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Clinical and MRI outcomes from ASCLEPIOS and ALITHIOS were analysed in patients receiving Ofatumumab (OMB) during the core and extension (OMB-OMB) and patients who switched from Teriflunomide (TER) to OMB in the extension (TER-OMB). Of the 1882 patients randomized, 946/936 received OMB/TER and 690/677 continued/were switched to OMB in the extension.Switching from TER to OMB in the extension significantly reduced the ARR by 68.3–76.6%; continuing OMB in the extension further reduced ARR by 39.9–65.1%. Within the prior DMT subgroups, the lowest mean ARR was achieved in patients in the OMB-OMB group with ≤1 DMT (0.046–0.049). Switching to/continuing OMB was associated with a consistent numerical reduction in the risk of 3/6mCDW with the greatest benefit observed in patients on continuous OMB with ≤1 DMT or ≤40 years old. The almost complete suppression of T1 Gd+ activity seen in those randomised to OMB in the core was mirrored in the TER-OMB groups in the extension (90.00–100% across all prior DMT and age subgroups) and sustained in the OMB-OMB group. New/enlarging T2 lesions showed a similar, though delayed, suppression in the TER-OMB group.Switching from TER to OMB in ALITHIOS reduced clinical and MRI disease activity across all prior DMT and age subgroups.

Confirmed disability worsening (CDW), progression independent of relapse activity (PIRA), relapse-as- sociated worsening (RAW), and brain volume change (BVC) was assessed in relapsing multiple sclerosis patients receiving ofatumumab for up to 5 years from the ASCLEPIOS + ALITHIOS open-label extensionOf 1882 patients randomized in ASCLEPIOS I/II (ofatumumab/teriflunomide:946/936), 1367 entered ALITHIOS (continuous/switch:690/677). Most patients were free from 3m/6mCDW events during the studies (ofatu- mumab: 85.0%; teriflunomide: 80.7%). Up to 4 years (cut off: 25-Sep-2021), 119/946 (12.6%) and 148/936 (15.8%) patients had 6mCDW in the continuous and switch groups, respectively. In the continuous group, the 6mPIRA Kaplan-Meier cumulative event rate [KM-CER] remained low (11.0%) and 6mPIRA accounted for most patients, i.e., 86/119 (72.3%; core:65.9%; extension:92.9%) whereas 6mRAW (KM-CER: 3.5%) accounted for only 30/119 (25.2%) patients (core:30.8%; extension:7.1%). Up to 4 years, overall mean PBVC remained low, –1.42% and –1.62% for the continuous and switch groups, respectively (at week 240). ABVC for continuous ofatumumab remained low in the core (–0.34%/year) and extension (–0.28%/year). In the switch group, ABVC was –0.42%/year(core) and –0.29%/year(extension).With longer-term ofatumumab treatment, disability progression was predominantly PIRA, the annual rate of BVC remained low, and low rates of CDW/PIRA indicated that most patients remained free from disease progression.

Objective Subcutaneous ocrelizumab is being developed to provide treatment flexibility and additional choice to patients with multiple sclerosis. OCARINA I (NCT03972306) is an open‐label, multicenter, Phase 1b, dose‐finding study to investigate the pharmacokinetics, safety, tolerability, and immunogenicity of subcutaneous ocrelizumab and to select a dose for the Phase 3 OCARINA II study (NCT05232825). Methods Patients with relapsing or primary progressive multiple sclerosis (aged 18–65 years; Expanded Disability Status Scale score 0.0–6.5) were enrolled into two groups: previously treated with intravenous ocrelizumab (Group A) or naïve to ocrelizumab (Group B). Patients received single ascending doses of subcutaneous ocrelizumab up to 1200 mg. Following dose escalation, new patients in Group A were randomized (1:1) to receive a single 600 mg intravenous ocrelizumab dose or the candidate subcutaneous dose, which was predicted to result in similar exposure as the 600 mg intravenous dose while being safe and well tolerated. The area under the concentration–time curve for both formulations was used to select the subcutaneous ocrelizumab dose. Patients in all cohorts could enter a dose‐continuation phase. Results Eighty‐eight and 47 patients were enrolled into Group A and B, respectively; most patients were female (72.7%/63.0%), and mean age at baseline was 45.7 and 39.7 years, respectively. Subcutaneous ocrelizumab was well tolerated across all doses tested. The 920 mg subcutaneous ocrelizumab dose was selected for the OCARINA II study based on pharmacokinetic and safety data. Interpretation Subcutaneous ocrelizumab may provide patients with multiple sclerosis with an additional treatment option.

In two parallel randomized trials in patients with MS, ublituximab resulted in lower relapse rates and fewer brain lesions on MRI than teriflunomide over a period of 96 weeks but did not affect disability.

Neuro-Behçet disease (NBD) is a multisystem inflammatory disorder characterized by oral lesions, genital lesions, uveitis, and neurological deficits. If left untreated, it may lead to worsening neurological function and can be fatal. Here we present a case of a 52-year-old woman who was diagnosed with Behçet disease (BD) as a teenager and had a relatively mild disease course. Decades later after her initial DB diagnosis, she presented to our hospital with a chief complaint of headache. She did not have focal neurological deficits or any active mucosal lesions. Upon further investigation, the patient was found to have multiple inflammatory changes on neuroimaging and abnormal cerebrospinal fluid (CSF), consistent with the diagnosis of NBD. She was treated with intravenous corticosteroid therapy and her symptoms resolved. Although our patient presented with minimal symptoms decades after her initial diagnosis, any neurological complaint warranted a thorough investigation for a proper diagnosis and treatment given the multisystem involvement of BD.

The majority of deep learning models in medical image analysis concentrate on single snapshot timepoint circumstances, such as the identification of current pathology on a given image or volume. This is often in contrast to the diagnostic methodology in radiology where presumed pathologic findings are correlated to prior studies and subsequent changes over time. For multiple sclerosis (MS), the current body of literature describes various forms of lesion segmentation with few studies analyzing disability progression over time. For the purpose of longitudinal time-dependent analysis, we propose a combinatorial analysis of a video vision transformer (ViViT) benchmarked against traditional recurrent neural network of Convolutional Neural Network–Long Short-Term Memory (CNN-LSTM) architectures and a hybrid Vision Transformer-LSTM (ViT-LSTM) to predict long-term disability based upon the Extended Disability Severity Score (EDSS). The patient cohort was procured from a two-site institution with 703 patients’ multisequence, contrast-enhanced MRIs of the cervical spine between the years 2002 and 2023. Following a competitive performance analysis, a VGG-16-based CNN-LSTM was compared to ViViT with an ablation analysis to determine time-dependency of the models. The VGG16-LSTM predicted trinary classification of EDSS score in 6 years with 0.74 AUC versus the ViViT with 0.84 AUC (p-value < 0.001 per 5 × 2 cross-validation F-test) on an 80:20 hold-out testing split. However, the VGG16-LSTM outperformed ViViT when patients with only 2 years of MRIs (n = 94) (0.75 AUC versus 0.72 AUC, respectively). Exact EDSS classification was investigated for both models using both classification and regression strategies but showed collectively worse performance. Our experimental results demonstrate the ability of time-dependent deep learning models to predict disability in MS using trinary stratification of disability, mimicking clinical practice. Further work includes external validation and subsequent observational clinical trials.

The goal of this study was to evaluate clinical outcomes and patient-reported outcomes (PROs) over 12 months in patients with relapsing multiple sclerosis (RMS) who switched from glatiramer acetate (GA) to delayed-release dimethyl fumarate (DMF) 240 mg BID after suboptimal response to GA in real-world clinical practice. The RESPOND (Effectiveness of DMF and Its Impact on PROs in Suboptimal GA Responders With RMS) study was a Phase IV, prospective, multicenter, open-label, single-arm, 12-month observational trial. The study was conducted in the United States at 63 sites between August 2013 and February 2016. Patients diagnosed with RMS who experienced a suboptimal response to GA (defined as perceived suboptimal efficacy, intolerance, or poor adherence to GA) were eligible for enrollment. DMF treatment was initiated within 60 days of enrollment. The primary objective was to estimate the annualized relapse rate (ARR) at 12 months based on data collected from medical records and compare it with the 12 months before DMF initiation. Secondary objectives of the study included assessing the change in PRO scores from baseline to 12 months; PROs were recorded before and at 6 and 12 months after DMF initiation. Of the 318 patients included in the analysis population, 247 (78%) completed treatment. Mean (SD) time on GA treatment before switching to DMF was 51.3 months (49.1 months). The ARR (95% CI) reported for the 12 months before DMF initiation was 0.49 (0.42–0.57) compared with 0.11 (0.07–0.17) at 12 months after DMF initiation, representing a 78% reduction in ARR (P < 0.0001). Statistically significant improvements from baseline were observed for multiple PROs, including the 36-item Short Form Health Survey physical and mental component summaries (P = 0.0201 and P = 0.0014, respectively), the 5-item Modified Fatigue Impact Scale (P = 0.0002), the 14-item Treatment Satisfaction Questionnaire for Medication (P < 0.0001), and the 7-item Beck Depression Inventory (P = 0.0117). DMF may be an effective treatment option in patients with RMS who experience a suboptimal response to GA. The results should be interpreted with caution due to the observational nature of the study and the lack of a control group. Other limitations of the study include a potential bias due to regression to the mean and lack of randomization. ClinicalTrials.gov identifier: NCT01903291.

ObjectiveTo assess the long-term efficacy of ofatumumab treatment for up to ~4 years in patients with relapsing multiple sclerosis (RMS).MethodsThis analysis (data cut-off: 25-Sep-2021) will include cumulative data from patients randomised to ofatumumab/teriflunomide in the ASCLEPIOS I/II trials (core study) and the ongoing, open-label, ALITHIOS extension study. Patients will be analyzed in two groups: those randomised to ofatumumab in the core (continuous group) and those randomised to teriflunomide in the core with potential switch to ofatumumab in the extension (switch group). Annualised relapse rate (ARR), disability worsening (time- to-3-month/6-month confirmed disability worsening), disability improvement (time-to-6-month confirmed disability improvement), and brain MRI outcomes (number of Gd+T1 lesions and annualised T2 lesion rate) will be assessed.ResultsOverall, 1882 patients who were randomised in the ASCLEPIOS I/II trials (ofatumumab/terifluno- mide: 946/936) will be included in the analysis. In total, 690/946 patients treated with ofatumumab and 677/936 patients treated with teriflunomide entered ALITHIOS. Updated efficacy results for up to ~4 years will be presented at the congress.ConclusionsThese analyses will provide insights on the sustained efficacy of continuous ofatumumab treatment for up to 4 years in patients with RMS, and on ofatumumab efficacy in patients newly switched from teriflunomide. Funding: Novartis Pharma AG, Basel, Switzerland.

Background Multiple sclerosis (MS) is a chronic, inflammatory, central nervous system demyelinating disease that requires long-term use of disease-modifying therapies (DMT). Patient adherence to DMT is key in reducing the inflammation that leads to relapses and neurodegeneration. Dimethyl fumarate (DMF) poses unique challenges to adherence including being the only twice-daily dosing DMT. Previous research suggests there are direct roles that providers play on improving their patients’ adherence rates, such as focusing on the patient-provider relationship, helping put the patient at ease so that they feel understood and respected. Also, route of administration affects adherence in other chronic healthcare conditions. However, the issue of adherence to DMT in MS is more complex than just route of administration, with adverse effects being the main predictor of adherence. Objectives (1) To define various patient specific factors (e.g. fatigue and mood disorders) that affect adherence with DMF and (2) to understand how patients’ perceptions of treatment satisfaction (such as effectiveness, convenience, side effects and global satisfaction) and DMFs impact on quality of life (such as social support, activities of daily living, coping) influence adherence. Methods Our study was a prospective, observational measurement of adherence to treatment with DMF in MS patients over 52 weeks. Twenty-five out of thirty-five patients enrolled completed the study. Adverse event (AE) data was reviewed on all participants. Results Adherence rates correlated with patient’s perceived effectiveness (0.25, p  < 0.023) and the level of bothersome symptoms the patient experienced (0.45, p  < 0.0001). The majority of new AE onset was reported within 12 weeks of DMF initiation. This is consistent with previously published data with DMF use. Conclusion Adherence rates are an important factor to be considered when starting patients on DMT. DMF creates its own barriers to adherence with our study highlighting some, including twice-daily dosing and AEs experienced following treatment initiation. Healthcare providers should be aware of these barriers prior to treatment initiation and counsel patients appropriately.