Adults with aquaporin-4 immunoglobulin G-positive neuromyelitis optica spectrum disorder received eculizumab (maintenance dose, 1200 mg/2 weeks) or placebo with/without concomitant immunosuppressive treatment (except rituximab/mitoxantrone). A post hoc descriptive analysis was performed using data from patients with any prior rituximab treatment (within the previous year only for review of adverse events [AEs]) recorded more than 3 months before randomization.

Results

Baseline characteristics of the prior-rituximab subgroup were similar to those of the total PREVENT population; however, the subgroup included a lower proportion of Asian patients (10.9% vs 36.4% in total PREVENT) and greater representation from the Americas (58.7% vs 30.8%). In the subgroup, median times from last dose of rituximab to meningococcal vaccination and to first dose of study treatment were 31.7 and 38.7 weeks, respectively. Adjudicated relapses occurred in 1/26 patients (3.8%) and 7/20 patients (35.0%) in the eculizumab and placebo arms (hazard ratio: 0.093; 95% confidence interval: 0.011–0.755; p = 0.0055), respectively. Rates of AEs for eculizumab and placebo were 1025.8 and 1029.1 events/100 patient-years (100% of patients), respectively, and rates of serious AEs were 46.9 and 66.0 events/100 patient-years (38.9% and 47.1% of patients), respectively. Serious infections/infestations were recorded in 2/18 patients (11.1%) and 2/17 patients (11.8%) in the eculizumab and placebo arms, respectively.

Conclusions

In patients in PREVENT who had previously received rituximab, the risk of adjudicated relapse was significantly lower with eculizumab than with placebo. Rates of serious infections were similarly low with eculizumab and placebo.

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Neuromyelitis Optica and Anti-MOG Disease Oral Presentation

FC01.03 - Effect of satralizumab on relapse severity in neuromyelitis optica spectrum disorder (NMOSD): results from the Phase III SAkura studies

Speakers
Presentation Number
FC01.03
Presentation Topic
Neuromyelitis Optica and Anti-MOG Disease
Lecture Time
13:24 - 13:36

Abstract

Background

NMOSD is an autoimmune disorder characterized by acute, unpredictable relapses that result in accumulating disability. Satralizumab, a humanized, monoclonal recycling antibody that targets the interleukin-6 receptor, reduced relapse frequency and had a favourable safety profile vs placebo in two randomized, phase 3 clinical trials: SAkuraSky (satralizumab in combination with baseline immunosuppressants; NCT02028884), and SAkuraStar (satralizumab monotherapy; NCT02073279).

Objectives

To assess the impact of satralizumab on relapse severity in patients with NMOSD.

Methods

Patients in the SAkura studies received satralizumab 120mg or placebo at Weeks 0, 2, 4, and Q4W thereafter. This analysis was performed using data from the pooled intention-to-treat population across the double-blind periods of both studies. We assessed the severity of protocol-defined relapses (PDRs) by comparing patients’ Expanded Disability Status Scale (EDSS) score at PDR vs their score prior to relapse (last scheduled study visit). A similar analysis on optic neuritis PDRs was performed using visual Functional Systems Score (FSS). A PDR was categorised as severe if it resulted in a change of ≥2 points on the EDSS or visual FSS (optic neuritis analysis). Kaplan-Meier analyses were performed to assess time to first severe PDR. Additionally, the number of patients receiving acute therapy for any relapse was compared between treatment groups.

Results

Overall, 178 patients were included in the analyses. In the satralizumab group, 27 of 104 patients (26%) experienced a PDR vs 34 of 74 patients (46%) in the placebo group. The proportion of PDRs that were severe was lower in patients receiving satralizumab vs placebo (5 of 27 events [19%] vs 12 of 34 events [35%]). Similarly, the proportion of optic neuritis PDRs that were severe was lower in patients receiving satralizumab vs placebo (2 of 8 events [25%] vs 5 of 13 events [39%]). Across all patients, there was a 79% reduction in severe PDR risk with satralizumab vs placebo (hazard ratio [95% CI]; 0.21 [0.07–0.61]; p=0.002). A lower proportion of patients receiving satralizumab were prescribed acute relapse therapy vs placebo (38% vs 58%; odds ratio [95% CI] 0.46 [0.25–0.86], p=0.015).

Conclusions

Patients treated with satralizumab had a lower risk of severe relapse, and were less likely to receive acute relapse therapy compared with placebo. The number of patients with severe PDRs was low, so results should be interpreted with caution.

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Invited Presentations Invited Abstracts

HT07.02 - Presentation 02

Speakers
Authors
Presentation Number
HT07.02
Presentation Topic
Invited Presentations
Lecture Time
10:27 - 10:39
Neuromyelitis Optica and Anti-MOG Disease Oral Presentation

PS15.03 - Optical coherence tomography in aquaporin-4-IgG positive neuromyelitis optica spectrum disorders: a collaborative multi-center study

Abstract

Background

Optic neuritis (ON) is a frequent manifestation in aquaporin-4 antibody (AQP4-IgG) seropositive neuromyelitis optica spectrum disorders (NMOSD). Due to limited samples, existing optical coherence tomography (OCT) studies are inconsistent regarding retinal changes in eyes with a history of ON (NMO-ON) and without a history of ON (NMO-NON), and their functional relevance.

Objectives

The CROCTINO (Collaborative Retrospective Study on retinal OCT in Neuromyelitis Optica) project aims to reveal correlates of retinal pathology and to generate hypotheses for prospective OCT studies in NMOSD. The objective of this study was to analyze retinal changes of AQP4-IgG seropositive NMO-ON and NMO-NON eyes in an international cross-sectional OCT dataset.

Methods

Of 656 subjects, we enrolled 283 AQP4-IgG seropositive NMOSD patients and 72 healthy controls (HC) from 22 international expert centers. OCT data was acquired with Spectralis SD-OCT, Cirrus HD-OCT and Topcon 3D OCT-1. Mean thickness for the combined ganglion cell and inner plexiform layer (GCIP) and inner nuclear layer (INL) were calculated from macular volume scans. Clinical, functional and laboratory testing were performed at discretion of each center.

Results

We compared NMO-ON eyes (N = 260), NMO-NON eyes (N = 241) and HC eyes (N = 136). GCIP was reduced in NMO-ON (57.4 ± 12.2 µm) compared with NMO-NON (75.9 ± 7.7 µm; p < 0.001) and HC (81.4 ± 5.7 µm; p < 0.001). NMO-NON had thinner GCIP (p < 0.001) compared with HC. INL was thicker in NMO-ON (40.3 ± 3.9 µm) compared with NMO-NON (38.6 ± 3.9µm; p < 0.001), but not HC (39.4 ± 2.6 µm). Microcystic macular edema were visible in 6.6 % of NMOSD eyes.

Conclusions

AQP4-IgG seropositive NMOSD is characterized by a functionally relevant loss of retinal neuroaxonal content and a - probably inflammatory - increase of INL after ON. Our study further supports the existence of attack-independent damage in the visual system of patients with AQP4-IgG seropositive NMOSD.

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Presenter Of 1 Presentation

Invited Presentations Invited Abstracts

HT07.02 - Presentation 02

Speakers
Authors
Presentation Number
HT07.02
Presentation Topic
Invited Presentations
Lecture Time
10:27 - 10:39

Invited Speaker Of 1 Presentation

Invited Presentations Invited Abstracts

HT07.02 - Presentation 02

Speakers
Authors
Presentation Number
HT07.02
Presentation Topic
Invited Presentations
Lecture Time
10:27 - 10:39

Author Of 9 Presentations

Epidemiology Poster Presentation

P0457 - Evidence of Clostridium perfringens epsilon toxin involvement in neuromyelitis optica (ID 896)

Speakers
Presentation Number
P0457
Presentation Topic
Epidemiology

Abstract

Background

Two separate studies have reported that up to 23% of multiple sclerosis patients have antibodies against epsilon toxin from Clostridium perfringens, suggesting that the toxin may play a role in the disease.

Objectives

We investigated whether we could detect antibodies to epsilon toxin in the sera of UK patients with clinically definite neuromyelitis optica (NMO), and in age and gender-matched controls.

Methods

We tested sera from NMO patients or controls by Western blotting. We also tested sera for its ability to neutralise epsilon toxin in a cell culture system.

Results

Using Western blotting 50% of samples in the NMO group (n=30) reacted with epsilon toxin monomer or dimer. In the control group (n=20), 5% of the samples reacted. However, we also found reactivity with a band at approximately 50kDa in all groups. We are currently working to identify this 50kDa molecule. None of the sera we tested were able to neutralise epsilon toxin activity towards chinese hamster ovary cells expressing myelin and lymphocyte protein.

Conclusions

Our findings provide evidence that epsilon toxin is involved in the development of NMO. Further work is now required to test a larger cohort of NMO patients and controls and to establish whether epsilon toxin is present in the gut of NMO patients during episodes of disease.

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Metabolomics Poster Presentation

P0530 - Understanding the metabolic profile of relapses in multiple sclerosis (ID 326)

Speakers
Presentation Number
P0530
Presentation Topic
Metabolomics

Abstract

Background

Accurate determination of relapses in multiple sclerosis (MS) is important for subtype classification and therapeutic decisions. However, there are currently no validated bio-fluid markers of relapses.

Objectives

To determine if metabolic perturbations are present during relapses, and if so, to identify candidate metabolite biomarkers and evaluate their discriminatory value both at group and individual levels, in comparison with serum neurofilament-light (NfL).

Methods

Global and targeted serum high resolution 1H nuclear magnetic resonance metabolomics and serum NfL (Simoa® assay) were performed on 4 groups of relapsing-remitting MS (RRMS) patients; (1) in relapses (in-R), (2) last relapse (LR) ≥1 month (M) to <6 M ago, (3) LR ≥6 M to <24 M ago, and (4) LR ≥24 M ago. Supervised multivariate analyses were used to determine metabolic differences between patient groups.

Results

Two hundred and one RRMS patients were recruited; in-R (n=38), LR 1–6 M (n=28), LR 6–24 M (n=34), LR ≥24 M (n=101). The global metabolic profile of in-R was significantly perturbed compared to LR ≥24 M (mean predictive accuracy ± SD, 62.6 ± 4.8% vs. 50.9 ± 8.2%; p <0.0001). Identified discriminatory metabolites were quantified, when possible, using targeted metabolomics. Lysine (high in-R), asparagine (high), isoleucine (low) and leucine (low) were shortlisted as potential metabolite biomarkers. One-way ANOVA of these metabolites showed significant differences across the 4 patient groups, with a clear trend (increasing or decreasing) with time away from relapse. Multivariable receiver operating characteristics (ROC) analysis of these 4 metabolites in discriminating in-R vs. LR ≥24 months showed an area under the curve (AUC) of 0.758, while serum NfL had an AUC of 0.575. Within individual patients (n=9) with paired relapse-remission samples (remission sample taken within 6 months of relapse), all 4 metabolites were significantly different in relapse and in remission, with directions consistent with that observed at group level, while serum NfL was not significant. Multivariable ROC of the 4 metabolites showed an AUC of 0.911. At group level, lysine and asparagine were higher in patients with gadolinium enhancing lesions in the last 1 year prior to sampling. No potential confounders were identified on further analyses, notably; none of in-R was on steroids at blood sampling.

Conclusions

Metabolomics identify perturbations in metabolites relating to energy deficiency and immune activation in relapses, and the use of these metabolites, singly or in combination, are useful in identifying relapses, both at group and individual level.

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Imaging Poster Presentation

P0557 - Characterizing 1-year development of cervical cord atrophy across different MS phenotypes: a voxel-wise, multicenter analysis (ID 1115)

Abstract

Background

In multiple sclerosis (MS) the cervical spinal cord is often affected by demyelination and neuro-axonal injury, leading to irreversible tissue loss.

Objectives

To use voxel-wise analysis to evaluate the distribution and changes over time of cervical cord atrophy in MS patients from a multicentre dataset acquired at 7 European sites.

Methods

Baseline and 1-year 3D T1-weighted cervical cord scans and clinical evaluation were obtained from 54 healthy controls (HC) and 110 MS patients (13 clinically isolated syndromes [CIS], 75 relapsing-remitting [RR] and 22 progressive [P]MS). A pipeline optimized for longitudinal analysis was used to co-register baseline and 1-year follow-up cervical cord scans to a cord template, obtained by averaging straightened HC images from all centers. Voxel-wise differences of cervical cord atrophy, their longitudinal changes and correlations with clinical variables were assessed using SPM12 and full factorial models (sex-, age-, center- and total cord volume-corrected).

Results

Compared to HC, MS patients exhibited significant (p<0.05, family-wise error [FWE] corrected) baseline cervical cord atrophy, mainly located in anterior, posterior and lateral cord regions at C1/C2, as well as in posterior regions between C4 and C6. While CIS patients showed a slight cord tissue expansion vs HC at posterior C4, RRMS presented significant clusters of cord atrophy vs CIS, mostly in lateral and posterior C2-C4 regions, and PMS showed widespread cord atrophy vs RRMS patients at C4-C5 and C7 levels. During the follow-up, a significant progression (p<0.05, FWE) of cord atrophy was detected in MS patients, predominantly in the posterior and lateral cord at C2, and between C4 and C6. Such pattern of cord atrophy progression was mainly driven by RRMS patients, while CIS patients did not show cord tissue loss at follow-up vs baseline, and PMS patients showed circumscribed tissue loss in posterior regions at C2 and C6. A strong relationship (p<0.05, FWE) was found between baseline clinical disability and baseline cord atrophy in the posterior and lateral cord at C2-C4. Also, baseline atrophy in the lateral cord at C3-C4 correlated with clinical disability at 1-year follow-up.

Conclusions

Voxel-wise analysis of cervical atrophy allowed to detect a differential involvement of cord levels and to characterize 1-year evolution of tissue loss across phenotypes. Cord atrophy was clinically relevant and contributed to explain follow-up clinical disability.

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Neuromyelitis Optica and Anti-MOG Disease Poster Presentation

P0692 - Benefit of eculizumab for a broad range of patients with aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder: findings from PREVENT (ID 408)

Abstract

Background

Antibodies to the aquaporin-4 (AQP4) water channel in neuromyelitis optica spectrum disorder (NMOSD) are reported to trigger the complement cascade, which is implicated in neuronal injury. The terminal complement inhibitor eculizumab is the first treatment approved for use in patients with AQP4 immunoglobulin G-positive NMOSD, based on PREVENT data.

Objectives

To determine whether the beneficial effect of eculizumab in reducing relapse risk in patients with NMOSD is associated with time since diagnosis, relapse history, disability burden or prior immunosuppressant therapy (IST) use, based on data from the phase 3 trial PREVENT (NCT01892345)

Methods

In PREVENT, patients received eculizumab (maintenance dose, 1200 mg/2 weeks) or placebo, with stable-dose concomitant IST (except rituximab and mitoxantrone) permitted. PREVENT was not powered for subgroup analyses; post hoc descriptive analysis was performed on subgroups defined by time since diagnosis, total number of historical relapses, baseline Expanded Disability Status Scale (EDSS) score and prior IST use.

Results

The proportions of patients experiencing an adjudicated relapse were lower with eculizumab than with placebo in all subgroups. Proportions for eculizumab and placebo, respectively, were: 2/31 versus 6/12 for < 1 year since diagnosis and 1/65 versus 14/35 for ≥ 1 year since diagnosis; 1/39 versus 10/24 for 2–4 historical relapses and 2/57 versus 10/23 for ≥ 5 historical relapses; 0/14 versus 3/6 for baseline EDSS scores ≤ 2.0 and 3/82 versus 17/41 for baseline EDSS scores ≥ 2.5 to ≤ 7.0; 0/15 versus 2/5 for no prior IST use (except corticosteroids alone); and 3/81 versus 18/42 for prior IST use. Relapse-risk reductions were consistent and statistically significant in all subgroups.

Conclusions

The data from this post hoc subgroup analysis suggest that eculizumab reduced relapse risk in PREVENT compared with placebo, regardless of time since NMOSD diagnosis, relapse history, disability burden or prior IST use.

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Neuromyelitis Optica and Anti-MOG Disease Poster Presentation

P0718 - Impact of relapse on disability and quality of life in patients with neuromyelitis optica spectrum disorder: findings from the Phase 3 PREVENT study (ID 701)

Speakers
Presentation Number
P0718
Presentation Topic
Neuromyelitis Optica and Anti-MOG Disease

Abstract

Background

Neuromyelitis optica spectrum disorder (NMOSD) is a rare, inflammatory disorder associated with relapse activity that may lead to poor recovery. The phase 3 PREVENT study was a randomized controlled trial with an open-label extension (OLE) that evaluated the efficacy of eculizumab in patients with aquaporin-4 immunoglobulin G-positive (AQP4-IgG+) NMOSD. Patients on eculizumab had a significantly lower risk of adjudicated relapse versus patients on placebo and reported improved health-related quality of life (HRQoL). Additional analyses on the impact of relapses on disease progression can provide a basis for the strategic treatment of patients with NMOSD.

Objectives

A post hoc analysis of data from the PREVENT study and its OLE assessed the impact of relapses on disability and HRQoL in patients with AQP4-IgG+ NMOSD.

Methods

Neurological disability was measured via the Expanded Disability Status Scale (EDSS). HRQoL was assessed using the Physical Component Summary (PCS) and Mental Component Summary (MCS) of the 36-Item Short-Form Health Survey (SF-36). Changes in mean scores and the proportion of patients having clinically meaningful worsening (SF-36: 5-point decrease; EDSS: ≥2-point increase if the baseline score was 0, ≥1-point increase if the baseline score was 1 to 5, and ≥0.5-point increase if the baseline score was ≥5.5) from prerelapse to 30, 90, and 120 days post relapse were analysed.

Results

Overall, 27 patients were identified as having ≥1 adjudicated relapse. Compared with prerelapse measures, mean SF-36 PCS and MCS scores were significantly worse at 30 days post relapse, the mean EDSS score was significantly worse at 90 days post relapse, and the mean score for the SF-36 MCS was significantly worse at 120 days post relapse. Between 30 and 90 days post relapse, the proportion of patients with clinically meaningful worsening increased by 7%, 8%, and 11% for the EDSS, SF-36 PCS, and SF-36 MCS, respectively. Between 90 and 120 days post relapse, the proportion of patients decreased by 11% for the EDSS to reach 30%, and increased only by 4% for both the SF-36 PCS and SF-36 MCS to reach 31% and 50%, respectively, suggesting a stabilization of the relapse symptoms.

Conclusions

In the PREVENT study and its OLE, patients with AQP4-IgG+ NMOSD had significant, sustained (120 days) worsening of disability and HRQoL outcomes following adjudicated relapses. One-quarter to one-half of relapsing patients experienced stable, clinically meaningful worsening.

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Neuromyelitis Optica and Anti-MOG Disease Poster Presentation

P0727 - Long-term efficacy and safety of eculizumab in AQP4+ neuromyelitis optica spectrum disorder (ID 555)

Speakers
Presentation Number
P0727
Presentation Topic
Neuromyelitis Optica and Anti-MOG Disease

Abstract

Background

Neuromyelitis optica spectrum disorder (NMOSD) relapses can cause significant and irreversible neurologic disability. In PREVENT, eculizumab reduced the risk of relapse in patients with aquaporin-4 immunoglobulin G-positive (AQP4+) NMOSD by 94.2% vs placebo (hazard ratio 0.058; 95% confidence interval [CI]: 0.017–0.197; p < 0.0001) and adjudicated annualized relapse rate (ARR) for eculizumab was 0.02. The rate of adverse events (AEs)/100 patient-years (PY) was 749.3 for eculizumab and 1160.9 for placebo.

Objectives

To present the long-term efficacy and safety of eculizumab in patients with AQP4+ NMOSD during PREVENT (NCT01892345) and its ongoing open-label extension (OLE; NCT02003144).

Methods

During PREVENT, adults with AQP4+ NMOSD received eculizumab (maintenance dose, 1200 mg/2 weeks) or placebo with/without concomitant immunosuppressive therapy (IST). Patients who completed PREVENT could enroll in the OLE to receive eculizumab. Eculizumab safety and efficacy data from PREVENT and its OLE (interim data cut, July 31, 2019) were combined for this analysis.

Results

Overall, 137 patients received eculizumab, and were observed for a median (range) of 133.29 (5.1– 276.9) weeks, for a combined total of 362.3 PY. The estimated percentage of patients who were relapse free at 192 weeks (3.7 years) was 94.4% (95% CI: 88.6–97.3). The adjudicated ARR was 0.025 (95% CI: 0.013–0.048) and the annualized relapse-related hospitalization rate (ARRHR) was 0.03/PY (95% CI: 0.017–0.055). Rates of AEs and serious AEs (SAEs)/100 PY were 732.5 and 33.7, respectively. Common AEs included headache (29.2%) and upper respiratory tract infection (27.7%). Common SAEs, excluding NMOSD relapses, were pneumonia (3.6%), urinary tract infection (2.9%) and acute cholecystitis (2.9%). One patient died during PREVENT (pulmonary empyema) and one patient developed a disseminated Neisseria gonorrhoeae infection. In all, 25/137 patients (18.2%) developed a serious infection vs 6/47 (12.8%) receiving placebo in PREVENT. No patient had a meningococcal infection. During the OLE, 50/119 patients (42%) changed concomitant IST; most patients (44/50) stopped or decreased concomitant IST dose.

Conclusions

During PREVENT and its OLE, the percentage of relapse-free patients remained high (94%) through 192 weeks. Eculizumab was well tolerated and AEs were consistent with the safety profile established in other indications. ARRHR was low and many patients were able to reduce or stop concomitant IST.

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Neuromyelitis Optica and Anti-MOG Disease Poster Presentation

P0754 - Satralizumab in first incident treatment-naïve AQP4-IgG seropositive NMOSD patients enrolled to SAkuraStar: a case series (ID 1371)

Speakers
Presentation Number
P0754
Presentation Topic
Neuromyelitis Optica and Anti-MOG Disease

Abstract

Background

Patients with neuromyelitis optica spectrum disorder (NMOSD) may experience severe disability after their incident (first) attack, with disability accumulating with subsequent relapses. Satralizumab, a humanized monoclonal antibody that inhibits the interleukin-6 receptor, reduced relapse frequency and had a favorable safety profile vs placebo in two randomized, placebo-controlled, phase 3 clinical trials in patients with NMOSD: SAkuraSky (satralizumab in combination with baseline immunosuppressants; NCT02028884), and SAkuraStar (satralizumab monotherapy; NCT02073279).

Objectives

To review a case series of treatment-naïve, aquaporin-4-IgG seropositive (AQP4-IgG+) NMOSD patients who enrolled in SAkuraStar following their incident attack.

Methods

All instances of investigator-reported relapse were assessed in six treatment-naïve, AQP4-IgG+ NMOSD patients enrolled in SAkuraStar after their first attack. Relapses that met protocol-defined relapse (PDR) criteria are specified. Patients who experienced a PDR or remained in SAkuraStar when the double-blind period ended were eligible to enter the open-label extension (OLE). Expanded Disability Status Scale (EDSS) scores were recorded at regular intervals and at relapse.

Results

Of the six enrolled patients, two were randomized to placebo, and four to satralizumab. Demographic characteristics in these six patients were generally consistent with the overall SAkuraStar population. One of the two patients who received placebo experienced a PDR on Study Day 21, with a 1.5-point increase in EDSS score, and fully recovered to pre-relapse EDSS score. Two of the four patients who received satralizumab experienced a relapse. The first patient experienced a PDR on Study Day 214, with a 1-point increase in EDSS, and the second patient experienced a relapse (not meeting PDR criteria) on Study Day 458, with a 0.5-point increase in EDSS score. Both patients fully recovered to pre-relapse EDSS score.

Five of six patients continued in the ongoing OLE, and no further relapses were reported (up to March 2020). Safety outcomes were consistent with the overall SAkuraStar safety population.

Conclusions

Treatment-naïve AQP4-IgG+ patients enrolled in SAkuraStar after their incident attack and randomized to placebo experienced a relapse earlier than those randomized to satralizumab. All patients fully recovered to pre-relapse EDSS score. Interpretation is limited due to the small sample size.

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Neuromyelitis Optica and Anti-MOG Disease Poster Presentation

P0761 - What is seronegative neuromyelitis optica spectrum disorder? (ID 1160)

Speakers
Presentation Number
P0761
Presentation Topic
Neuromyelitis Optica and Anti-MOG Disease

Abstract

Background

Most but not all cases of Neuromyelitis Optica Spectrum Disorder (NMOSD) are associated with Aquaporin-4 (AQP4) or myelin oligodendrocyte glycoprotein (MOG) antibodies.

Objectives

To determine the core clinical characteristics of seronegative NMOSD patients fulfilling 2015 International Diagnostic consensus criteria, treated in the National NMOSD service.

Methods

Retrospective review of patient databases at The Walton Centre for Neurology and Neurosurgery and The John Radcliffe Hospital (Neuromyelitis Optica National Referral Centres) between 1st January 2010 - 17th January 2020.

Results

Of NMOSD=727, 49(7%) were seronegative. The male to female ratio was 1:2.5 and median age at onset was 36(5-57) years. In 2/3 of patients the index presentation was myelitis=22 or myelitis+optic neuritis=11. In 26/33 (79%), longitudinally extensive myelitis was present. Optic neuritis=9 (4 bilateral) and brain involvement=7 were also seen. Relapsing disease was observed in 39/49(80%) of patients. The median annualised attack rate was 0.58 over a median disease duration of 78 (3-258) months. Unmatched CSF oligoclonal bands (CSF-OCBs) were detected in 4/38(11%) and 31/49(63%) fulfilled multiple sclerosis (MS) diagnostic criteria. Immunosuppression (typically Mycophenolate and Rituximab) was used in 34/49(69%). Median last EDSS was 4 (1-10) with death recorded in 5/49 (10%) patients.

Conclusions

Seronegative NMOSD is uncommon. Longitudinal myelitis with/without optic neuritis is a common initial presentation. Similar to AQP4-IgG, NMOSD disability and mortality rates are high. Absence of unmatched CSF-OCB and typical brain lesions help to distinguish this disease from MS.

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Invited Presentations Invited Abstracts

TC03.02 - 2 Antibody Neg Nmo like Syndromes: Unravelling the Diagnosis and How to Manage Them (ID 593)

Speakers
Authors
Presentation Number
TC03.02
Presentation Topic
Invited Presentations

Presenter Of 1 Presentation

Invited Presentations Invited Abstracts

TC03.02 - 2 Antibody Neg Nmo like Syndromes: Unravelling the Diagnosis and How to Manage Them (ID 593)

Speakers
Authors
Presentation Number
TC03.02
Presentation Topic
Invited Presentations

Moderator Of 1 Session

Teaching Course Fri, Sep 11, 2020
Session Type
Teaching Course
Date
Fri, Sep 11, 2020

Invited Speaker Of 1 Presentation

Invited Presentations Invited Abstracts

TC03.02 - 2 Antibody Neg Nmo like Syndromes: Unravelling the Diagnosis and How to Manage Them (ID 593)

Speakers
Authors
Presentation Number
TC03.02
Presentation Topic
Invited Presentations