University Hospital Münster
Department of Neurology with Institute of Translational Neurology

Author Of 2 Presentations

Imaging Poster Presentation

P0599 - Linking microstructural integrity and motor cortex excitability in multiple sclerosis (ID 1151)

Speakers
Presentation Number
P0599
Presentation Topic
Imaging

Abstract

Background

Motor skills are commonly impaired in patients with multiple sclerosis (MS) as a consequence of gray (GM) and white matter (WM) pathology and cortical excitability abnormalities.

Objectives

We hypothesized that microstructural characteristics of motor regions as assessed with the neurite orientation dispersion and density imaging (NODDI) model predict motor cortical excitability that is frequently altered in MS. Further, we evaluated pathological microstructure alterations in motor WM tracts of MS patients compared to healthy controls (HC) using NODDI in comparison to the diffusion tensor imaging (DTI) parameter fractional anisotropy (FA).

Methods

We applied advanced diffusion imaging in 50 MS patients and 49 age-matched HC. As excitability maker, we assessed resting motor thresholds using non-invasive transcranial magnetic stimulation. For quantification of microstructural integrity of the motor system, neurite density index (NDI), orientation dispersion index (ODI), isotropic volume fraction (IVF) and FA averaged within left primary motor cortex as the stimulation site were considered. We applied hierarchical regression modeling to evaluate the prediction of the resting motor threshold by NDI, ODI, IVF and FA in MS patients and HC. Cognitive-motor performance quantified by the Nine Hole Peg Test and Trail Making Test part A (TMT-A) and part B (TMT-B) was regressed on the diffusion parameters in a subsample of 44 MS patients. In the WM, we applied tract-based spatial statistics with the threshold-free cluster enhancement (TFCE) method within motor tracts comparing MS patients and HC. We tracked contributions of NDI and ODI to FA and evaluated if the NODDI model detects additional pathological alterations.

Results

A hierarchical regression revealed that lower NDI suggestive for axonal loss in the GM significantly predicted higher motor thresholds, i.e. reduced excitability in MS patients (F(1,48) = 7.493, p = .009). Lower NDI was indicative for decreased performance in TMT-A (F(1,42) = 8.102; p = .007) and TMT-B (F(1,42) = 7.390; p = .009). Microstructural abnormalities of the interconnected WM tracts were characterized by lowered FA, decreased NDI and increased ODI in MS (all TFCE-corrected p < .05). NDI exclusively (56%) and in overlap with FA (19%) accounted for the largest amount of differences, followed by ODI alone (9%).

Conclusions

Our work shows that lower neurite density in primary motor cortex is linked to decreased motor cortical excitability and decreased cognitive-motor performance in MS patients. Lower neurite density and higher orientation dispersion are characteristic in the WM of MS patients compared to HC. Our results suggest that these markers are more sensitive to pathological alterations than the classical DTI measure FA. This work outlines the potential of microstructure imaging using advanced biophysical models to forecast neurodegeneration and excitability alterations in neuroinflammation.

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Patient-Reported Outcomes and Quality of Life Poster Presentation

P1063 - Treatment persistence and adherence to Ocrelizumab in the real-world setting- an ad-hoc analysis of the CONFIDENCE study (ID 1731)

Speakers
Presentation Number
P1063
Presentation Topic
Patient-Reported Outcomes and Quality of Life

Abstract

Background

Ocrelizumab (OCR) is a humanised anti-CD20+ monoclonal antibody approved for the treatment of relapsing and primary progressive forms of multiple sclerosis (RMS and PPMS). Real-world evidence on adherence and persistence with OCR is limited.

Objectives

To examine the persistence and adherence to OCR in a real-world setting.

Methods

CONFIDENCE (ML39632, EUPAS22951) is an ongoing non-interventional, post-authorization safety study, aiming to enroll 3,000 patients newly treated with OCR and 1,500 patients newly treated with other DMTs at ~250 centers in Germany. Follow up regardless of discontinuation of treatment will be for up to 10 years. In this ad-hoc analysis of CONFIDENCE, persistence and adherence were measured exclusively for patients treated with OCR with at least one post-initiation (i.e., first two 300mg doses IVs') assessment visit. Persistence was examined as a survival function of event-free time from discontinuation. Patients were considered at-risk until the last assessment visit recorded prior to data cut-off (31 March 2020) or censored at time of OCR discontinuation, whichever occurred first. Adherence was assessed using median time intervals between infusions.

Results

Overall, 1614 patients treated with OCR were included in this analysis; 1296 patients with RMS and 318 with PPMS. Median [IQR] age at OCR initiation was 42 [44, 57] years and 52 [33, 51] years in patients with RMS and PPMS, respectively. Most RMS patients were females (66.7%) while gender distribution in PPMS patients was approximately equal (51.6% females). Median [IQR] disease duration from diagnosis up to OCR initiation was longer in RMS (7.9 [3.0, 14.7] years) than in PPMS patients (3.4 [0.8, 9.7] years). Median [IQR] EDSS at OCR start was 3.0 [2.0, 4.5] and 4.5 [3.5, 6.0] in the RMS and PPMS population, respectively. At data cut-off, the median [IQR] OCR exposure duration was 7.85 [5.5, 13.1] months for RMS and 6.87 [0.5, 12.5] months for PPMS patients. Overall, the median time between infusions ranged from 5.9 and 6.0 months and did not differ between RMS and PPMS cohorts. Treatment persistence at 18 months was 96.6% (95% CI: 95.3-97.8%) and very consistent between RMS and PPMS patients.

Conclusions

Adherence to disease-modifying therapy (DMT) is critical for achieving therapeutic goals in MS. This analysis shows high treatment persistence for OCR patients at 18 months and strong adherence to recommendations to administer OCR infusions every 24 weeks.

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Presenter Of 1 Presentation

Patient-Reported Outcomes and Quality of Life Poster Presentation

P1063 - Treatment persistence and adherence to Ocrelizumab in the real-world setting- an ad-hoc analysis of the CONFIDENCE study (ID 1731)

Speakers
Presentation Number
P1063
Presentation Topic
Patient-Reported Outcomes and Quality of Life

Abstract

Background

Ocrelizumab (OCR) is a humanised anti-CD20+ monoclonal antibody approved for the treatment of relapsing and primary progressive forms of multiple sclerosis (RMS and PPMS). Real-world evidence on adherence and persistence with OCR is limited.

Objectives

To examine the persistence and adherence to OCR in a real-world setting.

Methods

CONFIDENCE (ML39632, EUPAS22951) is an ongoing non-interventional, post-authorization safety study, aiming to enroll 3,000 patients newly treated with OCR and 1,500 patients newly treated with other DMTs at ~250 centers in Germany. Follow up regardless of discontinuation of treatment will be for up to 10 years. In this ad-hoc analysis of CONFIDENCE, persistence and adherence were measured exclusively for patients treated with OCR with at least one post-initiation (i.e., first two 300mg doses IVs') assessment visit. Persistence was examined as a survival function of event-free time from discontinuation. Patients were considered at-risk until the last assessment visit recorded prior to data cut-off (31 March 2020) or censored at time of OCR discontinuation, whichever occurred first. Adherence was assessed using median time intervals between infusions.

Results

Overall, 1614 patients treated with OCR were included in this analysis; 1296 patients with RMS and 318 with PPMS. Median [IQR] age at OCR initiation was 42 [44, 57] years and 52 [33, 51] years in patients with RMS and PPMS, respectively. Most RMS patients were females (66.7%) while gender distribution in PPMS patients was approximately equal (51.6% females). Median [IQR] disease duration from diagnosis up to OCR initiation was longer in RMS (7.9 [3.0, 14.7] years) than in PPMS patients (3.4 [0.8, 9.7] years). Median [IQR] EDSS at OCR start was 3.0 [2.0, 4.5] and 4.5 [3.5, 6.0] in the RMS and PPMS population, respectively. At data cut-off, the median [IQR] OCR exposure duration was 7.85 [5.5, 13.1] months for RMS and 6.87 [0.5, 12.5] months for PPMS patients. Overall, the median time between infusions ranged from 5.9 and 6.0 months and did not differ between RMS and PPMS cohorts. Treatment persistence at 18 months was 96.6% (95% CI: 95.3-97.8%) and very consistent between RMS and PPMS patients.

Conclusions

Adherence to disease-modifying therapy (DMT) is critical for achieving therapeutic goals in MS. This analysis shows high treatment persistence for OCR patients at 18 months and strong adherence to recommendations to administer OCR infusions every 24 weeks.

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