Anthony Traboulsee

Background: Recent research has suggested that rituximab is not non-inferior to ocrelizumab in the treatment of relapsing multiple sclerosis (RMS). We compared the effectiveness of rituximab versus ocrelizumab in RMS. Methods: Individuals with RMS treated with rituximab or ocrelizumab with ⩾12 months of clinical follow-up and/or post-rebaseline magnetic resonance imaging (MRI) data were propensity-scored matched 1:1 and included. Objectives: Primary outcomes were annualized relapse rate (ARR), ARR ratio and cumulative hazard of relapses. The secondary outcome was the proportion of each group demonstrating post-rebaseline radiological activity. Results: In total, 538 individuals were included in the primary (clinical) outcome analysis and 350 individuals were included in the secondary (radiologic) outcome analysis. Over a median 2-year follow-up, very low ARR was observed in both groups (rituximab: 0.05 (95% CI: 0.03–0.08) versus ocrelizumab: 0.03 (95% CI: 0.02–0.05)). The adjusted ARR ratio for rituximab compared with ocrelizumab was elevated at 1.76 (95% CI: 0.70–4.59), and the adjusted cumulative hazard of relapses was also elevated for rituximab-treated individuals (HR = 2.17 (95% CI: 0.91–5.1)). Conclusion: Although our results suggest that rituximab may be inferior to ocrelizumab for relapse suppression, the rarity of relapses underpowered comparisons, and no definitive conclusions could be drawn.

Background/Objectives: Characterizing spinal cord multiple sclerosis (MS) lesions in MRI is critical for diagnosis, monitoring, and treatment evaluation. However, current automated approaches for lesion detection and segmentation are typically designed for specific MRI contrasts or acquisition sites, limiting their generalizability in real-world clinical settings where imaging protocols vary widely. This work proposes a robust multi-site, multi-contrast segmentation framework for spinal cord lesions. Methods: The segmentation model was trained and evaluated on a large-scale dataset comprising 4428 annotated images from 1849 persons with MS across 23 imaging centers, encompassing six MRI contrasts (T1w, T2w, T2*w, PSIR, STIR, and UNIT1) acquired at 1.5 tesla (T), 3 T, and 7 T. Results: Likert-type assessment performed by neuroradiologist ratings demonstrated superior generalization of the model compared to existing contrast-specific pipelines ( p < 0.01). Additional experiments evaluated robustness across spinal levels, acquisition resolutions, binarization thresholds, and quantitative evaluation on external labeled datasets. Conclusions: The proposed model can achieve accurate and reliable spinal cord MS lesion segmentation across heterogeneous MRI data, addressing a key barrier to clinical translation. The model is available in the Spinal Cord Toolbox v7.2 and higher. Code repository: https://github.com/ivadomed/seg-sc-ms-lesion-multicontrast

BACKGROUND AND PURPOSE: Double inversion recovery (DIR) is an MRI technique in which two types of tissue are suppressed, usually cerebrospinal fluid (CSF) and white matter (WM). The suppression is achieved with two inversion pulses prior to the acquisition of the imaging data. In the presence of strong inhomogeneities in the static magnetic field B₀ and/or the radiofrequency (RF) field, inversion may be inadequate, resulting in bright signal in tissues that should have been suppressed. The purpose of this work was to develop a DIR scan with inversion pulses that are robust against inhomogeneities in the B₀ and RF field. MATERIALS AND METHODS: In this prospective study, the DIR sequence was equipped with inversion pulses designed with optimal control. Robustness against field inhomogeneities was incorporated into the cost functional for pulse optimization. DIR and controlled DIR (C-DIR) MRI images were acquired at 3T in 14 participants (9 male, age=36.1±11.5 years) enrolled between October 2024 to August 2025 from a single academic medical center: nine healthy; two with relapsing-remitting multiple sclerosis; one with persistent concussion symptoms; two with asymptomatic white matter hyperintensities. Suppression of CSF, presence of artifacts, and visibility of multiple sclerosis lesions and white matter hyperintensities were independently assessed visually by a radiologist. In eight healthy volunteers, means and SDs were computed for signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR), with significance evaluated using a Student’s t-test. RESULTS: C-DIR exhibits improved inversion in the presence of inhomogeneities in the B₀ and the radiofrequency field, resulting in the removal of artifactual signal. CNR increases ranged from 27% between gray matter and CSF (p<.001) to 102% between the brainstem and adjacent CSF (p<0.001). SNR in the cortical gray matter was 10.74±1.48 in DIR and 11.68±2.21 in C-DIR (p=.07). CONCLUSIONS: Inversion with a robust RF pulse improves the quality of DIR, demonstrating artifact reduction and improved CNR.

Background: Ocrelizumab (OCR) and rituximab (RTX) are anti-CD20 monoclonal antibodies (CD20Mabs) used in the treatment of relapsing multiple sclerosis (RMS). While both are effective at reducing relapses and new MRI lesions in clinical trials, real-world data on discontinuation rates and reasons for stopping therapy are limited. Methods: This observational retrospective chart review included patients from two MS clinics in British Columbia, Canada. RMS patients treated with at least one infusion of OCR or RTX between January 2017 and March 2023 were included. Primary outcomes were reasons for discontinuation and discontinuation rates, with a secondary outcome of time to discontinuation. Results: In total, 881 RMS patients were included, with 478 on OCR and 403 on RTX. A total of 16.9% of patients on OCR and 14.9% on RTX discontinued therapy over 1643 and 694 patient-years, respectively ( p = 0.46). Reasons for discontinuation included: side effects (33.3%), insurance coverage (17.0%) and clinical or radiological disease activity (11.3%). Discontinuation rates at 12, 24 and 36 months were 3.5%, 8.2% and 12.5% for OCR, and 6.4%, 14.8% and 22.2% for RTX, respectively ( p = 0.0089). Median time to discontinuation was 21 months on OCR and 11.5 months on RTX ( p < 0.0001). On Cox regression analysis, treatment with RTX was the only variable associated with discontinuation (hazard ratio 1.72, 95% CI 1.20–2.45). Conclusion: Discontinuation rates of CD20Mabs were low, and the most common reason for stopping was side effects. Although not designed for comparison, our study suggests RMS patients may persist longer on OCR than RTX.

Supplementary Materials and Methods: DAGitty code for Figure 1

Directed acyclic graphs (DAG) are increasingly recognized as powerful tools in research and can be used for elucidating complex causal relationships inherent in cancer development, progression, and treatment outcomes. In oncology, in which multifactorial risk factors are the norm, the ability to visualize and interrogate these relationships is critical. In observational studies, DAGs offer a rigorous framework for identifying confounders, mediators, and colliders, allowing researchers to estimate causal effects. This study presents the development and application of a DAG in a real-world observational study involving skin cancer. We outline practical steps for constructing DAGs and discuss how to use them to select variables that help control for confounding. Our approach provides a valuable guide for oncologists, epidemiologists, and other cancer researchers aiming to enhance the transparency and validity of causal claims across a wide range of oncologic contexts—from prevention and early detection to survivorship and health disparities.