Author Of 3 Presentations
P0263 - Serum neurofilament predicts clinical progression and increases diagnostic accuracy in patients with early multiple sclerosis (ID 1336)
- S. Bittner
- F. Steffen
- T. Uphaus
- M. Muthuraman
- V. Fleischer
- A. Salmen
- F. Luessi
- A. Berthele
- L. Klotz
- S. Meuth
- A. Bayas
- F. Paul
- H. Hartung
- R. Linker
- C. Heesen
- M. Stangel
- B. Wildemann
- F. Then Bergh
- B. Tackenberg
- T. Kuempfel
- F. Weber
- U. Zettl
- U. Ziemann
- H. Tumani
- S. Groppa
- M. Mühlau
- C. Lukas
- B. Hemmer
- H. Wiendl
- R. Gold
- F. Zipp
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.
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?
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).
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 patients with existing CSF analysis, according to 2017 criteria, sNfL levels were lower in CIS than RRMS 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.
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.
P0916 - Safety and tolerability in patients with multiple sclerosis receiving ocrelizumab in a real-world setting – CONFIDENCE one-year interim analysis (ID 1136)
As of April 2020, >160,000 patients with relapsing forms of multiple sclerosis (RMS) or primary progressive MS (PPMS) worldwide had started treatment with ocrelizumab (OCR), a humanized monoclonal antibody selectively targeting CD20+ B-cells.
Pivotal studies established the risk-benefit profile of OCR under controlled trial conditions.
Real-world data are needed to further characterise the safety of OCR in clinical practice. Here we present 1-year, real-world safety data for patients receiving OCR.
CONFIDENCE (ML39632, EUPAS22951), a non-interventional, post-authorization safety study, aims to enrol 3,000 patients with RMS or PPMS newly treated (up to 30 days prior or 60 days after enrolment) with OCR and 1,500 patients newly treated with other selected DMTs according to label at ~250 German neurological practices. Each patient is followed for 7.5–10 years. Study visits, documented circa every 6 months, follow routine clinical practice. The primary outcome is the incidence and type of uncommon adverse events (AEs) (incidence of 0.1% to 1% [1 to 10 out of 1000 patients] or less). Statistical analyses are mainly descriptive and exploratory. Assessments of effectiveness (secondary objectives) are presented separately.
As of 30 June 2020, 2,129 patients treated with OCR had been recruited. The interim analysis is expected to include approximately 559 OCR-treated patients, ~82% with RMS and ~18% with PPMS, with 1-year follow-up data (mean baseline age [SD], 45.5 [11.4] years; 64.4% female; mean baseline EDSS [SD] RMS 3.3 [1.9], PPMS 4.5 [1.7]). Preliminary data showed that ~63.0% of patients had ≥1 AE during OCR treatment; ~26.8% had treatment-related AEs (TRAEs). The most common AEs were infections and infestations (~31.5%), nervous system disorders (~14.7%), and general disorders and administration site conditions (~12.3%). The incidence of serious AEs was ~14.0%, most frequently infections and infestations (~3.6%; RMS, ~3.9% [n=18]; PPMS, ~1.9% [n=2]), nervous system disorders (~3.2%), and injury, poisoning and procedural complications (~2.1). The most frequent serious infections were urinary tract infections (~1.3% [n=7]) and pneumonia (~0.5% [n=3]). Seven patients overall (1.3%) had treatment-related serious infections.
The safety profile of OCR in this first interim analysis of the CONFIDENCE study, representing a real-world population currently treated with OCR in Germany, was consistent with controlled clinical trials.
P1123 - Gender dimorphism of hippocampal intrinsic networks and regional integrity in multiple sclerosis (ID 1743)
The hippocampus is a complex anatomical structure with a fine-tuned intrinsic network architecture, shaped by functional and structural compartmentalization. The hippocampus is affected early in multiple sclerosis (MS) and besides focal neuroinflammatory damage, network disruption is thought to account for cognitive deficits in MS. Given the sex-related vulnerability to cognitive decline in MS, sex-driven differences in hippocampal networks and regional integrity can be hypothesized.
To characterize sex effects on hippocampal network organization and subfield integrity, and their relation to cognitive performance.
In a cohort of 476 MS patients (age 35±10 years), 337 females and 139 males with a disease duration of 16±14 months were imaged on a 3T MRI scanner at baseline and after 2 years. A control group of healthy subjects (HS, n=110, age 34±15 years, 54 females) was included. Volumes of 12 hippocampal subfields were quantified and fed into the reconstruction of the single-subject morphometric networks and analyzed within the graph theoretical framework. Sex-related differences in network and subfield properties were evaluated with linear mixed-effects models, adjusted for age, center and total hippocampal volume; p-values are reported after Bonferroni correction for multiple comparisons.
At baseline, both female and male patients displayed higher clustering (p<0.05) compared to HS. Female patients had higher clustering (p<0.05) but equally efficient network organization (local and global efficiency, p>0.05) compared to male patients. At follow-ups, independently of sex, patients had increased modularity, clustering and global efficiency, however, with higher values in female patients (all p<0.05). Both female and male patients had lower volumes in almost all subfields compared to HS. Female patients had smaller parasubiculum and presubiculum but larger molecular layer as compared to male patients. Over time, female patients had more widespread regional volumetric reduction compared to male patients. Cognitive performance was positively associated with clustering (r=0.27, p<0.01), local (r=0.25, p<0.01) and global efficiency (r=0.24, p<0.01) only in female but not in male patients.
Our findings suggest a more clustered and modular network architecture in female patients despite a more extensive local atrophy over time. The stronger association of cognitive performance with intrinsic hippocampal connectivity may explain cognitive reserve in female patients. These results may serve for sex-targeted neuropsychological interventions.