University of Catania
Department "GF Ingrassia", Section of Neurosciences

Author Of 3 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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Imaging Poster Presentation

P0636 - Relationship of real-world brain atrophy to MS disability using icobrain: 4 centre pilot study (ID 716)

Abstract

Background

To date, no studies have explored the relationship between brain atrophy and MS disability using differing MRI protocols and scanners at multiple sites.

Objectives

To assess the association between brain atrophy and MS disability, as measured by EDSS and 6-month confirmed disability progression (CDP).

Methods

In this retrospective study at 4 MS centres, a total of 1300 patients had brain MRI imaging assessed by icobrain. Relapse-onset MS patients were included if they had two clinical MRIs 12 (±3) months apart and ≥2 EDSS scores post MRI-2, the first ≤3 months from MRI-2, with ≥6 months between first and last EDSS. Volumetric data were analysed if the alignment similarity between two images was as good as that of same-scanner scan-rescan images (normalised mutual information ≥0.2). The percentage brain volume change (PBVC), percentage grey matter change (PGMC), FLAIR lesion volume change, whole brain volume, grey matter volume, FLAIR lesion volume and T1 hypointense lesion volume at MRI-2 were calculated. Ordinal mixed effect models were used to determine the association between these volumetric MRI measures and all EDSS scores post MRI-2. Cox proportional hazards models were used for the 6-month CDP outcome, using a subset of patients with ≥3 EDSS. Models were adjusted for proportion of time spent on disease-modifying therapy during MRIs ± whole brain/grey matter volume at baseline MRI.

Results

Of the 260 relapse-onset MS patients included, 204 (78%) MRI pairs were performed in the same scanner and 56 (22%) pairs were from different scanners. During the follow-up period (median 3.8 years, range 1.3-8.9), 29 of 244 (12%) patients experienced 6-month CDP. There was no evidence for association between annualised PBVC or PGMC and CDP or EDSS (p>0.05). Cross-sectional whole brain and grey matter volume (at MRI-2) tended to associate with CDP (HR 0.99, 95% CI 0.98-1.00, p=0.06). Every 1ml of whole brain or grey matter volume lost represented a 1% higher chance of reaching 6-month CDP. Only whole brain volume (at MRI-2) was associated with EDSS score (β -0.03, SE 0.01, p<0.001) and the slope of EDSS change over time (β -0.001, SE 0.0003, p=0.02). On average, every 33ml reduction of brain volume was associated with a 1 step increase in EDSS.

Conclusions

In this real-world clinical setting where a fifth of the brain atrophy analysis were performed on different scanners, we found no association between individual brain atrophy and MS disability. However, there was an association between cross-sectional whole brain volume with EDSS and slope of EDSS change.

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Neuromyelitis Optica and Anti-MOG Disease Poster Presentation

P0759 - Treatment patterns in patients with neuromyelitis optica spectrum disorder (ID 1400)

Abstract

Background

Many patients with neuromyelitis optica spectrum disorder (NMOSD) are managed using off-label immunosuppressants for relapse prevention, and treatment guidelines are based on small, often uncontrolled, studies with low levels of evidence.

Objectives

To assess real-world treatment patterns in patients with NMOSD.

Methods

Based on the global NMOBase cohort, patients diagnosed with NMOSD between 2006–2019 per the international 2015 consensus criteria and with ≥2 Expanded Disability Status Scale scores recorded at different visits were included in the study population. The aquaporin-4 autoantibody (AQP4-IgG) serostatus was determined mainly by cell-based assay; treatment sequence for maintenance therapies was assessed in seropositive (AQP4-IgG+) patients only. The date of biomarker testing was used as a proxy for diagnosis date and served as the baseline for the observational period.

Results

The study population included 334 NMOSD patients tested for AQP4-IgG serostatus. Among them, 301 (90.1%) were AQP4-IgG+. Mean age was 45.3 years; 84.1% were women and 51.8% (n=156) came from Europe. Two thirds had ≥5 visits recorded in NMObase, and the mean observational period was 4.8 years. Five treatment lines (1L–5L) were observed, with only 1.3% of the AQP4-IgG+ cohort (n=4) progressing to the last line. At baseline, the most common therapy was azathioprine (23.6%) followed by rituximab (5.3%), and 65.4% (n=197) were not prescribed any disease-modifying therapy (DMT). The median time between the test date and initiation of DMT was 3.2 months, although 25% of patients waited >10 months. Most AQP4-IgG+ patients (66.4%; n=200) progressed beyond 1L. The most frequent treatments at 2L were rituximab (43.5%) and azathioprine (41.0%). The proportion receiving rituximab, the predominant therapy beyond 2L, remained stable at 3L (48.1%; n=25) and 4L (46.7%; n=7). Across all treatment lines, there were anecdotal reports of use of DMT indicated for multiple sclerosis (MS) (e.g., betaferon), possibly reflecting old clinical practice. A large proportion (83.4%) received corticosteroids, either as acute relapse- or maintenance- therapy, along their treatment pathway.

Conclusions

Based on data collected before recent drug approvals, the main treatment options included off-label drugs and a few MS DMTs. A quarter of patients did not initiate NMOSD DMTs for >10 months from diagnosis. Newly approved therapies might partly address this unmet need, at least for AQP4-IgG+ patients.

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