Akerhus University Hospital
Neurology

Author Of 5 Presentations

Biomarkers and Bioinformatics Poster Presentation

P0037 - Change in serum neurofilament light chain levels: ENSEMBLE 1-year interim results (ID 945)

Speakers
Presentation Number
P0037
Presentation Topic
Biomarkers and Bioinformatics

Abstract

Background

Early treatment of multiple sclerosis (MS) provides significant long-term benefits. The aim of the Phase IIIb ENSEMBLE study (NCT03085810) is to evaluate the effectiveness and safety of ocrelizumab (OCR) in patients with early-stage relapsing-remitting MS (RRMS). Neurofilament light chain (NfL) is a marker of neuroaxonal injury. OCR reduced elevated NfL levels in patients with relapsing MS and primary progressive MS to those of healthy donors in the OPERA and ORATORIO studies over 96 weeks. NfL levels are assessed yearly in ENSEMBLE.

Objectives

To report 1-year NfL analyses from ENSEMBLE.

Methods

Treatment-naive patients with a diagnosis of early-stage RRMS (age, 18–55 years inclusive; Expanded Disability Status Scale [EDSS] score ≤3.5) per 2010 revised McDonald criteria and a disease duration from the first documented clinical attack consistent with MS disease of ≤3 years and ≥1 clinically reported relapse or ≥1 sign of MRI activity within 12 months of enrollment were included. Patients will receive OCR 600 mg every 24 weeks (first dose, 2×300 mg separated by 14 days) for the 192-week treatment period (maximum 8 doses). Serum NfL levels are measured via the Simoa Quanterix Advantage kit.

Results

A total of 582 patients were included in the NfL evaluation (female, 64.3%; mean [SD]: age, 32.4 [9.2] years; baseline EDSS, 1.70 [0.96]; time since MS symptom onset, 1.08 [0.84] years) with characteristics comparable with the overall population (N=678). The median serum NfL level at baseline was 13.20 pg/mL; 81.8% of patients had levels greater than healthy donors (HDs; 7.1 pg/mL). Median NfL levels at baseline in patients stratified by age, gender and EDSS score were consistent with those of the overall population. The highest median NfL levels at baseline were observed in patients with T1-weighted contrast-enhancing lesions (CELs) at screening (18.71 pg/mL; n=260) and relapses within 3 months of enrollment (14.91 pg/mL; n=217). At Week 48 the median serum NfL level was reduced to 6.35 pg/mL; 60.8% of patients had levels comparable to or lower than the HD level. Decreases in median serum NfL levels were observed, independent of the baseline demographics and disease characteristics of age, gender, EDSS score, CELs, relapses and reason for enrollment.

Conclusions

NfL levels at baseline and patterns of change over 48 weeks were in line with previous evaluations and decreased considerably after 1 year of treatment with ocrelizumab.

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Clinical Trials Poster Presentation

P0220 - Ocrelizumab Phase IIIb efficacy: 1-year NEDA rates (with MRI re-baselining) from the ENSEMBLE study in early-stage relapsing-remitting MS patients (ID 849)

Abstract

Background

Early treatment of multiple sclerosis (MS) has been shown to provide significant long-term benefits in terms of Expanded Disability Status Scale (EDSS) score versus delayed treatment (patients switching from placebo to active treatment). ENSEMBLE (NCT03085810) is a Phase IIIb study evaluating the effectiveness and safety of ocrelizumab (OCR) in patients with early-stage relapsing-remitting multiple sclerosis (RRMS). Assessments of effectiveness in ENSEMBLE include composite endpoint measures, e.g. the proportion of patients with no evidence of disease activity (NEDA).

Objectives

To report ENSEMBLE 1-year interim NEDA rates.

Methods

Treatment-naive patients with a diagnosis of early-stage RRMS (age, 18–55 years inclusive; EDSS score ≤3.5) per 2010 revised McDonald criteria and a disease duration from the first documented clinical attack consistent with MS disease of ≤3 years and ≥1 clinically reported relapse or ≥1 sign of MRI activity within 12 months of enrollment were included. Patients received OCR 600 mg every 24 weeks (first dose 2×300 mg separated by 14 days) throughout the 192-week (4-year) treatment period (max 8 doses). Clinical assessments will be conducted every 24 weeks. NEDA is defined as absence of: protocol-defined relapses (PDRs), 24-week confirmed disability progression (24W-CDP), T1-weighted contrast-enhancing (CEL) and new/enlarging T2-weighted (T2w) lesions. The effects of OCR are not immediate. MRI measures were re-baselined at Week 8 (prespecified) so that the calculation of NEDA would reflect a more accurate treatment effect.

Results

A total of 678 patients (female, 64.6%) were enrolled (74.6% of patients based on the presence of reasons of both MS relapse and MRI activity) and analyzed. Baseline demographics and disease characteristics reflected a population with early-stage disease (mean [SD]: age, 32.4 [9.1] years; baseline EDSS, 1.71 [0.95]; time since RRMS diagnosis, 0.36 [0.40] years; time since MS symptom onset, 1.10 [0.84] years). At Week 48 most patients (84.8% [n/N=545/643]) reached NEDA. Most patients were free of PDR (98.1%), 24W-CDP (94.1%), CEL (94.2%; re-baselined) and new/enlarging T2w (95.2%; re-baselined) lesions. NEDA calculated without MRI re-baselining was achieved by 62.1% of patients (n/N=404/651). Safety results were consistent with prior studies.

Conclusions

In ENSEMBLE, the Year 1 NEDA rate with MRI re-baselining was high (84.8%) in patients with early-stage disease. No new safety signals were observed.

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Disease Modifying Therapies – Risk Management Poster Presentation

P0392 - Shorter infusion time of ocrelizumab: results from the ENSEMBLE PLUS study in patients with relapsing-remitting multiple sclerosis (ID 900)

Speakers
Presentation Number
P0392
Presentation Topic
Disease Modifying Therapies – Risk Management

Abstract

Background

Ocrelizumab (OCR) is an intravenously administered anti-CD20 antibody approved for relapsing and primary progressive multiple sclerosis (MS). Shortening the infusion duration to 2hrs reduces the total site stay (including mandatory pre-medication/infusion/observation) from 5.5–6hrs, to 4hrs, which may reduce patient and site staff burden.

Objectives

ENSEMBLE PLUS aims to investigate the safety and tolerability of OCR when administered over a shorter infusion time.

Methods

ENSEMBLE PLUS is a randomized, double-blind substudy to the ENSEMBLE study (NCT03085810). In ENSEMBLE, treatment-naïve patients with active, early-stage relapsing-remitting MS (18–55 years; disease duration ≤3 years; EDSS score 0–3.5) receive OCR 600mg infusions every 24 weeks for 192 weeks. In ENSEMBLE PLUS, OCR (600mg) administered over the approved infusion time (3.5hrs; conventional duration), was compared with a 2hr infusion (shorter duration); the infusion duration of the initial 2×300mg dose was unaffected. The frequency and severity of infusion-related reactions (IRRs) were assessed during and 24hrs post-infusion. The ENSEMBLE PLUS primary endpoint was the proportion of patients with IRRs at the first Randomized Dose.

Results

In total, 373 and 372 patients were randomized to the conventional and shorter infusion groups, respectively. At the first Randomized Dose, 99 patients (26.5%) in the conventional and 107 (28.8%) in the shorter infusion group had IRRs (difference in proportions, stratified estimates [95% CI]: 2.4% [-3.8, 8.7]); most common symptoms during the infusion were throat irritation, dysphagia and ear pruritus, whilst 24hrs post-infusion were fatigue, headache and nausea. IRRs led to infusion slowing/temporary interruption in 22 patients (5.9%) in the conventional and 39 (10.5%) in the shorter infusion group. The majority of IRRs were mild or moderate. Across all Randomized Doses, four severe (Grade 3) IRRs occurred in total, one in the conventional and three in the shorter infusion group. Overall, >99% of IRRs resolved without sequelae in both groups. No IRRs were serious, life-threatening or fatal; no IRR-related discontinuations occurred. Adverse events (AEs) and serious AEs were consistent with the known OCR safety profile.

Conclusions

Frequency and severity of IRRs were similar between conventional and shorter infusions. No new safety signals were detected. Shorter ocrelizumab infusions reduce the infusion site stay, thus may reduce patient and staff burden.

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Epidemiology Poster Presentation

P0500 - The impact of seasonal fluctuations of vitamin D on long-term disability progression in MS (ID 1353)

Abstract

Background

Vitamin D is associated with inflammatory activity in MS, but it is less clear whether seasonal fluctuations of vitamin D levels can affect long-term prognosis in MS.

Objectives

We examined whether seasonal fluctuations of serum vitamin D levels were associated with long-term (10 years) disability scores in a well-defined group of adult Norwegian MS patients.

Methods

A cohort of 80 patients with relapsing-remitting MS completed a randomized controlled study on ω-3 fatty acids between 2004 and 2008. During the study period of 24 months, serum 25-hydroxyvitamin D (25[OH]D) were measured at 9 time points: at baseline, and then at month 1, 3, 6, 7, 9, 12, 18, and 24. A mean value per season (summer, fall, winter, spring) was calculated from these values. In 2017, a follow-up study was conducted, including disability assessment by the Expanded Disability Status Scale (EDSS). In linear regression models, we explored the association between dichotomized values of 25(OH)D (“above median” and “below median”) per season and the change in EDSS score 10 years later.

Results

The highest 25(OH)D levels were seen during summer (June-August: mean = 85.9 nmol/L, median = 81.0 nmol/L) when solar radiation peaks in Norway, and the lowest 25(OH)D levels were seen during spring (March-May: mean 55.8 nmol/L, median = 52.5 nmol/L). Higher 25(OH)D levels during winter, spring, and summer were significantly associated with less disability progression after 10 years in separate models adjusted for age, sex, and baseline EDSS score. However, in a model mutually adjusted for 25(OH)D levels for all four seasons, only spring levels remained significantly associated with disability progression. In this model, the EDSS change was 0.71 point (95% CI: 0.02 to 1.40) lower for patients with above compared to below median spring levels. The effect estimate remained similar after further adjusting for disease duration and disease-modifying treatment.

Conclusions

In our study population, low vitamin D levels during spring were significantly associated with greater long-term disability progression. This finding suggests that vitamin D supplements may be of extra importance during this season.

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Reproductive Aspects and Pregnancy Poster Presentation

P1129 - Peripartum depression and anxiety in women with MS. A population-based cohort study. (ID 305)

Speakers
Presentation Number
P1129
Presentation Topic
Reproductive Aspects and Pregnancy

Abstract

Background

People with multiple sclerosis (MS) have increased risk of depression and anxiety. It is not known if pregnancy and birth impact the risk of psychiatric symptoms in women with MS.

Objectives

To assess the occurrence, risk factors and prognosis of peripartum depression and anxiety in women with MS before and after diagnosis.

Methods

This study included women from the prospective Norwegian Mother, Father and Child Cohort study (MoBa) between 1999-2008. We used data from questionnaires at gestational weeks 18 and 30, and at 6 and 18 months postpartum. Self-reported data on depression and anxiety were recorded by Hopkins Symptom Checklist. Identification of women with MS was obtained from the Norwegian MS Registry, Norwegian Patient Registry and hospital records. The identified MS-women (n=546) were divided into 1) Pre-birth diagnosis (n=140), 2) Pre-birth onset with post-birth diagnosis (n=98) and 3) Post-birth onset (n=308). Thirty-five women were diagnosed with MS in the postpartum period. In group 2 and 3 the median follow-up time from birth until diagnosis was 7 years (range 0-17). The reference group consisted of women in MoBa without MS (n=111,267).

Results

Depression in gestational week 30 was more common among women with pre-birth diagnosis compared to the reference group (15% vs. 9%, OR 2.0 95% CI 1.2-3.1), adjusted for age, parity, overweight, socioeconomic factors and clustering among siblings. For those depressed in this group, the symptoms more often persisted to 6 months postpartum (77% vs. 38%, p=0.004), but the prognosis 18 months postpartum was similar. Women who were diagnosed with MS in the postpartum period had higher occurrence of depression compared to the reference group both 6 months (23% vs. 10%, p=0.023) and 18 months postpartum (42% vs. 13%, p<0.001). There was no significant difference in peripartum depression in women with post-birth diagnosis (group 2 and 3) compared to the reference group. Risk factors associated with depression in women with pre-birth diagnosis were adverse socioeconomic factors, history of physical and/or sexual abuse and pre-pregnancy psychiatric disease. There was no difference in peripartum anxiety between any of the MS groups and the reference group.

Conclusions

Women with diagnosed MS have an increased risk of depression in the third trimester. The burden of having a MS diagnosis seems to be the determinant for depression. Clinicians should be aware of postpartum depression in women diagnosed with MS in this period.

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