Use Of Disease-modifying Treatments 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.

Delays in Multiple Sclerosis diagnosis (DIMES): protocol for a multicentre, observational study of multiple sclerosis diagnostic pathways in the United Kingdom and Republic of Ireland

BackgroundMultiple sclerosis (MS) is a leading cause of non-traumatic disability in young adults. Accumulating evidence indicates early diagnosis and early treatment improves long-term outcomes. However, the MS diagnostic pathway is increasingly complex, and delays may occur at several stages. Factors causing delays remain understudied. We aim to quantify the time taken for MS to be diagnosed, and characterise the diagnostic pathway and initial care provided, in the United Kingdom (UK) and Republic of Ireland (ROI).MethodsDelays In MultiplE Sclerosis diagnosis (DIMES) in the UK and ROI is a multicentre, observational, retrospective study that will be conducted via the Neurology and Neurosurgery Interest Group (NANSIG) collaborative network. Any hospital in the UK and ROI providing an MS diagnostic service is eligible to participate. Data on consecutive individuals newly diagnosed with MS between 1st July 2022 and 31st December 2022 will be collected. The primary outcomes are 1) time from symptoms/signs prompting referral to neurology, to MS diagnosis; and 2) time from referral to neurology for suspected MS, to MS diagnosis. Secondary outcomes include: MS symptoms, referring specialties, investigations performed, neurology appointments, functional status, use of disease modifying treatments, and support at diagnosis including physical activity, and follow up. Demographic characteristics of people newly diagnosed with MS will be summarised, adherence to quality standards summarised as percentages, and time-to-event variables presented with survival curves. Multivariable models will be used to investigate the association of demographic and clinical factors with time to MS diagnosis, as defined in our primary outcomes.DiscussionDIMES aims to be the largest multicentre study of the MS diagnostic pathway in the UK and ROI. The proposed data collection provides insights that cannot be provided from contemporary registries, and the findings will inform approaches to MS services nationally in the future.

What is the importance of family planning in multiple sclerosis? A study in the Brazilian population

IntroductionMultiple Sclerosis is a disease of young females at a reproductive age. Objectivediscuss family planning in the context of providing care for women with MS. Methodpatients with Multiple Sclerosis, female, aged between 18 and 45 years, from 01/Nov/2021 to 16/Jan/2022 participated, all of whom answered a questionnaire made available on the Google forms platform. ResultsA total of 233 responses were validated. Most patients discuss family planning during their medical care (61.4 %), use low-efficacy contraceptive methods (68.7 %) and do not plan to become pregnant (70.1 %). There is a high rate of use of disease-modifying treatments (88.9 %). Among those who had already become pregnant, most of them became pregnant before diagnosis and were statically younger than patients who became pregnant after diagnosis. ConclusionFamily planning should be discussed early on and be actively initiated by the health care professional assisting the patient and incorporated into the routine consultation. We suggest efforts should be put into ensuring a decrease in the rate of unplanned pregnancy in this population. Also, it is crucial to guarantee effective contraception in patients who express the wish not to become pregnant and are using disease-modifying treatments.

The Response Study: A French registry on pregnancy in women with MS and related disorders and their children up to 6 years-Protocol, recruitment status, and baseline characteristics.

Counseling on pregnancy is still challenging, particularly regarding the use of disease-modifying treatments (DMTs). We are lacking long-term outcomes in children exposed to DMTs. This study aimed to set up a French pregnancy registry for women with multiple sclerosis (MS) and related disorders nested within the Observatoire Français de la Sclérose en Plaques (OFSEP) cohort. Prospective, observational, multicentric, epidemiological study in France. Neurological visits are organized according to routine practice. Data are collected on the OFSEP minimal datasheet. Auto-questionnaires on pregnancy are completed by patients at Months 5-6 and 8 during pregnancy, and Months 3, 6, and 12 postpartum. A specific survey on analgesia is completed by anesthesiologists. Pediatric data are collected from the child's health book, where visits on Day 8, Month 9, and 24 are mandatory. Parents complete neurodevelopmental questionnaires at Year 1, Years 2 and 6. The RESPONSE study started in August 2019. On 7 April 2023, 515 women were included. Baseline demographics are presented. RESPONSE will provide rich information on the global management of pregnancy in France and prospective data on children until the age of 6 years, exposed or not to a DMT, including data on neurodevelopment that can be compared to the general population. EDMUS and ARSEP Foundation, Biogen, Roche.

"No association between disease modifying treatment and fatigue in multiple sclerosis".

Fatigue affects 60-90% of people with multiple sclerosis (MS). It reduces quality of life and the ability to work. The cause of fatigue in MS remains unknown. Several disease-modifying treatments (DMTs) slow the disease process in relapsing MS by suppressing neuroinflammation. We aimed to investigate if treatment with a DMT is associated with lower rates of fatigue. In this cross-sectional study of the MS population in three counties in Norway, we used the Fatigue Scale for Motor and Cognitive Functions (FSMC) and the Hospital Anxiety and Depression Scale (HADS) to assess patient-reported fatigue, anxiety and depression. Clinical data were retrieved from the electronic patient record system. We categorized DMTs as high-efficacy therapy or moderate-efficacy therapy. High-efficacy drugs included fingolimod, natalizumab, ocrelizumab, rituximab, alemtuzumab, daclizumab, and autologous hematopoietic stem cell transplantation. Moderate-efficacy drugs included interferons, glatiramer acetate, dimethyl fumarate, and teriflunomide. We included persons with relapsing MS only. Of 1142 patients, 80% had fatigue. Fifty-six percent of the patients were on DMTs (25% on moderate-efficacy treatment and 30% on high-efficacy treatment), 18% had discontinued treatment and 26% had never received any DMT. Sex, level of disability as measured by the Multiple Sclerosis Severity Score, anxiety and depression were independently associated with fatigue. Moderate-efficacy treatment was associated with less fatigue, but not after adjustment for other variables. There was no association between high-efficacy treatment and fatigue. We found no independent relationship between the use of disease-modifying treatment and fatigue in MS.

Patients with multiple sclerosis: COVID-19 related disease activity and hospitalisations based on a nationwide cohort study.

It has not previously been clarified if COVID-19 triggers disease activity and increases the risk of hospitalisation with COVID-19 in patients with multiple sclerosis. We examined the association between COVID-19 and the use of systemic corticosteroids prescriptions and hospital contacts at neurological departments as proxies of disease activity among patients with multiple sclerosis. Furthermore, we examined whether patients with multiple sclerosis were more likely to be hospitalised with COVID-19 compared to references. This study was based on nationwide health registries with data on the Danish population of 2,222,946 individuals with a positive COVID-19 PCR test. To study disease activity our study population consisted of all patients with multiple sclerosis and a positive COVID-19 PCR test. Our proxies for disease activity were compared after versus before a positive COVID-19 PCR test using a binomial regression model. Adjustments were made for age, sex, comorbidity, length of multiple sclerosis diagnosis, calendar period, vaccination, and immunomodulatory treatment. To study the risk of hospitalisation with COVID-19 in patients with multiple sclerosis our study population here consisted of all Danish citizens with a COVID-19 positive PCR test. In logistic regression models we estimated odds ratio (OR) for hospitalisation with COVID-19 in patients with multiple sclerosis relative to patients affected with other autoimmune diseases (inflammatory bowel disease/rheumatoid arthritis), and relative to individuals from the general population. Adjustments were made for age, sex, comorbidity, vaccination, and calendar period. To examine the impact of disease-modifying treatment, the risk of hospitalisation with COVID-19 was estimated in those with disease-modifying treatment versus those without any disease-modifying treatment. We included 7358 patients with multiple sclerosis and a positive COVID-19 PCR test. The adjusted incidence rate ratio (aIRR) for having corticosteroid prescriptions after COVID-19 in patients with multiple sclerosis was 0.93 (95% CI 0.78 - 1.10), and the aIRR for hospital contacts at neurological departments/admissions with multiple sclerosis as primary diagnosis after COVID-19 infection was 1.10 (95% 1.00-1.22). Adjusted OR (aOR) for hospitalisation with COVID-19 in the 30 days after a positive COVID-19 PCR test was 3.21 (95% CI 2.75-3.74) compared to patients with other autoimmune diseases and the aOR was 5.34 (95% CI 4.65-6.14) for patients with multiple sclerosis compared to all other individuals in the general population with a positive test. We found no increased risk of hospitalisations with COVID-19 in patients with multiple sclerosis using disease-modifying treatment 6 months prior to a positive COVID-19 PCR test compared to patients with multiple sclerosis without disease-modifying treatment (aOR 0.94 (95% CI 0.69-1.27)). In this nationwide cohort of patients with multiple sclerosis, COVID-19 did not seem to trigger multiple sclerosis disease activity (based on proxy variables). We found a significantly increased risk of being hospitalised with COVID-19 in the first 30 days after a positive COVID-19 PCR test in patients with multiple sclerosis irrespective of the type of reference population. In patients with multiple sclerosis, the use of disease-modifying treatment did not increase the risk of hospitalisation with COVID-19.

A Systematic Review of Clinical Practice Guidelines for Alzheimer's Disease and Strategies for Future Advancements.

Alzheimer's disease (AD) is a disease continuum from pathophysiologic, biomarker and clinical perspectives. With the advent of advanced technologies, diagnosing and managing patients is evolving. A systematic literature review (SLR) of practice guidelines for mild cognitive impairment (MCI) and AD dementia was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). This systematic literature review (SLR) aimed to summarize current clinical practice guidelines for screening, testing, diagnosis, treatment and monitoring in the AD continuum. The results of this SLR were used to propose a way forward for practice guidelines given the possible introduction of biomarker-guided technology using blood- or plasma-based assays and disease-modifying treatments (DMTs) targeted for early disease. 53 clinical practice guidelines were identified, 15 of which were published since 2018. Screening for asymptomatic populations was not recommended. Biomarker testing was not included in routine diagnostic practice. There was no consensus on which neurocognitive tests to use to diagnose and monitor MCI or AD dementia. Pharmacologic therapies were not recommended for MCI, while cholinesterase inhibitors and memantine were recommended for AD treatment. The pre-2018 and post-2018 practice guidelines share similar recommendations for screening, diagnosis and treatment. However, once DMTs are approved, clinicians will require guidance on the appropriate use of DMTs in a clinical setting. This guidance should include strategies for identifying eligible patients and evaluating the DMT benefit-to-risk profile to facilitate shared decision-making among physicians, patients and care partners. Regular evidence-based updates of existing guidelines for the AD continuum are required over the coming decades to integrate rapidly evolving technologic and medical scientific advances and bring emerging approaches for management of early disease into clinical practice. This will pave the way toward biomarker-guided identification and targeted treatment and the realization of precision medicine for AD.

Kappa free light chain and neurofilament light independently predict early multiple sclerosis disease activity—a cohort study

Inter-individual courses of multiple sclerosis (MS) are extremely variable. The objective of this study was to investigate whether κ-free light chain (κ-FLC) index and serum neurofilament light (sNfL) have an additive predictive value for MS disease activity. Patients with early MS who had cerebrospinal fluid (CSF) and serum sampling at disease onset were followed for four years. At baseline, age, sex, disease duration, number of T2-hyperintense (T2L), and contrast-enhancing T1 lesions (CEL) on MRI were determined. During follow-up, the occurrence of a second clinical attack and start of disease-modifying treatment (DMT) were registered. κ-FLC was measured by nephelometry, and κ-FLC index calculated as [CSF κ-FLC/serum κ-FLC]/albumin quotient. sNfL was determined by single-molecule array, and age- and body-mass-index adjusted Z scores were calculated. A total of 86 patients at a mean age of 33±10 years and with a female predominance of 67% were included; 36 (42%) patients experienced a second clinical attack during follow-up. Cox regression analysis adjusted for age, sex, T2L, CEL, disease and follow-up duration, and DMT use during follow-up revealed that both κ-FLC index as well as sNfL Z score independently predict time to second clinical attack. The chance for freedom of relapse within 12 months was 2% in patients with high levels of κ-FLC index (>100) and high sNfL Z score (>3), 30% in patients with high κ-FLC index (>100) and lower sNfL Z score (≤3), 70% in patients with lower κ-FLC index (≤100) but high sNfL Z score (>3), and 90% in patients with lower levels of κ-FLC index (≤100) and sNfL Z score (≤3). κ-FLC index and sNfL Z score have an additive predictive value for early MS disease activity that is independent of known predictors. This study was funded by a grant of the charitable foundation of the Austrian Multiple Sclerosis Society.

Sexual dysfunction in female and male people with multiple sclerosis: disability, depression and hormonal status matter.

Sexual dysfunction (SD) in people with multiple sclerosis (pwMS) is common and an often underestimated issue in the care of pwMS. The objective of the study was to evaluate risk factors for SD in pwMS, correlate its prevalence with patient-reported measures (quality of life and physical activity) and analyse its association with hormonal status. Sexual dysfunction was determined in 152 pwMS using the Multiple Sclerosis Intimacy and Sexuality Questionnaire 19. A logistical regression model was used to identify independent risk factors for SD. The prevalence of SD in pwMS was 47%. Independent risk factors for the development of SD were ever-smoking (odds ratio [OR] 3.4, p=0.023), disability as measured by the Expanded Disability Status Scale (OR 2.0, p < 0.001), depression (OR 4.3, p=0.047) and bladder and bowel dysfunction (OR 8.8, p < 0.001); the use of disease-modifying treatment was associated with a lower risk for SD (OR 0.32, p=0.043). SD was associated with worse quality of life (Multiple Sclerosis Impact Scale 29: physical score 6.3 vs. 40.0; psychological score 8.3 vs. 33.3; both p < 0.001) and lower physical activity (Baecke questionnaire, p < 0.001). Laboratory analysis revealed significantly higher luteinizing hormone and follicle-stimulating hormone levels and lower 17-beta oestradiol, androstenedione, dehydroepiandrosterone sulfate, oestrone and anti-Mullerian hormone levels in female pwMS with SD. In male pwMS and SD, there was a significant decrease in inhibin B levels. Our findings highlight the requirement of a holistic approach to SD in MS including physical, neurourological and psychosocial factors. Active screening for SD, especially in patients with disability, depression or bladder and bowel dysfunction, is recommended.

The impact of healthcare systems on the clinical diagnosis and disease-modifying treatment usage in relapse-onset multiple sclerosis: a real-world perspective in five registries across Europe.

Prescribing guidance for disease-modifying treatment (DMT) in multiple sclerosis (MS) is centred on a clinical diagnosis of relapsing-remitting MS (RRMS). DMT prescription guidelines and monitoring vary across countries. Standardising the approach to diagnosis of disease course, for example, assigning RRMS or secondary progressive MS (SPMS) diagnoses, allows examination of the impact of health system characteristics on the stated clinical diagnosis and treatment access. We analysed registry data from six cohorts in five countries (Czech Republic, Denmark, Germany, Sweden and United Kingdom) on patients with an initial diagnosis of RRMS. We standardised our approach utilising a pre-existing algorithm (DecisionTree, DT) to determine patient diagnoses of RRMS or secondary progressive MS (SPMS). We identified five global drivers of DMT prescribing: Provision, Availability, Funding, Monitoring and Audit, data were analysed against these concepts using meta-analysis and univariate meta-regression. In 64,235 patients, we found variations in DMT use between countries, with higher usage in RRMS and lower usage in SPMS, with correspondingly lower usage in the UK compared to other registers. Factors such as female gender (p = 0.041), increasing disability via Expanded Disability Status Scale (EDSS) score (p = 0.004), and the presence of monitoring (p = 0.029) in SPMS influenced the likelihood of receiving DMTs. Standardising the diagnosis revealed differences in reclassification rates from clinical RRMS to DT-SPMS, with Sweden having the lowest rate Sweden (Sweden 0.009, range: Denmark 0.103 - UK portal 0.311). Those with higher EDSS at index (p < 0.03) and female gender (p < 0.049) were more likely to be reclassified from RRMS to DT-SPMS. The study also explored the impact of diagnosis on DMT usage in clinical SPMS, finding that the prescribing environment and auditing practices affected access to treatment. This highlights the importance of a healthcare system's approach to verifying the clinical label of MS course in facilitating appropriate prescribing, with some flexibility allowed in uncertain cases to ensure continued access to treatment.

Therapeutic Response in Pediatric Neuromyelitis Optica Spectrum Disorder.

Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune condition, which can lead to significant disability, and up to 3%-5% of the cases have a pediatric onset. There are limited studies to guide physicians in disease-modifying treatment (DMT) choices for children with NMOSD. This retrospective cohort study evaluated children with NMOSD cases followed at 12 clinics in the US Network of Pediatric MS Centers. Cases were classified as aquaporin-4 antibody positive (AQP4+) and double seronegative (DS) when negative for AQP4+ and for myelin oligodendrocyte glycoprotein (MOG) antibody. The effect of initial DMTs including rituximab, mycophenolate, azathioprine, and IV immunoglobulin (IVIg) on the annualized relapse rate (ARR) was assessed by negative binomial regression. Time to disability progression (EDSS score increase ≥1.0 point) was modeled with a Cox proportional-hazards model. A total of 91 children with NMOSD were identified: 77 AQP4+ and 14 DS (85.7% females; 43.2% White and 46.6% African American). Eighty-one patients were started on a DMT, and 10 were treatment naive at the time of the analysis. The ARR calculated in all serogroups was 0.25 (95% CI 0.13-0.49) for rituximab, 0.33 (95% CI 0.19-0.58) for mycophenolate, 0.40 (95% CI 0.13-1.24) for azathioprine, and 0.54 (95% CI 0.28-1.04) for IVIg. The ARR in the AQP4+ subgroup was 0.28 (95% CI 0.14-0.55) for rituximab, 0.39 (95% CI 0.21-0.70) for mycophenolate, 0.41 (95% CI 0.13-1.29) for azathioprine, and 0.54 (95% CI 0.23-1.26) for IVIg. The ARR in the treatment-naive group was 0.97 (95% CI 0.58-1.60) in all serogroups and 0.91 (95% CI 0.53-1.56) in the AQP4+ subgroup. None of the initial DMT had a statistically significant effect on EDSS progression. The use of DMTs, particularly rituximab, is associated with a lowered annualized relapse rate in children with NMOSD AQP4+. This study provides Class IV evidence that use of disease-modifying treatments is associated with a lowered annualized relapse rate in children with NMOSD AQP4+.

Trends of Disease Modifying Treatment Use in Sickle Cell Disease: Retrospective Analysis of Claims Data, 2014-2020

Introduction Over the last few years, several disease modifying treatments (DMTs) have received approval for the treatment of sickle cell disease (SCD). DMTs target key aspects of the pathophysiological processes of SCD and can reduce disease progression and morbidity. Prior to 2017, hydroxyurea was the only FDA-approved pharmacological DMT. After decades of limited pharmacologic options, three novel therapeutics have become available: L-glutamine, voxelotor, and crizanlizumab-tmca. However, data on real-world use of contemporary DMTs are limited to single centers, small sample sizes, and usually focus on single DMTs. Investigating the uptake of new DMTs in SCD is important as patients with SCD continue to experience high morbidity and mortality and, therefore, aggressive adoption of new treatments is paramount to improve patient outcomes. This study uses claims data from a large national insurer to provide information on treatment patterns for all four DMTs from 2014-2020. Methods We conducted a retrospective cohort study using de-identified prescription and medical claims data from the Optum's Clinformatics Data Mart Database (Eden Prairie, MN) from January 2014 - September 2020. Optum contains information on commercial and Medicare insurance beneficiaries. We identified SCD individuals as those with a qualifying ICD-9/10 diagnosis code for SCD in the inpatient or outpatient setting within the study timeframe (index date).We required 6 months of continuous enrollment prior to the index date to collect patient characteristics. Outcomes evaluated were rates of DMT use per year for all DMTs and by each individual DMT. Rates of DMT use were calculated as the number of SCD individuals with at least one prescription fill for the respective DMT divided by total number of SCD individuals in the given year. We also evaluated sociodemographic and clinical characteristics . Results A total of 5,688 individuals had a diagnosis of SCD between 2014-2020. In our cohort, 21.8% of individuals were less than 18 years of age, while 43.1% were between 18-45 years old. During the study period, we identified 1,933 individuals who had at least one prescription fill for any DMT and 3,755 individuals who had no fill for any DMT. Descriptive analyses of patient characteristics revealed that compared to non-DMT users, DMT users were more likely to be male (45.9% vs 40.5%), to be aged 18-45 (50.1% vs 39.5% ), have a higher number of pain episodes (4.1 vs 2.3), and a greater number of SCD complications such as acute chest syndrome (9.1% vs. 3.3%) and avascular necrosis (9.7% vs. 3.0%). For healthcare utilization, DMT users were more likely to have emergency department (ED) visits and inpatient hospitalizations compared to non-DMT users (7.0% vs. 3.7%; 12.1% vs. 8.1% respectively). However, non-DMT users were more likely to have outpatient visits (13.4% vs. 12.5%). When evaluating trends in treatment use, the overall use of DMTs has remained stable with a modest increase over the last 6 years. Analysis of individual DMT use patterns revealed that hydroxyurea use followed the same pattern. Newer DMTs were used in less than 5% of the population with a slight increase in rate of use over the years after approval. Conclusion DMT users had a higher prevalence of SCD complications, pain crises, inpatient hospitalizations and ED visits, which likely reflects indication bias, and were more likely to be young adults, possibly because of concerns over poorer tolerability in older patients. Overall, in spite of the availability of newer DMTs since 2017, the overall rate of DMT use has remained largely stable with only modest increases. As expected, the most commonly used DMT was hydroxyurea, however, <30% of SCD individuals used hydroxyurea over the last 6 years, which confirms prior data showing that hydroxyurea is under prescribed and underutilized in SCD. Lack of guidelines with respect to the newer DMTs may have hampered more widespread adoption of these drugs, alongside knowledge gaps regarding their mechanism of action and place in therapy. In addition, the high cost of the new DMTs and lack of payer approval may have also been a factor in their poor uptake. These data point to the importance of educating health care providers and patients about the importance of pharmacologic DMTs in SCD, and of addressing all potential barriers to their utilization. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

RWD105 Healthcare Resource Utilization and Disease Modifying Treatment Use Among Patients with Multiple Sclerosis in Sweden: A Nationwide Register-Based Study

RWD105 Healthcare Resource Utilization and Disease Modifying Treatment Use Among Patients with Multiple Sclerosis in Sweden: A Nationwide Register-Based Study

P.027 Multiple Sclerosis Self-reflective Treatment Evaluation Program (MS-STEP): alignment of current practices to the 2020 Canadian MS Working Group recommendations

Background: New Canadian treatment optimization recommendations (TOR) were released in 2020 to guide clinicians on the optimal use of disease modifying treatments (DMTs). The alignment of current practices to TOR was investigated to identify potential areas for improvement in patient care. Methods: From January–July 2021, a chart audit of 160 patients was conducted by a sample of Canadian neurologists. Patient selection criteria included adult patients with relapsing-remitting MS, who had been switched from an initial DMT. Results: In alignment with TOR, most patients received a platform therapy initially (89%; n=143) and suboptimal efficacy response (MRI changes, relapses, disability progression) was the most common trigger for switching treatment. Furthermore, the expanded disability status scale was used in 94% (n=151) of cases during clinical assessment. In some instances, neurologists did not adhere to TOR. Only 10% (n=16) of patients were tested for cognitive function and over half (58%; n=93) did not receive gadolinium contrast at re-baseline MRI. Major criteria for switching therapies based on relapse rate, severity/recovery, or MRI were not followed in (n=4; n=27; n=7) patients respectively. Conclusions: Canadian neurologists are generally aligned with recent TOR for MS. However, they are not switching nearly as often or as early as per TOR criteria.

The risk of infections for multiple sclerosis and neuromyelitis optica spectrum disorder disease-modifying treatments: Eighth European Committee for Treatment and Research in Multiple Sclerosis Focused Workshop Review. April 2021

Over the recent years, the treatment of multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) has evolved very rapidly and a large number of disease-modifying treatments (DMTs) are now available. However, most DMTs are associated with adverse events, the most frequent of which being infections. Consideration of all DMT-associated risks facilitates development of risk mitigation strategies. An international focused workshop with expert-led discussions was sponsored by the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) and was held in April 2021 to review our current knowledge about the risk of infections associated with the use of DMTs for people with MS and NMOSD and corresponding risk mitigation strategies. The workshop addressed DMT-associated infections in specific populations, such as children and pregnant women with MS, or people with MS who have other comorbidities or live in regions with an exceptionally high infection burden. Finally, we reviewed the topic of DMT-associated infectious risks in the context of the current SARS-CoV-2 pandemic. Herein, we summarize available evidence and identify gaps in knowledge which justify further research.

Updated Perspectives on the Challenges of Managing Multiple Sclerosis During Pregnancy

Multiple sclerosis (MS) is a chronic immune-mediated, inflammatory, and degenerative disease that is up to three times more frequent in young women. MS does not alter fertility and has no impact on fetal development, the course of pregnancy, or childbirth. The Pregnancy in Multiple Sclerosis Study in 1998 showed that pregnancy, mostly in untreated women, did not adversely affect MS, as disease activity decreased during pregnancy (although it significantly increased in the first trimester postpartum). These findings, together with the limited information available on the potential risks of fetal exposure to disease modifying treatments (DMTs), meant that women were advised to delay the onset of DMTs, stop them prior to conception, or, in case of unplanned pregnancy, discontinue them when pregnancy was confirmed. Now, many women with MS receive DMTs before pregnancy and, despite being considered a period of MS stability, up to 30% of patients could relapse in the first trimester postpartum. Factors associated with an increased risk of relapse and disability during pregnancy and postpartum include relapses before and during pregnancy, a greater disability at the time of conception, the occurrence of relapses after DMT cessation before conception, and the use of high-efficacy DMTs before conception, especially natalizumab or fingolimod. Strategies to prevent postpartum activity are needed in some patients, but consensus is lacking regarding the therapeutic strategies for women with MS of a fertile age. This, along with the increasing number of DMTs, means that the decision-making processes in aspects related to family planning and therapeutic strategies before, during, and after pregnancy are increasingly more complex. The purpose of this review is to provide an update on pregnancy-related issues in women with MS, including recommendations for counseling, general management, use of DMTs in pre-pregnancy, pregnancy, and postpartum periods, and breastfeeding-related aspects of DMTs.

Treatment of multiple sclerosis during COVID-19 pandemic

Multiple sclerosis patients are by definition more susceptible to infections, which dependents on the use of disease-modifying treatments. Depending on the mechanism of action, individual disease-modifying treatments carry different risks. As a result, patients require an individualised approach to initiating and continuing new treatments. This problem became very important during the COVID-19 pandemic. In the case of drugs with different mechanisms of action on the immune system, the impact of therapy on susceptibility to SARS-CoV-2 infections and the course of COVID-19 should be considered. Based on the risk/ benefit analysis for the patient, individual therapies have been assigned recommendations: 1) low-risk therapies (glatiramer acetate, interferons, dimethyl fumarate, teriflunomide) – discontinuation of therapy and delay of treatment initiation is not recommended; 2) moderate-risk therapies (fingolimod, natalizumab, ocrelizumab, cladribine) – require caution, individual risk/benefit assessment, risk analysis of multiple sclerosis symptom exacerbation after drug discontinuation; 3) high-risk therapies (alemtuzumab, mitoxantrone, haematopoietic stem cells transplantation) – treatment initiation is not recommended, administration of subsequent doses requires extreme caution. The article reviews the recommendations and publications from the last 2 years, taking into account the changing views on the treatment of multiple sclerosis in the time of COVID-19 pandemic.

Primary myelofibrosis in untreated sickle cell disease: Are adult patients at higher risk for developing hematological myeloid neoplasms?

Primary myelofibrosis in untreated sickle cell disease: Are adult patients at higher risk for developing hematological myeloid neoplasms?

Clinical effects associated with five-year retinal nerve fiber layer thinning in multiple sclerosis

BackgroundNeurodegenerative changes in multiple sclerosis (MS) are associated with long-term disability progression (DP). Optical coherence tomography (OCT) measures may be used to monitor DP. ObjectiveTo determine significant effects driving the changes in OCT-based peripapillary retinal nerve fiber layer (pRNFL) in heterogeneous group of MS patients. MethodsTotal of 144 MS patients (109 relapsing-remitting MS and 35 progressive MS (PMS) with mean age at baseline of 47.6 and 56.5 years old, respectively) underwent clinical and OCT examination over 5-year follow-up. All OCT exams were reviewed using the OSCAR-IB criteria. The 5-year DP was determined based on Expanded Disability Status Scale (EDSS) changes and MS clinical trial criteria. Data regarding previous history of MS optic neuritis (MSON) and use of disease modifying treatment (DMT) was derived by in-person interview and review of electronic medical records. Mixed model-type of repeated measure analysis determined effects driving pRNFL change for analysis which utilized all eyes separately. ResultsOver an average of 5.3-years follow-up, the MS population demonstrated significant pRNFL thinning (F = 16.108, p < 0.001). The pRNFL thinning was greater due to progressive MS subtype (F = 5.102, p = 0.025), greater age at baseline (F = 4.554, p = 0.034), occurrence of DP (F = 6.583, p = 0.011), and previous history of MSON (F = 7.053, p = 0.008). Use of any or highly potent DMT (natalizumab versus first-line injectable treatments versus no DMT) significantly reduced the pRNFL thinning (F = 8.367, p = 0.004) over the follow-up. Lastly, occurrence of DP in PMS patients older than 50 years old was associated with greater pRNFL thinning (F = 6.667, p = 0.013). ConclusionLongitudinal pRNFL changes are modified by age, disease subtype, disabiltiy progression, history of MSON, DMT use and their interactions.

Maternal education has significant influence on progression in multiple sclerosis

ObjectiveThe identification of potential risk factors for disease severity is of great importance in the treatment of multiple sclerosis. The influence of socioeconomic status on progression in multiple sclerosis (MS) is sparsely investigated. Our aim was to investigate how socioeconomic status in adolescence influences disease progression in later life. MethodsA total of 1598 patients with multiple sclerosis from a well-defined population in Norway were included. Detailed information on disease progression, measured by expanded disability status scale (EDSS) and multiple sclerosis severity score (MSSS), were combined with data on socioeconomic factors. We used residency and parental level of education at patients’ age 16 and exposure to second-hand smoking as a measure of socioeconomic status in adolescence, adjusting for the same variables as well as use of disease modifying treatments at prevalence date 01.01.18. ResultsHigh maternal level of education at patients’ age 16 was significantly associated with less pronounced disease progression measured by MSSS (β-coefficient -0.58, p = 0.015), younger age and lower EDSS at disease onset, and shorter time from onset to diagnosis. No significant associations were found for paternal education level and MSSS. The use of any disease modifying treatment before prevalence date was significantly associated with disease progression (β-coefficient -0.49, p=0.004), while residence, current and second-hand smoking were not. ConclusionThis study on a population-based, real-world cohort shows that the parental level of education has a significant impact on a timely diagnosis of MS. In addition to disease modifying treatment, maternal level of education also had an impact on disease progression in later life.