Klinikum rechts der Isar, Technical University of Munich

Author Of 2 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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Author Of 5 Presentations

Diagnostic Criteria and Differential Diagnosis Poster Presentation

P0263 - Serum neurofilament predicts clinical progression and increases diagnostic accuracy in patients with early multiple sclerosis (ID 1336)

Abstract

Background

Up to date prognostic estimation in newly diagnosed patients is hardly possible while the differentiation between disabling versus more benign courses is of utmost relevance. Reliable blood-based biomarkers that are associated with diagnosis and prognosis of multiple sclerosis (MS) have not been established.

Objectives

Can serum neurofilament light chain measurements serve as a reliable biomarker for diagnostic accuracy and prognosis for multiple sclerosis patients at the time point of diagnosis?

Methods

In a multicenter prospective longitudinal observational cohort, patients with a first diagnosis of multiple sclerosis (MS) or clinically isolated syndrome (CIS) were recruited between August 2010 and November 2015 in 22 centers and assessed yearly with a standardized protocol. Patients were offered standard immunotherapies according to national treatment guidelines. Serum NfL concentrations were measured using an ultrasensitive single-molecule array (Simoa).

Results

A possible association between sNfL levels and clinical diagnosis, relapses, MRI parameters and treatment decisions was tested in 814 patients classified according to current (2017) and older (2010) McDonald criteria at time point of diagnosis and two years after study inclusion sNfL levels correlated with number of T2 and Gd+ lesions and clinical relapses. After reclassification of CIS[2010] patients with existing CSF analysis, according to 2017 criteria, sNfL levels were lower in CIS[2017] than RRMS[2017] patients (9.1 pg/ml, IQR 6.2-13.7 pg/ml, n = 45; 10.8 pg/ml, IQR 7.4-20.1 pg/ml, n = 213; p = 0.036) and increased accuracy of distinction between CIS and RRMS, when including ≥ 90th percentile of sNfL values. Patients receiving disease-modifying treatment (DMT) during the first two years had higher sNfl baseline levels (11.8 pg/ml, 7.5-20.9 pg/ml, n = 727) than patients never receiving DMT (9.5 pg/ml, IQR 6.4-14.1 pg/ml, n = 87, p = 0.002). Longitudinal sNfL levels reflected treatment decisions within the first four years.

Conclusions

sNfL is associated with diagnosis and prognosis of MS patients at the time point of first diagnosis and may be of use for initial treatment stratification.

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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

P0742 - Pain, depression and quality of life in NMOSD: a cross-sectional study of 166 AQP4-antibody seropositive patients in Europe (ID 1645)

Abstract

Background

“Spinal pain”, girdle-like dysesthesia, and painful spasms were noted already in earliest disease descriptions in the 18th century. Nowadays it has become clear that pain is a frequent and one of the most disabling symptoms in these patients. Due to the rarity of NMOSD most previous studies of pain and depression were relatively small or included a mixed population AQP4-IgG-seropositive and seronegative patients, while recent clinical trials clearly indicate that pathogenetic mechanisms are different in these forms.

Objectives

To evaluate prevalence, clinical characteristics and predictive factors of pain, depression and their impact on the quality of life (QoL) in a large European seropositive neuromyelitis optica spectrum disease (NMOSD) cohort.

Methods

We included 166 patients with aquaporin-4-seropositive NMOSD from 13 tertiary referral centers of Neuromyelitis Optica Study Group (NEMOS). Clinical data, including expanded disability status scale and localization of spinal lesions on MRI, were retrieved from the NEMOS database or local electronic patient records. Data on pain, depression and quality of life were captured by self-reporting questionnaires.

Results

125 (75.3%) patients suffered from chronic NMOSD-associated pain. Of these, 65.9% had neuropathic pain, 68.8% reported spasticity-associated pain and 26.4% painful tonic spasms. Number of previous myelitis attacks (OR 1.27, p=0.018) and involved upper thoracic segments (OR 1.31, p=0.018) were the only predictive factors for chronic pain. Interestingly, the latter was specifically associated with spasticity-associated (OR 1.36, p=0.002), but not with a neuropathic pain. 39.8% suffered from depression (moderate to severe in 51.5%). Pain severity (OR 1.81, p<0.001) and especially neuropathic character (OR 3.44, P<0.001) were strongly associated with depression. 70.6% of patients with moderate or severe depression and 42.5% of those with neuropathic pain had no specific medications. 64.2% of those under symptomatic treatment still reported moderate to severe pain. Retrospectively, 39.5% of pain-sufferers reported improvement of pain after start of immunotherapy: 37.3% under rituximab, 40.0% under azathioprine, 33.3% under mycophenolate mofetil and 66.7% under tocilizumab. However, there was no difference in terms of pain prevalence or intensity in patients with different immunotherapies. Pain intensity, walking impairment and depression could explain 56% of the physical QoL variability, while depression was the only factor, explaining 46% of the mental QoL variability.

Conclusions

Myelitis episodes involving upper thoracic segments are main drivers of pain in NMOSD. Although pain intensity was lower than in previous studies, pain and depression remain undertreated and strongly affect QoL. Interventional studies on targeted treatment strategies for pain are urgently needed in NMOSD.

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Presenter Of 1 Presentation

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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