Use Of Disease-modifying Drugs Research Articles

P0356 A case of pulmonary nodules in Ulcerative Colitis and primary sclerosing cholangitis: is it drug or disease?

Abstract Background Pulmonary manifestation of inflammatory bowel disease (IBD) is rare, with a broad range of lung diseases including airways, parenchymal, pleural, and pulmonary vascular disease. It is commonly associated with concurrent use of disease-modifying drugs. We present a case of a 26 year old man with ulcerative colitis and primary sclerosing cholangitis (PSC) who developed lung nodules. Methods Case summary: He was diagnosed with PSC in 2017 and ulcerative colitis in 2018. He had active colitis while on an escalated dose of adalimumab, therefore he was switched to vedolizumab. His faecal calprotectin improved but due to ongoing rectal bleeding, the dose of vedolizumab was escalated from 8 to 4 weekly. 5 months after starting vedolizumab he developed night sweats, dry cough, and breathlessness. He has no history of foreign travel, exposure to tuberculosis, industrial exposure, or bird keeping. Results His initial investigations showed a raised CRP and bilirubin. His CT chest showed numerous lung nodules in both lower lobes. His sputum culture, AFB, and fungal blood markers were negative. Samples were also sent from a bronchoalveolar lavage fluid including for pneumocystis jirovecii, which were negative. He was treated with antimicrobials and antifungal, without improvement. He subsequently underwent a lung biopsy, which showed inflammatory changes in an interstitial pattern, which could be related to the biologic therapy, or underlying disease. Staining for fungus, EBV, CMV, HSV were negative. He was treated as bronchiolitis obliterans organising pneumonitis induced by vedolizumab. Vedolizumab was stopped and prednisolone 40mg was started. His symptoms and inflammatory markers improved, and subsequent pulmonary imaging showed a reduction in the size of the lung nodules. Tapering the prednisolone dose to 10mg unfortunately caused a progression in the lung nodules, despite cessation of vedolizumab, which makes it less likely as the culprit drug. Prednisolone was then increased back up to 40mg, resulting in almost complete resolution of the lung nodules, with the plan for a much slower tapering. Despite the high doses of steroid his colitis is still moderately active on colonoscopy. However, further advanced therapy had to be put on hold while waiting for his lung nodules to resolve. Conclusion It remains difficult to determine whether his pulmonary disease is secondary to the biologic drugs, or the underlying disease process of ulcerative colitis. While pulmonary disease associated with IBD has been widely reported, there is currently unclear understanding of its pathophysiology and treatment. Clinicians need to be aware of this rare entity in IBD in order to improve patient outcomes.

Methotrexate promotes the release of granulocyte–macrophage colony-stimulating factor from rheumatoid arthritis fibroblast-like synoviocytes via autocrine interleukin-1 signaling

BackgroundActivated fibroblast-like synoviocytes (FLS) are drivers of synovitis and structural joint damage in rheumatoid arthritis (RA). Despite the use of disease-modifying drugs, only about 50% of RA patients reach remission in real-world settings. We used an unbiased approach to investigate the effects of standard-of-care methotrexate (MTX) and a Janus kinase inhibitor, tofacitinib (TOFA), on gene expression in RA-FLS, in order to identify untargeted disease mediators.MethodsPrimary RA-FLS were activated by stimulation with interleukin-1β (IL-1β) or platelet-derived growth factor + IL-1β in the presence or absence of MTX or TOFA, with or without additional inhibitors. Co-cultures of synovial cells were performed in direct and indirect systems. Cells were collected for RNA sequencing or qPCR, and supernatants were analyzed for protein concentrations.ResultsSix thousand three hundred fifty genes were differentially expressed, the majority being upregulated, in MTX-treated activated RA-FLS and 970 genes, the majority being downregulated, in TOFA-treated samples. Pathway analysis showed that MTX had largest effects on ‘Molecular mechanisms of cancer’ and TOFA on ‘Interferon signaling’. Targeted analysis of disease-associated genes revealed that MTX increased the expression of cell cycle-regulating genes but also of pro-inflammatory mediators like IL-1α (IL1A) and granulocyte–macrophage colony-stimulating factor, GM-CSF (CSF2). The MTX-promoted expression of CSF2 in activated RA-FLS peaked at 48 h, could be mediated via either NF-κB or AP-1 transcription factors, and was abrogated by IL-1 inhibitors (IRAK4 inhibitor and anakinra). In a co-culture setting, MTX-treatment of activated RA-FLS induced IL1B expression in macrophages.ConclusionsMTX treatment induces secretion of IL-1 from activated RA-FLS which by autocrine signaling augments their release of GM-CSF. This unexpected effect of MTX might contribute to the persistence of synovitis.

Can we predict kidney involvement in patients with systemic lupus erythematosus? A retrospective cohort study with independent validation.

To discern predictive factors for incident kidney involvement in patients with systemic lupus erythematosus (SLE). Patients with SLE from the 'Attikon' Lupus cohort were monitored for lupus nephritis (LN), defined by kidney histology and/or classification criteria. Demographic and clinical characteristics at baseline were compared against patients who did not develop LN. LN-free survival curves were generated by Kaplan-Meier. A multivariate Cox proportional hazards model was used to identify independent predictors of LN. Independent validation was performed in the University of Crete Lupus registry. Among the 570 patients in the derivation cohort, 59 exhibited LN as their initial presentation, while an additional 66 developed LN during the follow-up period (collectively, 21.9% incidence). In the latter group, baseline factors predictive of subsequent kidney involvement were male sex (multivariable-adjusted [a]HR 4.31, 95% CI: 1.82-10.2), age of SLE diagnosis below 26 years (aHR 3.71, 95% CI: 1.84-7.48), high anti-dsDNA titre (aHR 2.48, 95% CI: 1.03-5.97) and low C3 and/or C4 (although not statistically significant, aHR 2.24, 95% CI: 0.83-6.05, p= 0.11). A combination of these factors at time of diagnosis conferred an almost 90-fold risk compared with serologically inactive, older, female patients (aHR 88.77, 95% CI : 18.75-420.41), signifying a very high-risk group. Independent validation in the Crete Lupus registry showed concordant results with the original cohort. Male sex, younger age and serologic activity at SLE diagnosis are strongly associated with subsequent kidney involvement. Vigilant surveillance and consideration of early use of disease-modifying drugs is warranted in these subsets of patients.

Vaccine adherence and adverse events of the SARS-COV vaccine in patients with inflammatory bowel disease

ObjectiveTo assess adherence to and the adverse effects of the SARS-COV vaccine in patients with inflammatory bowel disease (IBD). Patients and methodsThis is an observational, analytical, cross-sectional study. Sociodemographic and clinical data, SARS-COV vaccine data, medications for IBD with use during the vaccination period, and adverse events during the vaccination period were collected. Carried out logistic regressions with robust variance estimation to estimate the odds ratio with the respective 95% confidence intervals (95%CI) to assess the factors associated with non-serious adverse effects following vaccine doses as outcome variables. Results194 patients participated, with vaccine compliance of 78.3% for three doses of any vaccine (n=152). Local symptoms and mild systemic symptoms predominated, regardless of the type of vaccine. The first dose of the SARS-COV vaccine with AstraZeneca had a higher percentage of patients with vaccine symptoms. AstraZeneca vaccine increased the chance of non-serious adverse effects in IBD patients by 2.65 times (95% CI: 1.38–5.08; p=0.003), regardless of age, gender, physical activity, excess weight, use of disease-modifying drugs, immunobiological and corticosteroids. CoronaVac vaccine was associated with asymptomatic patients at the first dose and reduced the chance of adverse effects by 0.28 times (OR: 0.284; 95%CI: 0.13–0.62; p=0.002). ConclusionLocal symptoms and mild systemic symptoms predominated, regardless of the type of vaccine. Using CoronaVac in the first dose reduced the chances of adverse effects, while AstraZeneca increased the risk of adverse effects.

Multiple sclerosis disease-modifying drug use by immigrants: a real-world study

Little is known about disease-modifying drug (DMD) initiation by immigrants with multiple sclerosis (MS) in countries with universal health coverage. We assessed the association between immigration status and DMD use within 5-years after the first MS-related healthcare encounter. Using health administrative data, we identified MS cases in British Columbia (BC), Canada. The index date was the first MS-related healthcare encounter (MS/demyelinating disease-related diagnosis or DMD prescription filled), and ranged from 01/January/1996 to 31/December/2012. Those included were ≥ 18 years old, BC residents for ≥ 1-year pre- and ≥ 5-years post-index date. Persons becoming permanent residents 1985–2012 were defined as immigrants, all others were long-term residents. The association between immigration status and any DMD prescription filled within 5-years post-index date (with the latest study end date being 31/December/2017) was assessed using logistic regression, reported as adjusted odds ratios (aORs) with 95% confidence intervals (CIs). We identified 8762 MS cases (522 were immigrants). Among immigrants of lower SES, odds of filling any DMD prescription were reduced, whereas they did not differ between immigrants and long-term residents across SES quintiles (aOR 0.96; 95%CI 0.78–1.19). Overall use (odds) of a first DMD within 5 years after the first MS-related encounter was associated with immigration status.

Impact of Srs-CoV2 Infection on Pain Crises and Acute Chest Syndome in Patients with Sickle Cell Anemia: A Retrospective Multi-Cohort Study Based on USA Data from 2020-2022

Objective: To determine the impact of SARS-CoV-2 infection on vaso-occlusive pain crisis (VOC) and acute chest syndrome (ACS), incidence, and outcomes in sickle cell anemia (SCA) patients. Method: This retrospective study used the TriNetX USA health research network database to identify SCA patients (Hb-SS, Sβ0-thal) ages 1-50 with and without concomitant SARS-CoV-2 infection from May 2020 to May 2022. A total of 6 cohorts were created: pain crisis with/without SARS-CoV-2, ACS with/without SARS-CoV-2, and SARS-CoV-2 without pain crisis/ACS. Patients with SARS-CoV-2 and pain crisis/ACS were compared to 2 cohorts (SARS-CoV-2 without pain crisis/ACS) for demographic characteristics, baseline laboratory parameters, disease-modifying drug use, and influenza/COVID-19 vaccination status by t-tests. Pain crisis/ACS patients with SARS-CoV-2 were then compared to 2 cohorts (pain crisis/ACS without concomitant infection) for demographic characteristics, and relative risk for acute settings of care, pain control, laboratory parameters/outcomes (including hemolytic and inflammatory markers), procedures (blood transfusion) and mortality. Results : The incidence of pain crises and ACS in SCA patients following SARS-CoV-2 infection was 34 and 27 per 100 patients, respectively. The risk of developing ACS was significantly increased by SARS-CoV-2 infection (2.57% vs. 1.17%, RR 2.2), but not the risk of developing a pain crisis (RR 1.04). Pain crisis and ACS patients with concomitant SARS-CoV-2 infection had a greater risk for inpatient services, subsequent hospital visits, opioid and non-opioid analgesia, blood transfusions, and concerning hemolytic and inflammatory markers compared to those without the infection. Patients with SARS-CoV-2 who did not develop pain crises/ACS had higher baseline hemoglobin levels prior to infection compared to patients who developed pain crisis/ACS. There was a higher rate of COVID-19 and influenza vaccination in the cohorts who did not develop pain crisis/ACS and might have improved pain crisis rates (but not ACS) following SARS-CoV-2 infection. Conclusions: COVID-19 illness had an impact on the incidence of both pain crises and ACS, significantly increased the risk of developing ACS, and influenced morbidity outcomes for both pain crises and ACS. Prior vaccination against influenza and COVID-19 may represent a protective factor for developing pain crises.

Predictive value of retinal atrophy for cognitive decline across disease duration in multiple sclerosis

BackgroundWe investigated the association between changes in retinal thickness and cognition in people with MS (PwMS), exploring the predictive value of optical coherence tomography (OCT) markers of neuroaxonal damage for...

Quadruple therapy for heart failure before and after electronic cardiac device implantation - are we hitting our targets?

Abstract Background Quadruple therapy is currently recommended pharmacological treatment for heart failure with reduced ejection fraction (HFrEF). It consists of beta-blockers, mineralocorticoid receptor antagonists (MRA), angiotensin converting enzyme inhibitors (ACE-I) – recently suggested to be replaced with angiotensin receptor/neprilysin inhibitor (ARNI), and sodium-glucose cotransporter-2 inhibitors (SGLT2-I). Patients eligible for implantable cardioverter-defibrillator (ICD) or cardiac resynchronization therapy (CRT) implantation should have therapy titrated to evidence-based target doses prior to the procedure, whenever tolerable. Compliance with guidelines as well as distinction in prescription practice before and after device implantation in the era of quadruple HFrEF therapy has not yet been fully researched. Purpose The purpose of this study is to evaluate the use of disease-modifying drugs in corresponding target doses in patients with HFrEF eligible for ICD or CRT implantation, prior to and after the procedure. Methods This is a retrospective observational study which included patients with HFrEF hospitalized for ICD or CRT implantation in a single tertiary centre from January 2021 to January 2023. Data was collected through patients' medical history and phone calls. Results We collected data on a total of 107 patients with HFrEF and ICD or CRT implantation. Most patients received all four classes of guideline-directed therapy before ICD or CRT implantation: beta-blockers (91,6%), MRA (86,0%), ACE-I (31,8%) or ARNI (59,8%) and SGLT2-I (59,8%). Evidence-based target doses were reached for 10,2%, 52,2%, 11,8%, 32,8% and 100% patients receiving beta-blockers, MRA, ACE-I, ARNI and SGLT2i respectively. After hospitalization for device implantation, results pointed to an increase in prescription of beta-blockers (99,1%), MRA (97,2%), and most notably SGLT2-I (87,9%), while more ACE-I (19,6%) were replaced with ARNI (75,7%). Target doses were reached for 19,8%, 72,1%, 28,6%, 37,0%, and 100% patients receiving beta-blockers, MRA, ACE-I, ARNI, and SGLT2-I respectively. Conclusions Most of the examined patients have been receiving all four drug classes prior to device implantation. We noticed a rising trend in recruiting novel heart failure drugs, ARNI and SGLT2-I, after the procedure. However, drug titration was non-compliant with guidelines. There was a slight improvement in up-titration of therapy after the procedure, which could be explained by more common medication adjustments by electrophysiologists during device control sessions as well as better drug tolerability after device implantation. Regardless, a minority of patients received ACE-I, ARNI and beta blockers in target doses. Despite several objective obstacles to adequate administration of disease-modifying drugs, including intolerability and patients’ non-adherence, further effort in up-titrating guideline-directed medical therapy should be applied.Therapy administration practice

64 The Biomarker-Based Etiological Diagnosis of Neurocognitive Disorders: the European Inter-Societal Delphi Consensus

Objective:In the field of neurocognitive disorders, the perspective offered by new disease-modifying therapy increases the importance of etiological diagnosis. The prescription of cerebrospinal fluid analysis (CSF) and imaging biomarkers is a common practice in the clinic but is often driven more by personal expertise and local availability of diagnostic tools than by evidence of efficacy and cost-effectiveness analysis. This leads to a widely heterogeneous dementia care across Europe. Therefore, a European initiative is currently being conducted to establish a consensus for biomarker-based diagnosis of patients with mild cognitive impairment (MCI) and mild dementia.Participants and Methods:Since November 2020, a European multidisciplinary task force of 22 experts from 11 scientific societies have been defining a diagnostic workflow for the efficient use of biomarkers. The Delphi consensus procedure was used to bridge the gaps of incomplete scientific evidence on biomarker prioritization. The project has been in two phases. During Phase 1, we conducted a literature review on the accuracy of imaging, CSF, neurophysiological and blood biomarkers in predicting the clinical progression or in defining the underpinning aetiology of main neurocognitive disorders. Evidence was provided to support the panelists’ decisions. In phase 2, a modified Delphi procedure was implemented, and consensus was reached at a threshold of 70% agreement, or 50%+1 when a question required rediscussion.Results:In phase 1, 167 out of 2,200 screened papers provided validated measures of biomarker diagnostic accuracy compared with a gold standard or in predicting progression or conversion of MCI to the dementia stage (i.e., MRI, CSF, FDG-PET, DaT-imaging, amyloid-PET, tau-PET, and myocardial MIBG-scintigraphy and EEG). During phase 2, panelists agreed on the clinical workspace of the workflow, the stage of application, and the patient age window. The workflow is patient-centered and features three levels of assessment (W): W1 defines eleven clinical profiles based on integrated results of neuropsychology, MRI atrophy patterns, and blood tests; W2 describes the first-line biomarkers according to W1 versus clinical suspicion; and W3 suggests the second-line biomarkers when the results of first-line biomarkers are inconsistent with the diagnostic hypothesis, uninformative or inconclusive. CSF biomarkers are first-line in the suspect of Alzheimer’s disease (AD) and when inconsistent neuropsychological and MRI findings hinder a clear diagnostic hypothesis; dopamine SPECT/PET for those leading to suspect Lewy body spectrum. FDG-PET is first-line for the clinical profiles leading to suspect frontotemporal lobar degeneration and motor tauopathies and is followed by CSF biomarkers in the case of atypical metabolic patterns, when an underlying AD etiology is conceivable.Conclusions:The workflow will promote consistency in diagnosing neurocognitive disorders across countries and rational use of resources. The initiative has some limitations, mainly linked to the Delphi procedure (e.g., kickoff questions were driven by the moderators, answers are driven by the Delphi panel composition, a subtle phrasing of the questions may drive answers, and 70% threshold for convergence is conventional). However, the diagnostic workflow will be able to help clinicians achieve an early and sustainable etiological diagnosis and enable the use of disease-modifying drugs as soon as they become available.

Amyotrophic lateral sclerosis with respiratory failure and dysautonomia: a case report.

A 58-year-old male presented with left lower limb limping, difficulty climbing stairs, and left foot weakness, followed by right upper limb weakness and was diagnosed with ALS and received edaravone and riluzole treatment. He presented again with right lower limb weakness, shortness of breath, and wide fluctuations in blood pressure, leading to ICU admission with new diagnosis of ALS with dysautonomia with respiratory failure and was managed with non-invasive ventilation, physiotherapy, and gait training exercises. ALS is a progressive neurodegenerative disease affecting motor neurons but non-motor symptoms can also occur, including dysautonomia, which can result in blood pressure fluctuations. Dysautonomia in ALS is caused by several mechanisms such as severe muscle atrophy, prolonged ventilatory support, and upper and lower motor neuron lesions. Management of ALS involves giving a definitive diagnosis, providing nutritional support, using disease-modifying drugs such as riluzole and non-invasive ventilation to improve survival and quality of life. Early diagnosis is essential for effective management of the disease. Early diagnosis, use of disease-modifying drugs, non-invasive ventilation, and maintaining the patient's nutritional status are crucial for managing ALS which can have non-motor symptoms as well.

Opioid Legislation in Patients With Inflammatory Bowel Disease: A State-wide Retrospective Cohort Study.

Indiana State opioid prescription legislation has been shown to decrease overall opioid prescriptions. However, this effect has not been studied in specific diseases associated with chronic pain such as inflammatory bowel disease (IBD). We aimed to determine the effect of state opioid prescription legislation on opioid prescribing patterns in IBD. A retrospective cohort analysis using an interrupted time-series from December 15, 2010 to July 1, 2018, with 2 time periods separated by Title 844 of the Indiana Administrative Code, in a statewide health care system capturing the majority of the state's population including all adult patients with IBD. The primary outcome was opioid prescription rate per person-year. In total, 9436 patients met inclusion criteria. After legislation, the total number of opioid orders per patient-year continued to increase (0.543, 95% CI, 0.528-0.558, to 0.663, 95% CI, 0.654-0.672), with fewer scripts from the emergency department (0.113, 95% CI, 0.106-0.120, to 0.092, 95% CI, 0.088-0.095) and more from outpatient providers (0.303, 95% CI, 0.292-0.314 to 0.432, 95% CI, 0.424-0.439). There were increases in biologic (0.206, 95% CI, 0.197-0.215 to 0.517, 95% CI, 0.509-0.525) and steroid (0.182, 95% CI, 0.173-0.190 to 0.237, 95% CI, 0.232-0.243) prescriptions per person-year following legislation. Factors associated with heavy opioid use included chronic steroids (odds ratio, 5.030; 95% CI, 4.176-6.054), history of IBD-related surgery (odds ratio, 2.807; 95% CI, 2.367-3.323) and current smoking (odds ratio, 2.650; 95% CI, 2.223-3.158). Despite legislation and the increased use of disease-modifying drugs, statewide opioid prescriptions continued to increase. The increase in opiate use, high steroid use, and significant health care utilization suggests poor underlying disease control.

Multiple sclerosis in pregnancy. Treatment options and outcomes: a review

Background. Women are commonly diagnosed with multiple sclerosis during reproductive age. There is need for disease control management during pregnancy, taking into consideration potential maternal and fetal risks. This review article aims to summarize what is acknowledged so far regarding treatment options of multiple sclerosis and outcomes in pregnancy, providing up-to-date information. Methods. In order to write this review a comprehensive literature electronic search for journal articles and guidelines regarding multiple sclerosis during pregnancy was undertaken. Results and conclusion. Multiple sclerosis management in pregnancy is a challenging issue. The use of disease-modifying drugs has improved both the course of the disease and the attitude towards pregnancy in patients living with multiple sclerosis. Pregnancy appears to have a protective effect on disease activity, particularly during the third trimester.

188 Structural differences in access to neurological healthcare in Northern Ireland: a neurodisparity index

Disparities in management of neurological patients should be minimal in a universal healthcare system. Northern Ireland has one neuroscience centre but no neurology centres. We have devised an easily- applied neurodisparity index (NDI) to measure population equity of neurological healthcare. NDI=number of patients managed per 105 population per Trust/number of patients managed per 105 population of the tertiary centre Trust. NDIs <0.75 and >1.25 were arbitrarily designated as neurodisparities.NDIs were calculated between 2013–2016 for intravenous thrombolysis (eight centres) or mechanical thrombectomy (one centre) for acute ischaemic stroke (AIS), disease modifying drug use for multiple sclerosis (>10 centres) and admissions to a neuroscience neurology ward (n=1) to determine the source and extent of neurodisparity.Amalgamated NDIs for non-tertiary centre trusts were: 0.36 for mechanical thrombectomy for AIS; 0.79 for intravenous thrombolysis for AIS; 1.1 for disease modifying treatment for multiple sclerosis and 0.48 for patient admissions to the tertiary neurology ward. Individual Trust data demonstrated a geographical gradient for mechanical thrombectomy and regional ward admissions.Neurodisparities in Northern Ireland are most marked for mechanical thrombectomy and regional neurology ward admissions. Commissioners should be aware that geography and time-dependent man- agement can exacerbate neurodisparities. Extra resources are required to address such neurodisparities.markmccarron@doctors.org.uk

Epidemiology of hereditary transthyretin amyloidosis in the northernmost region of Sweden: a retrospective cohort study

Introduction Epidemiological data on hereditary transthyretin (ATTRv) amyloidosis from the northernmost region of Sweden (Norrbotten) are sparse. Methods We reviewed the medical records of all incident cases of ATTRv amyloidosis in Norrbotten between 2006 and 2018. Official population and mortality statistics were used to estimate incidence rates and standardised mortality ratios (SMRs). Results Ninety-three patients were diagnosed with ATTRv amyloidosis between 2006 and 2018 (median age, 72.8 years; 68.8% men; 95.7% Val30Met [p.Val50Met] mutation). The incidence rate per 100,000 persons and year increased from 1.50 (95% confidence interval [CI], 0.84–2.47) cases in 2006–2009 to 4.92 (95%CI, 3.46–6.78) cases in 2016–2018. The SMR in the ATTRv amyloidosis cohort was 2.64 times higher than in the general population in 2006–2018 (95%CI, 1.78–3.77). However, there were indications of lower SMRs over time (2006–2012, 2.96 [95%CI, 1.73–4.74]; 2013–2018, 2.32 [95%CI, 1.23–3.96]) and by use of disease-modifying drugs (no, 3.21 [95%CI, 1.87–5.13]; yes, 2.09 [95%CI, 1.08–3.64]). Conclusion The incidence of ATTRv amyloidosis increased 3-fold in Norrbotten between 2006 and 2018, most likely due to a previous underdiagnosis – with suggestions of lowered mortality during later years, possibly due to the introduction of disease-modifying drugs.

Use of disease-modifying drugs (tocilizumab, tofacitinib, and baricitinib-a biological or synthetic target specific) in patients hospitalized with COVID-19.

Use of disease-modifying drugs (tocilizumab, tofacitinib, and baricitinib-a biological or synthetic target specific) in patients hospitalized with COVID-19.

Spotlight on the November 9 Issue

#### Notable in Neurology This Week This issue features an article that examines the association of the use of disease-modifying drugs in people with multiple sclerosis and the severity of coronavirus disease 2019 (COVID-19) infection; another investigates the prevalence and incidence of treated epilepsy in New Zealand children, focusing on ethnicity and socioeconomic status. This issue also includes the first of a series of articles that forecast what the field of neurology will look like in 2035. ### Mechanisms of Network Changes in Cognitive Impairment in Multiple Sclerosis ![Graphic][1]</img> This … [1]: /embed/inline-graphic-1.gif

Use of disease-modifying drugs in diabetic patients with heart failure with reduced ejection fraction.

Type 2 diabetes mellitus and heart failure are closely related, patients with type 2 diabetes mellitus have a higher risk of developing heart failure, and those with heart failure are at increased risk of developing type 2 diabetes. Although no specific randomized clinical trials have been conducted to test the effect of cardiovascular therapies (drugs and/or devices) in diabetic patients with heart failure, a lot of evidence shows that all interventions effective in improving prognosis in patients with heart failure reduced ejection fraction are equally beneficial in patients with and without diabetes. However, the use of disease-modifying drugs in patients with diabetes and heart failure reduced ejection fraction is a clinical challenge due to the increased risk of adverse effects. For example, β-blockers are underutilized in diabetic patients due to the theoretical unfavorable effects on glucose metabolism as well as the use of drugs that interact with the renin-angiotensin system can be challenged in patients with diabetic nephropathy because of the risk of hyperkalemia. This review outlines the current use of disease-modifying drugs in diabetic patients with heart failure reduced ejection fraction. In addition, the role of novel pharmacologic agents as type 2 sodium-glucose co-transporter inhibitors (SGLT2ii) is discussed.

Response to hepatitis B vaccine in patients with multiple sclerosis: preliminary data

Background Studies in different autoimmune pathologies report a lower response rate (immunogenicity) to vaccinations than in the general population. Our objective is to analyze the immunogenicity of the vaccine against hepatitis B virus (HBV) in patients with multiple sclerosis (MS). Methods In a single prospective cohort of MS patients with negative HBV serology, hepatitis B (rDNA) B vaccine was administered at 0, 1 and 6 months. Immunogenicity was analyzed by the determination of antibodies to surface antigens of HBV. We considered a patient as a responder if antibodies level was higher than 10 IU/L. Posterior analysis of immunogenicity was conducted by demographic variables (e.g. MS phenotype, EDSS) and use of disease-modifying drugs (DMTs). Results Vaccination study of 251 patients: 160 of them were sero-negative (63.7%). Patients vaccinated: 99. Overall response: 74.1%. No significant relationship by sex (female 77.6% responders, male 68.8%) and MS phenotype (relapsing forms 74.3% responders, secondary progressive 50%). Variables associated with significantly lower immunogenicity were: age (>55 years), EDSS score (median: non-responders=3.0, responders=1.0), number of relapses and treatment with fingolimod (28.6% responders, n=7). Anti-CD20 therapies showed lower vaccine response (50%), but were not very represented in our sample (n=2). Immunogenicity with other DMTs: interferon/glatiramer 69.6% (n=23), teriflunomide 71.4% (n=14), dimethylfumarate 92.3% (n=13), natalizumab 100% (n=7). Conclusion The overall immunogenicity of our sample is lower than that reported in the general population (74 vs >86%), as in other autoimmune diseases. Preliminary data show a lower immunogenicity with older age, higher EDSS score, number of relapses and fingolimod use.

Use of disease-modifying drugs during pregnancy and breastfeeding.

The fact that multiple sclerosis (MS) predominantly affects women has been recognized for many years. As the age at diagnosis is decreasing, and treatment options are becoming more complex, increasing numbers of women are facing decisions about the use of disease modifying therapy (DMT) in and around pregnancy. New data are rapidly becoming available, particularly regarding the safety of therapies in both pregnancy and breastfeeding. Effective treatment and suppression of relapses is key to ensuring good outcomes in the longer term for the woman, however this must be balanced against individual risk of relapse and risks to the fetus. Women should be advised that it is possible to breastfeed while taking selected DMT. In this review, we discuss evidence surrounding the safety of DMTs in both pregnancy and breastfeeding, and use this knowledge to suggest approaches to pregnancy and family planning in women with MS.

Characteristics of a population-based multiple sclerosis cohort treated with disease-modifying drugs in a universal healthcare setting

ABSTRACT Background: Relatively little is known about the use of disease-modifying drugs (DMDs) for multiple sclerosis (MS) in the population-based universal healthcare setting. This study aimed to describe the characteristics of a population-based cohort with MS and their DMD exposure in four Canadian provinces. Methods: We identified all adults (aged ≥18 years) with MS using linked population-based health administrative data. Individuals were followed from the most recent of their first MS or demyelinating event or 1 January 1996(study entry), to the earliest of death, emigration, or 31 March 2018(study end). Cohort characteristics examined included sex, age, socioeconomic status, and comorbidity burden. Results: Overall, 10,418/35,894 (29%) of MS cases filled a DMD prescription during the 22-year study period. Most were women (n = 7,683/10,418;74%), and 17% (n = 1,745/10,418) had some comorbidity (Charlson Comorbidity Index≥1) at study entry. Nearly 20% (n = 1,745/10,418) were aged ≥50 when filling their first DMD; the mean age was 39.6 years. Conclusions: Almost 1 in 6 people with MS had at least some comorbidity, and nearly 1 in 6 were ≥50 years old at the time of their first DMD. As these individuals are typically excluded from clinical trials, findings illustrate the need to understand the harms and benefits of DMD use in these understudied groups.