Initiation Of Disease-modifying Therapy Research Articles

Delayed initiation of disease modifying therapy increases relapse frequency and motor disability in pediatric onset multiple sclerosis

ObjectiveTo evaluate association between time to initiation of disease modifying treatment (DMT) and outcomes in pediatric-onset Multiple Sclerosis (POMS). MethodsA retrospective analysis of children with POMS from two tertiary referral pediatric Neuroimmunology clinics. Outcome measures comprised annualized relapse rate (ARR), MRI lesion burden (T1, T2-FLAIR, and post-GAD contrast sequences), EDSS, and 25-ft walk duration at the latest follow-up visit. Univariate and multivariate analysis using linear and logistic regression models were used to assess associations between patient characteristics and outcomes. ResultsIn total, 68 patients were reviewed. More than half of patients were female (62 %) and 32 (47 %) were Hispanic/LatinX. Median age at diagnosis was 14.2 years (IQR: 11.0–16.5), and median duration from diagnosis to the latest follow-up was 2.5 years (IQR: 1.6–4.6). Sensory (29.4 %), brainstem (23.5 %), and pyramidal (19.1 %) symptoms were most common. Interferon beta (32.4 %), dimethyl fumarate (27.9 %) and rituximab (26.5 %) were the most frequently used first-line DMT. Patients had a median ARR of 0.5 (IQR: 0.08–0.84), and EDSS score of 1.0 (IQR: 0.0–2.0) at the most recent follow-up. Delayed DMT initiation correlated with higher ARR (R = 0.38, p = 0.0016) and longer 25-ft walk duration (R = 0.34, p = 0.0077). In multivariate analysis, delayed DMT remained a significant predictor of higher ARR (p = 0.002) and longer 25-ft walk duration (p = 0.047). Delayed DMT initiation and use of low/moderate efficacy DMT predicted GAD enhancing lesions at the latest follow-up (p = 0.004 and 0.019 respectively). ConclusionDelayed DMT initiation in POMS is linked to unfavorable outcomes, including higher ARR and longer 25-ft walk duration.

E010 Impact of rheumatologist ultrasound clinic on the management of inflammatory arthritis at a tertiary centre rheumatology department

Abstract Background/Aims Musculoskeletal ultrasound plays an important role in the assessment and management of inflammatory arthritis, enabling early diagnosis and prompt initiation of disease modifying therapy, as well as escalation of therapy as part of a treat-to-target strategy. It can help clinicians distinguish between true joint inflammation and non-inflammatory causes of increased pain scores. We reviewed our weekly rheumatology ultrasound clinic service where patients are referred to aid in clinical decision making. The study aimed to evaluate the cohort of patients attending the rheumatology ultrasound clinic at University Hospitals of Leicester, a busy tertiary centre, serving a multi-ethnic population, and to assess the impact of this clinic on the management of inflammatory arthritis in these patients. Methods Data was collected retrospectively from the ultrasound clinic at University Hospitals of Leicester between June 2022 and June 2023. Outcome measures included: date of scan request, date of scan, underlying disease, C - reactive protein (CRP), anti-CCP level, presence of radiographic erosions, presence of active synovitis or erosions on ultrasound, other rheumatologic disease and how the ultrasound findings changed the patient’s management. Results The total number of patients attending the clinic during the study period was 91. Of these, 70% were female and 30% male. Over the study period, 11.8% of patients did not attend their appointment. At the time of referral, 68% of patients had a CRP<5, 91% had a negative anti-CCP and 83% had no radiographic erosions. Following the scan, 13% of the patients had active synovitis, and 10% received at least one steroid injection. Interestingly, 86% had no active inflammation and no indication to escalate their disease modifying drug. In our patient cohort, 16% had pre-existing fibromyalgia. In all appointments, the clinician performing the scan showed the ultrasound images to the patient and explained the findings. Conclusion This ultrasound clinic is a key part of the treat-to-target strategy for inflammatory arthritis, enabling escalation of disease modifying therapy where indicated. It allows ultrasound guided and marked injections to be given when needed and identifies patients with non-inflammatory causes of increased pain scores, preventing patients from receiving unnecessary immunosuppression. Disclosure A. Mohammed Murad: None. A. Jubber: None. A. Moorthy: None.

Real-world persistence of multiple sclerosis disease-modifying therapies.

Treatment persistence is the continuation of therapy over time. It reflects a combination of treatment efficacy and tolerability. We aimed to describe real-world rates of persistence on disease-modifying therapies (DMTs) for people with multiple sclerosis (pwMS) and reasons for DMT discontinuation. Treatment data on 4366 consecutive people with relapse-onset multiple sclerosis (MS) were pooled from 13 UK specialist centres during 2021. Inclusion criteria were exposure to at least one MS DMT and a complete history of DMT prescribing. PwMS in blinded clinical trials were excluded. Data collected included sex, age at MS onset, age at DMT initiation, DMT treatment dates, and reasons for stopping or switching DMT. For pwMS who had received immune reconstituting therapies (cladribine/alemtuzumab), discontinuation date was defined as starting an alternative DMT. Kaplan-Meier survival analyses were used to express DMT persistence. In 6997 treatment events (1.6 per person with MS), median time spent on any single maintenance DMT was 4.3 years (95% confidence interval = 4.1-4.5 years). The commonest overall reasons for DMT discontinuation were adverse events (35.0%) and lack of efficacy (30.3%). After 10 years, 20% of people treated with alemtuzumab had received another subsequent DMT, compared to 82% of people treated with interferon or glatiramer acetate. Immune reconstituting DMTs may have the highest potential to offer a single treatment for relapsing MS. Comparative data on DMT persistence and reasons for discontinuation are valuable to inform treatment decisions and in personalizing treatment in MS.

Prediction of disease activity and treatment failure in relapsing–remitting MS patients initiating daily oral DMTs

Background: Limited data exist regarding treatment response prediction to oral disease-modifying therapies (DMTs) in multiple sclerosis (MS). Objectives: We assessed the capacity of available scoring systems to anticipate disease activity parameters in naïve relapsing–remitting MS (RRMS) patients initiating daily oral DMTs, hypothesizing that they exhibit different predictive potentials. Methods: We conducted a retrospective study and applied the Rio Score (RS), modified Rio Score (mRS), and MAGNIMS Score 12 months after DMT initiation. At 36 months, we examined their ability to predict evidence of disease activity (EDA) components and treatment failure by logistic regression analysis. Results: Notably, 218 patients (62.4% females) initiating dimethyl fumarate, teriflunomide, and fingolimod were included. At 36 months, the RS high-risk group predicted evidence of clinical activity (odds ratio (OR) 10 [2.7–36.9]) and treatment failure (OR 10.6 [3.4–32.5]) but did not predict radiological activity (OR 1.9 [0.7–5]). The mRS non-responders group did not predict EDA and treatment failure. RS, mRS, and MAGNIMS 0 categories showed significantly lower EDA and treatment failure than the remainder. Conclusion: Scoring systems present different predictive abilities for disease activity parameters at 36 months in MS patients initiating daily oral therapies, warranting further adjustments (i.e. introduction of fluid biomarkers) to depict disease activity status fully.

Long-Term Disability Outcomes in Relapsing-Remitting Multiple Sclerosis Patients: Impact of Clinical and Demographic Factors on Disease Progression.

Background: Multiple sclerosis (MS) is a prevalent chronic inflammatory and neurodegenerative disease of the central nervous system. The main evolving forms, relapsing-remitting MS (RRMS) and secondary progressive MS (SPMS), lack clear delineation. Methods: We conducted an observational study on 523 Caucasian RRMS patients receiving first-line disease-modifying therapies (DMTs), analyzing demographic, clinical, and geographical data. Results: RRMS patients experienced a statistically significant reduction in relapse rates post-DMT initiation. Significant differences in time to reach an Expanded Disability Status Score (EDSS) of 3.0 and 6.0 were observed based on demographics and onset topography. Kaplan-Meier analysis revealed that the onset with optic or supratentorial symptoms is linked to a longer time until EDSS = 3.0 is reached. Urban origin correlated with a prolonged time until EDSS = 3.0. Gender and environment showed no significant associations with the hazard of reaching an EDSS = 6.0. Cox regression analysis revealed no significant impact of relapses on the time to reach EDSS scores of 3.0 and 6.0 in our study cohort. Conclusions: Multivariate analysis identified several predictive factors for disability progression, including environment, age at onset, and disability level at DMT initiation.

Recent trends in disease-modifying therapy use and associated sickness absence and disability pension among people with multiple sclerosis in Sweden

Background: Disease-modifying therapies (DMTs) have led to improved health and work productivity among people with multiple sclerosis (PwMS). Objectives: To describe trajectories of recent DMT use and their association with sickness absence and/or disability pension (SADP) among PwMS in Sweden. Methods: A longitudinal register–based study was conducted among 1395 PwMS with treatment start in 2014/2015. While DMT use over 5 years was assessed using sequence analysis resulting in four clusters, a 7-year (Y−2 toY4) trend of SADP was analyzed using zero-inflated negative binomial regression. Results: Four clusters of DMT use trajectories were identified: long-term non-high-efficacy (483, 34.6%), long-term high-efficacy (572, 41%), escalation (221, 15.8%), and discontinuation (119, 8.5%). Progressive MS and higher expanded disability status scale scores were associated with the escalation, long-term high-efficacy, or discontinuation clusters. PwMS in the long-term high-efficacy and escalation clusters had higher likelihood of being on SADP. However, PwMS initiating high-efficacy DMTs demonstrated steeper decline in SADP than others. Conclusion: Using sequence analysis, this study showed recent DMT use trajectories among PwMS where initiation of high-efficacy DMTs has become more common. The trend of SADP was stable and lower in those using non-high-efficacy DMTs and larger improvements were shown in those initiating high-efficacy DMTs.

University education facilitates uptake of disease-modifying therapies for multiple sclerosis: A community-based study using the UK MS Register.

Higher education is associated with better job opportunities and higher income. Herein, the impact of education on the uptake of disease-modifying therapies (DMTs) for multiple sclerosis (MS) in a publicly funded health care system was examined using the UK MS Register. All adult participants with relapsing remitting MS diagnosed between 2008 and 2021 were included. Those without data regarding their education levels were excluded. Binary, multinomial and Cox regression models were used to examine the association between education levels and uptake of DMTs. A total of 6317 participants fulfilled all inclusion and exclusion criteria. A total of 1826/2923 (62%) participants with a university education were treated with DMTs, compared to 1788/3394 (53%) participants with school/diploma received DMTs with an odds ratio of 1.318 (1.178-1.473). Participants with a university education were more likely to be treated with both moderate- and high-efficacy DMTs, compared to others, with odds ratios of 1.227 (1.087-1.385) and 1.545 (1.325-1.802), respectively. University education was also a positive predictor for faster initiation of DMTs, and, importantly, higher-efficacy DMTs. In a publicly funded health care system, despite intended equality of access, university education was associated with a higher uptake of DMTs.

Disease-modifying therapy initiation patterns in multiple sclerosis in three large MS populations.

Treatment guidelines recommend early disease-modifying therapy (DMT) initiation after diagnosis of multiple sclerosis (MS). Multinational comparative studies that assess time to DMT initiation in MS may allow detection of barriers inherent to healthcare systems to explain potential adverse systematic delays in commencing DMTs. To investigate and compare the time to first DMT and its association with sociodemographic and clinical variables after MS diagnosis in three large MS registries. This observational study was conducted using data from the German MS Registry (GMSR), the North American Research Committee on MS Registry (NARCOMS, US data only), and the United Kingdom MS Registry (UKMSR, both self- and clinician-reported). Data from relapsing people with MS (PwMS), with a diagnosis of MS between 2014 and 2019, and available DMT and disability status were pooled using a meta-analytic approach. A total of 5395 PwMS were included in the analysis (GMSR: n = 2658; NARCOMS: n = 447; UKMSR: n = 2290). Kaplan-Meier estimates for the time to first DMT [median months (95% CI)] were 2.0 (1.9-2.0), 3.0 (2-4), and 9.0 (7.7-10.6) for GMSR, NARCOMS, and UKMSR, respectively. Pooled multivariable Cox regression demonstrated shorter time to first DMT for PwMS diagnosed after 2017 [1.65 (1.42-1.92), p < 0.01], and longer time to DMT when a higher-efficacy DMT was selected (0.69 (0.54-0.90), p < 0.0001]. Time to DMT initiation differs across the populations studied, indicating that barriers may exist in early access to DMT, particularly in the United Kingdom. However, a consistent decrease in time to DMT initiation was noted since 2017 across all registries. Further studies are warranted comparing the effects of time to DMT and time to higher-efficacy DMT on long-term outcome.

Multiple Sclerosis Progression and Relapse Activity in Children

Although up to 20% of patients with multiple sclerosis (MS) experience onset before 18 years of age, it has been suggested that people with pediatric-onset MS (POMS) are protected against disability because of greater capacity for repair. To assess the incidence of and factors associated with progression independent of relapse activity (PIRA) and relapse-associated worsening (RAW) in POMS compared with typical adult-onset MS (AOMS) and late-onset MS (LOMS). This cohort study on prospectively acquired data from the Italian MS Register was performed from June 1, 2000, to September 30, 2021. At the time of data extraction, longitudinal data from 73 564 patients from 120 MS centers were available in the register. The main outcomes included age-related cumulative incidence and adjusted hazard ratios (HRs) for PIRA and RAW and associated factors. Clinical and magnetic resonance imaging features, time receiving disease-modifying therapy (DMT), and time to first DMT. After applying the inclusion and exclusion criteria, the study assessed 16 130 patients with MS (median [IQR] age at onset, 28.7 [22.8-36.2 years]; 68.3% female). Compared with AOMS and LOMS, patients with POMS had less disability, exhibited more active disease, and were exposed to DMT for a longer period. A first 48-week-confirmed PIRA occurred in 7176 patients (44.5%): 558 patients with POMS (40.4%), 6258 patients with AOMS (44.3%), and 360 patients with LOMS (56.8%) (P < .001). Factors associated with PIRA were older age at onset (AOMS vs POMS HR, 1.42; 95% CI, 1.30-1.55; LOMS vs POMS HR, 2.98; 95% CI, 2.60-3.41; P < .001), longer disease duration (HR, 1.04; 95% CI, 1.04-1.05; P < .001), and shorter DMT exposure (HR, 0.69; 95% CI, 0.64-0.74; P < .001). The incidence of PIRA was 1.3% at 20 years of age, but it rapidly increased approximately 7 times between 21 and 30 years of age (9.0%) and nearly doubled for each age decade from 40 to 70 years (21.6% at 40 years, 39.0% at 50 years, 61.0% at 60 years, and 78.7% at 70 years). The cumulative incidence of RAW events followed a similar trend from 20 to 60 years (0.5% at 20 years, 3.5% at 30 years, 7.8% at 40 years, 14.4% at 50 years, and 24.1% at 60 years); no further increase was found at 70 years (27.7%). Delayed DMT initiation was associated with higher risk of PIRA (HR, 1.16; 95% CI, 1.00-1.34; P = .04) and RAW (HR, 1.75; 95% CI, 1.28-2.39; P = .001). PIRA can occur at any age, and although pediatric onset is not fully protective against progression, this study's findings suggest that patients with pediatric onset are less likely to exhibit PIRA over a decade of follow-up. However, these data also reinforce the benefit for DMT initiation in patients with POMS, as treatment was associated with reduced occurrence of both PIRA and RAW regardless of age at onset.

Blood-based biomarkers in Alzheimer's disease: Future directions for implementation.

Disease-modifying therapies (DMTs) for Alzheimer's disease (AD) will increase diagnostic demand. A non-invasive blood-based biomarker (BBBM) test for detection of amyloid-β pathology may reduce diagnostic barriers and facilitate DMT initiation. To explore heterogeneity in AD care pathways and potential role of BBBM tests. Survey of 213 healthcare professionals/payers in US/China/UK/Germany/Spain/France and two advisory boards (US/Europe). Current diagnostic pathways are heterogeneous, meaning many AD patients are missed while low-risk patients undergo unnecessary procedures. Confirmatory amyloid testing (cerebrospinal fluid biomarkers/positron emission tomography) is utilized in few patients, resulting in diagnostic/treatment delays. A high negative-predictive-value test could streamline the diagnostic pathway by reducing unnecessary procedures in low-risk patients; supporting confirmatory testing where needed. Imminent approval of DMTs will increase need for fast and reliable AD diagnostic tests. An easy-to-use, accurate, non-invasive BBBM test for amyloid pathology could guide diagnostic procedures or referral, streamlining early diagnosis and DMT initiation. This study explored AD care pathways and how BBBM may meet diagnostic demandsCurrent diagnostic pathways are heterogeneous, with country and setting variationsMany AD patients are missed, while low-risk patients undergo unnecessary proceduresAn easy-to-use, accurate, non-invasive BBBM test for amyloid pathology is neededThis test could streamline early diagnosis of amyloid pathology and DMT initiation.

Treatment Patterns by Race and Ethnicity in Newly Diagnosed Persons with Multiple Sclerosis.

Non-Hispanic Black and Hispanic persons with MS (pwMS) are more likely to experience rapid disease progression and severe disability than non-Hispanic White pwMS; however, it is unknown how the initiation of high-efficacy disease-modifying therapies (DMTs) differs by race/ethnicity. This real-world study describes DMT treatment patterns in newly diagnosed pwMS in the United States (US) overall and by race/ethnicity. This retrospective analysis used the US Optum Market Clarity claims/electronic health records database (January 2015-September 2020). pwMS who were first diagnosed in 2016 or later and initiated any DMT in the two years following diagnosis were included. Continuous enrollment in the claims data for ≥ 12 months before and ≥ 24 months after diagnosis was required. Treatment patterns 2 years after diagnosis were analyzed descriptively overall and by race/ethnicity. The sample included 682 newly diagnosed and treated pwMS (non-Hispanic Black, n = 99; non-Hispanic White, n = 479; Hispanic, n = 35; other/unknown race/ethnicity, n = 69). The mean time from diagnosis to DMT initiation was 4.9 months in all pwMS. Glatiramer acetate and dimethyl fumarate were the most common first-line DMTs in non-Hispanic Black (28% and 20% respectively) and Hispanic pwMS (31%, 29%); however, glatiramer acetate and ocrelizumab were the most common in non-Hispanic White pwMS (33%, 18%). Use of first-line high-efficacy DMTs was limited across all race/ethnicity subgroups (11-29%), but uptake increased in non-Hispanic Black and White pwMS over the study period. Use of high-efficacy DMTs was low across all race/ethnicity subgroups of newly diagnosed pwMS in the US, including populations at a greater risk of experiencing rapid disease progression and severe disability.

Short-term brain atrophy evolution after initiation of immunotherapy in a real-world multiple sclerosis cohort.

In multiple sclerosis (MS), brain atrophy measurements have emerged as an important biomarker reflecting neurodegeneration and disability progression. However, due to several potential confounders, investigation of brain atrophy in clinical routine and even in controlled clinical studies can be challenging. The aim of this study was to investigate the short-term dynamics of brain atrophy development after initiation of disease-modifying therapy (DMT) in a "real-world setting." In this retrospective study, we included MS patients starting DMT (natalizumab, fingolimod, dimethyl fumarate, or interferon-ß1a) or without DMT, availability of a baseline MRI, and two annual follow-up scans on the same MRI system. Two-timepoint percentage brain volume changes (PBVCs) were calculated. Fifty-five MS patients (12 patients starting DMT with natalizumab, 7 fingolimod, 14 dimethyl fumarate, 11 interferon-ß1a, and 11 patients without DMT) were included. We found the highest PBVCs in the first 12 months after initiation of natalizumab treatment. Furthermore, the PBVCs in our study were very much comparable to the results observed by other groups, as well as for fingolimod, dimethyl fumarate, and interferon-ß1a. We found PBVCs that are comparable to the results of previous studies, suggesting that brain atrophy, assessed on 3D MRI data sets acquired on the same 3T MRI, provides a robust MS biomarker.

Initiation Patterns of Disease-Modifying Therapies for Multiple Sclerosis Among US Adults and Children, 2001 Through 2020

Many disease-modifying therapies (DMTs) have been approved for multiple sclerosis (MS) in the past 2 decades. Research evaluating how these approvals have changed real-world prescribing patterns is scarce. To evaluate patterns in DMT initiations between 2001 and 2020 among commercially insured US adults and children with MS. This serial cross-sectional study was conducted from 2001 through 2020 (mean patient enrollment duration, 4.8 years) and used US commercial claims data (MarketScan). Analysis took place between January 2022 and March 2023. Of 287 084 patients with MS identified, 113 583 patients (113 095 adults and 488 children) with MS newly initiated at least 1 DMT. New initiation episode of a DMT, defined as no claim for the same DMT in the previous year. The proportion of total DMT initiations per year attributable to each DMT. Trends in initiations were evaluated annually. The study team identified 153 846 DMT initiation episodes among adults (median age, 46 [IQR, 38-53) years]; 86 133 female [76.2%]) and 583 among children (median age, 16 (IQR, 14-17) years; 346 female [70.9%]). Among adults, use of platform injectables showed an absolute decline of 73.8% over the study period, driven by a 61.2% reduction in interferon β initiations (P < .001 for trend). In contrast, the 2010 introduction of oral DMTs led to a rise in their use from 1.1% (2010) to 62.3% (2020) of all DMT initiations (P = .002 for trend). Infusion therapy initiations remained relatively low, accounting for 3.2% of all initiations since their introduction in 2004 but increased modestly annually after ocrelizumab was introduced (2017), reaching 8.2% of all initiations in 2020 (P < .001 for trend). Children showed similar initiation patterns, except for preferred oral therapy. Between 2019 and 2020, dimethyl fumarate was the most commonly initiated DMT in adults (23.3% to 27.2% of all initiations), while in children fingolimod was the most commonly initiated (34.8% to 68.8%). Current MS treatment guidelines emphasize shared decision-making between patients and clinicians to balance treatment efficacy, safety, cost, and convenience. This study found that oral DMTs were the predominant DMT type initiated by 2020. The cause of this shift cannot be determined from this study, but may reflect several factors, including convenience of administration, direct-to-consumer advertising, or insurance restrictions.

Disease Modifying Therapy in Newly Diagnosed People with Multiple Sclerosis – A Real-World Administrative Claims Study (P3-3.017)

<h3>Objective:</h3> To characterize the initial disease modifying therapy (DMT) and time-to-treatment of people who receive a diagnosis of Multiple Sclerosis (MS). <h3>Background:</h3> Initiation of DMT expeditiously after diagnosis is important to reduce disease activity and optimize clinical outcome. MS diagnosis can occur in emergency, inpatient, or outpatient settings so a comprehensive view of subsequent care and treatment can be difficult to ascertain. Administrative claims are a useful tool to observe initiation of care. <h3>Design/Methods:</h3> Longitudinal data of suspected newly diagnosed people with MS (PwMS) from a large payer commercial claims database spanning 2016–2021 were analyzed. Inclusion criteria required any combination of 3 non-overlapping claims with an MS diagnosis (ICD-10-CM: G35) and/or DMT within a year following the first G35. A minimum 5 years of continuous medical and prescription coverage with 2 years prior to and 1 year following the first G35 was required to establish likely initial diagnosis and observe initiation of DMT. Time-to-treatment statistics were calculated for DMTs initiated within a year of the first G35. <h3>Results:</h3> Out of 2,024 cohort members meeting inclusion criteria, 17% started a DMT within 30 days of first MS diagnosis code, and an additional 16% started between 31 and 60 days. 34% of members in this cohort did not have a DMT claim observed in the year following their initial G35. Time-to-treatment varies by DMT. The most frequent therapies initiated within a year were glatiramer acetate, dimethyl fumarate, and ocrelizumab with median (interquartile range) time-to-DMT of 35 (15–70), 47 (22–85), and 79 (51–131) days, respectively. <h3>Conclusions:</h3> Many apparent newly diagnosed PwMS did not start a DMT within a year following the initial MS claim. There is substantial variation in initial DMT and time-to-DMT of those that started within a year. Further study is warranted to understand factors that impact initiation of DMT. <b>Disclosure:</b> Dr. Jordan has received personal compensation for serving as an employee of Octave Bioscience. Dr. Jordan has received personal compensation for serving as an employee of Rally Health/Optum. Dr. Jordan has stock in Octave Bioscience. Dr. Jordan has stock in UnitedHealth Group. Mrs. Hua has received personal compensation for serving as an employee of Octave. Dr. Ghoreyshi has received personal compensation for serving as an employee of Octave Bioscience. Dr. Ghoreyshi has received personal compensation for serving as an employee of Verily Life Sciences. Dr. Ghoreyshi has stock in Octave Bioscience. Dr. Edgeworth has received personal compensation for serving as an employee of Octave Bioscience. Dr. Edgeworth has received personal compensation for serving as an employee of Cigna. Dr. Edgeworth has stock in Octave Bioscience. Dr. Edgeworth has stock in Cigna. Dr. Edgeworth has stock in OnCall Health Corporation, DBA Cayaba Care. Dr. Edgeworth has stock in Winnow AI, Inc. .

Balo’s Concentric Sclerosis presenting as Sensorineural Hearing Loss (P14-3.007)

<h3>Objective:</h3> Multiple sclerosis (MS) can affect other cranial nerves apart from optic nerve. We report an interesting case of Balo’s concentric sclerosis (BCS) that presented with sensorineural hearing loss (SNHL). <h3>Background:</h3> BCS is a rare variant of MS. It derives its name from the concentric pattern of demyelination alternating with preserved myelin seen on magnetic resonance imaging (MRI). It typically has a fulminant monophasic clinical course with a fatal outcome although there has been an increasing number of cases reported with a benign clinical course. <h3>Design/Methods:</h3> NA <h3>Results:</h3> 48-year-old presented to our neuro-immunology clinic for evaluation of abnormal MRI which revealed non-enhancing T2 hyperintensities in juxta-cortical, peri-ventricular and infratentorial cerebellar lesions concerning for demyelination. He had tinnitus and SNHL of right ear ongoing for 3–4 months prior to presentation. Extensive workup was pursued to rule out MS mimics including nutritional, autoimmune, and infectious etiologies. LP revealed no evidence of oligoclonal bands. He was originally diagnosed with radiologically isolated syndrome with plans to monitor with MRI brain annually for surveillance. Repeat MRI brain a year later revealed new non-enhancing concentric juxta-cortical lesion along the right frontal operculum exhibiting a laminated appearance with surrounding perilesional edema consistent with BCS. He had no new neurological symptoms in the interim. On re-evaluation, his auditory symptoms were deemed as a clinical event, and he was diagnosed with MS with subsequent initiation of disease modifying therapy. <h3>Conclusions:</h3> BCS may occur simultaneously with MS like lesions or may herald the onset of MS. SNHL is a rare manifestation of MS with demyelinating lesion along the course of vestibulocochlear nerve or nucleus in brain stem. MRI brain can fail to reveal signs of demyelination either due to timing of MRI brain from symptom onset or sub-optimal diagnostic accuracy as vestibular evoked myogenic potentials have detected demyelinating lesions which are invisible on MRI brain. <b>Disclosure:</b> Dr. Potluri has nothing to disclose. Dr. Samaniego has nothing to disclose. Dr. Lannen has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Genentech. Dr. Lannen has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for TG Therapeutics.

Saudi Consensus Recommendations on the Management of Multiple Sclerosis: Symptom Management and Vaccination

This article deals with recommendations on the management of symptoms of MS and on the provision of vaccinations in patients receiving disease-modifying therapies (DMTs). Symptoms of MS, such as fatigue, depression, urinary symptoms, spasticity, impairment of gait, and sexual dysfunction, are common in this population. Recognizing and addressing these symptoms is key to maintaining the quality of life of people with MS. Vaccination status should be reviewed and updated prior to initiation of DMTs. In general, vaccination should be avoided for variable periods after the initiation of some DMTs. Live attenuated vaccines are contraindicated and should be considered on a case-by-case basis. These consensus recommendations will present the best practices for vaccination in Saudi Arabia before, during, and after the COVID-19 pandemic. The recommendations will be updated periodically and as needed as new evidence becomes available.

Room to improve: The diagnostic journey of Spinal Muscular Atrophy.

To highlight the current diagnostic pathway for children with Spinal Muscular Atrophy (SMA) in Ireland. We look to identify points along the diagnostic pathway that may impede a timely diagnosis, and argue that newborn screening for SMA is the single best measure to remediate these delays. Through retrospective chart review and an online questionnaire, we gathered SMA patient data outlining clinical characteristics and the route to diagnosis of the SMA cohort attending the National SMA Treatment centre at Children's Health Ireland. We found that 32 children were diagnosed with SMA in Ireland in the 15-years from 2007 to 2021, with twelve cases of SMA type I. Muscle weakness is the most commonly reported initial sign, and the GP is usually the first health provider to address parental concerns. Patients commonly experience delays in diagnosis due to factors such as varied SMA clinical phenotypes, and a lack of experience or awareness of SMA amongst community based health care practitioners. In spite of this, when patients do gain early access to tertiary diagnostics through prenatal or neonatal genetic testing, they then report rapid diagnosis and initiation of disease modifying therapy in the crucial pre-symptomatic window. We conclude that delays to diagnosis inherent within the current Irish system are pervasive and arise prior to engagement with tertiary services. All of these delays are remediable through the establishment of a dedicated SMA newborn screening programme.

Association Between Body Mass Index and Response to Disease-Modifying Therapies in Patients With Relapsing-Remitting Multiple Sclerosis at King Abdulaziz University Hospital: A Retrospective Study.

Background Multiple sclerosis (MS) is an immune-mediated inflammatory disease that attacks myelinated axons in the central nervous system, destroying the myelin and axon to varying degrees and producing significant physical disability. So far, many studies have found that having a high body mass index (BMI) is associated with severe autoimmune and neurodegenerative disease course. However, the impact of BMI on disease-modifying therapy (DMT) response in terms of decreasing relapses and improving overall health remains unknown. Aims and objectives The study aimed to demonstrate the effect of BMI on DMT responsiveness in patients with relapse-remitting MS at a tertiary hospital. Methods and material A single-center retrospective study was conducted at a tertiary care center in Jeddah, Saudi Arabia. The study included 89 individuals with relapsing-remitting MS who had their BMI measured within six months of their first clinical relapse, as well as their clinical response to the DMT (number of relapses on a single DMT after six months of initiation) and MRI changes (development of new T2 lesions or gadolinium-enhancing lesions on single DMT six months after DMT initiation). Results Demographic data revealed a female predominance of 71.9%, and 51.7% of the patients had a normal weight. The most commonly prescribed DMT was Gilenya at 47.2%. A significant relationship was found between BMI and the total number of clinical relapses (p=0.038), with the co-existence of a positive correlation between BMI and the number of relapses after at least six months of initiation of DMT. Additionally, MS patients who had both positive MRI changes and obesity had a significantly higher BMI mean than non-obese. Conclusion Increased BMI appeared to be associated with a lower response to DMT, as overweight patients had a worse course than normal and underweight patients. Pharmacokinetic differences are the most likely factors implicated in medication responsiveness.

Roadmap to implementation of a fully automated blood‐based biomarker test to facilitate diagnosis and treatment in early Alzheimer’s disease

AbstractBackgroundRoutine implementation of a fully automated blood based biomarker (BBBM) will expand access to diagnosis and initiation of disease modifying therapies (DMTs) in Alzheimer’s disease (AD). This analysis explores current obstacles in the AD diagnostic pathway, the unmet need for a BBBM test to facilitate referral decisions, and barriers to BBBM testing.MethodData are from quantitative (n=1,694 physicians) and qualitative (n=186 healthcare professionals/payers) surveys in US/China/UK/Germany/Spain and two Advisory Boards (US/Europe). Primary care physicians (PCPs) and specialists (neurologists/geriatricians/psychiatrists) were represented.ResultFrom the quantitative survey, between 17.8% (China) and 83.5% (France) patients with cognitive impairment present first to primary care, with the rest presenting directly to secondary care. 73% PCPs use cognitive assessment alone for referral, with 35% using laboratory results. Confirmatory testing with positron‐emission tomography (PET) or cerebrospinal fluid (CSF) analysis is rare in the primary care setting. PCPs request PET and CSF for 8% and 12% patients, respectively, compared with 40% and 36% for specialist neurologists. Most centers use local guidelines to decide CSF/PET referral. 31% of patients diagnosed with AD underwent CSF/PET. Time to clinical diagnosis varies between countries and pathways, from 14 weeks in primary care to 29 weeks for patients referred to a specialist.The Advisory Board considered a minimally‐invasive, patient‐friendly BBBM with high negative predictive value (NPV &gt; 90%) and moderate positive predictive value for Ab positivity could act as triage, excluding patients not needing confirmatory testing, while freeing capacity and allowing timely intervention for all others. The BBBM test would be useful in primary and secondary care, although payer coverage in primary care may limit its immediate use. In secondary care, the BBBM test could reduce unnecessary/invasive amyloid testing, and streamline the diagnostic pathway.ConclusionAn easy‐to‐use, minimally invasive BBBM test that detects amyloid pathology could be used with other tests/assessments to guide further diagnostic procedures or onward referral, reducing time to diagnosis and allowing timely access to potential DMTs. BBBMs have potential to be a first biomarker test, providing early‐stage information on underlying pathophysiology.

External validation of a clinical prediction model in multiple sclerosis

Background: Timely initiation of disease modifying therapy is crucial for managing multiple sclerosis (MS). Objective: We aimed to validate a previously published predictive model of individual treatment response using a non-overlapping cohort from the Middle East. Methods: We interrogated the MSBase registry for patients who were not included in the initial model development. These patients had relapsing MS or clinically isolated syndrome, a recorded date of disease onset, disability and dates of disease modifying therapy, with sufficient follow-up pre- and post-baseline. Baseline was the visit at which a new disease modifying therapy was initiated, and which served as the start of the predicted period. The original models were used to translate clinical information into three principal components and to predict probability of relapses, disability worsening or improvement, conversion to secondary progressive MS and treatment discontinuation as well as changes in the area under disability-time curve (ΔAUC). Prediction accuracy was assessed using the criteria published previously. Results: The models performed well for predicting the risk of disability worsening and improvement (accuracy: 81%–96%) and performed moderately well for predicting the risk of relapses (accuracy: 73%–91%). The predictions for ΔAUC and risk of treatment discontinuation were suboptimal (accuracy < 44%). Accuracy for predicting the risk of conversion to secondary progressive MS ranged from 50% to 98%. Conclusion: The previously published models are generalisable to patients with a broad range of baseline characteristics in different geographic regions.