Novartis Research Articles

123-LB: Implementing a Multidisciplinary Model of CGM Care in Real-World Pharmacy Practice—A Clinical Consensus for Canadian Pharmacists

Background: Continuous glucose monitoring (CGM) devices have transformed diabetes care, but there is a lack of guidance for pharmacists to follow when onboarding patients to begin using CGM systems. Our study aimed to develop a blueprint for best practices for pharmacists to support people living with diabetes (PWD) using CGM systems. Methods: We used a modified DELPHI process to gather insights from 11 Key Opinion Leaders (KOLs) across Canada, including two endocrinologists, one family physician, and eight pharmacists. Consensus was reached for each criterion when 75% agreement was achieved. Criteria for CGM device initiation, short-term or episodic CGM use, and best practices for CGM onboarding and monitoring were developed based on the results. Results: Amongst the ideal candidates for CGM use are PWD using insulin, those with type 1 diabetes, individuals not reaching their A1C target, those experiencing frequent hypoglycemia, pregnant individuals, and others at risk of hypoglycemia. Best practices for onboarding and monitoring included shared decision-making conversations, a comprehensive overview of cost and coverage options, customized alerts and alarms, and timely follow-up sessions. Discussion: The KOL group ensured a comprehensive and diverse perspective. The developed blueprint provides a valuable resource for pharmacists to improve the use of CGM devices and enhance diabetes management for their patients. Incorporating these best practices into clinical practice has the potential to transform diabetes care and improve outcomes. Disclosure A. S. Sihota: Consultant; Novo Nordisk Canada Inc., Other Relationship; Becton, Dickinson and Company. S. Sivapalan: Advisory Panel; Novo Nordisk, Pfizer Inc., AstraZeneca, Consultant; Pear Healthcare Solutions Inc., Other Relationship; Boehringer Ingelheim (Canada) Ltd., GlaxoSmithKline plc., Novo Nordisk, Bristol-Myers Squibb Company, Pfizer Inc., AbbVie Inc., Ferring Pharmaceuticals, AstraZeneca. T. Smith: Advisory Panel; Novo Nordisk Canada Inc., Dexcom, Inc., Emergent Biosolutions. I. Halperin: Advisory Panel; Sanofi, Speaker's Bureau; 3Boehringer Ingelheim Canada Ltd. /Ltée, Abbott Diabetes, Dexcom, Inc., Novo Nordisk. A. B. Jain: Advisory Panel; Abbott, Amgen Canada, Dexcom, Inc., AstraZeneca, Novo Nordisk, Bayer Inc., Insulet Corporation, Takeda Canada, Boehringer Ingelheim (Canada) Ltd., Eli Lilly and Company, Research Support; Abbott, Amgen Canada, Novo Nordisk, Speaker's Bureau; Abbott, Amgen Canada, Dexcom, Inc., AstraZeneca, Novo Nordisk, Bausch Health, Canada, Boehringer Ingelheim (Canada) Ltd., Eli Lilly and Company, Pfizer Inc. A. Chin: Other Relationship; Abbott Diabetes, BMO Bank of Montreal, Diabetes Canada, Dexcom, Inc., Roche Diabetes Care, Tandem Diabetes Care, Inc., Research Support; Novavax, Centricity Research. W. Chow: Advisory Panel; GlaxoSmithKline plc., Pfizer Inc., Speaker's Bureau; Abbott Diagnostics, AstraZeneca, Bayer Inc., Bausch Health, Canada, Boehringer Ingelheim (Canada) Ltd., Eisai Inc., Novo Nordisk. S. Jin: Advisory Panel; Dexcom, Inc., Eisai Inc., Novo Nordisk Canada Inc., Board Member; Wounds Canada, Consultant; Abbott Diabetes, Boehringer Ingelheim Pharmaceuticals Inc., Canadian Collaborative Research Network, Diabetes Canada, GlaxoSmithKline plc., HLS Therapeutics Inc., MDBriefcase, Novo Nordisk Canada Inc., AstraZeneca, Speaker's Bureau; Eisai Inc., Dexcom, Inc., Novo Nordisk Canada Inc. T. Molberg: None. S. Patil: None. R. Siemens: Consultant; Canadian Collaborative Research Network, Novartis Canada, AstraZeneca, Montmed, Sanofi, MDBriefcase, Other Relationship; Abbott Diabetes, Amgen Canada, Boehringer Ingelheim and Eli Lilly Alliance, GlaxoSmithKline plc., HLS Therapeutics, Novo Nordisk, Dexcom Canada, Diabetes Canada. Funding Dexcom Canada

637-P: Sex-Specific Associations between Fatty Acid–Derived Oxylipins and Executive Function in T2DM

T2DM increases the risk of cognitive decline, especially in women. Sex-specific associations between lipids and cognition have been reported, though underlying mechanisms remain unclear. Disruptions in the cytochrome P450-soluble epoxide hydrolase (CYP450-sEH) pathway have been linked to both T2DM and cognitive dysfunction. CYP450s convert long-chain polyunsaturated fatty acids into epoxides which are anti-inflammatory and help resolve inflammation, however sEH metabolizes these into inactive or cytotoxic diols, limiting their benefits. We hypothesized that oxylipin epoxides and diols of arachidonic acid (AA) and docosahexaenoic acid (DHA) would be associated with cognition in people with T2DM, particularly in women. Women and men with T2DM were recruited as part of the study. Twenty-two fasting serum free oxylipins were quantified by ultra-high performance liquid chromatography tandem mass spectrometry. Executive function was assessed using a composite z-score from the following tests: Stroop Colour-Word Interference Victoria Version, FAS Verbal Fluency, Digit Symbol Substitution, and Trails Making Test Part B. All analyses controlled for age, sex, BMI, HbA1c and years of education. Among 72 individuals with T2DM (mean age 61.8±9.2, mean HbA1c 7.4±0.1%, 53% women), demographic characteristics, oxylipin concentrations and cognitive performance did not differ between women and men. Some CYP450-derived epoxides of DHA and AA were associated with lower executive function scores in women, but with higher scores in men. Epoxide × sex interactions were found for 3 of 4 DHA epoxides (16(17) [F=20.2, p<0.001]; 13(14) [F=8.5, p=0.005]; and 10(11) [F=7.4, p=0.009]), and for the 14(15) AA epoxide [F=3.9, p<0.05]). Circulating concentrations of the corresponding diols were not associated with executive function. These associations between epoxides and executive function suggest a sex difference in the relevance of the CYP450 pathway to cognitive performance in T2DM. Disclosure S.Ryoo: None. B.R.Shah: None. J.Gilbert: Speaker's Bureau; Abbott, AstraZeneca, Amgen Canada, Bayer Inc., Boehringer Ingelheim (Canada) Ltd., Sanofi, Dexcom, Inc., Eli Lilly and Company, HLS Therapeutics Inc., Novo Nordisk Canada Inc. A.Assal: None. I.Halperin: Advisory Panel; Sanofi, Speaker's Bureau; 3Boehringer Ingelheim Canada Ltd./Ltée, Abbott Diabetes, Dexcom, Inc., Novo Nordisk. A.Taha: None. W.Swardfager: None. N.Z.Anita: None. C.Major-orfao: None. W.Lin: None. S.Noor: None. F.Kwan: None. K.L.Lanctôt: Consultant; Exciva, GW Pharmaceuticals, ICG Farma, Merck Sharp & Dohme Corp., Novo Nordisk, Sumitomo Pharma Co. Ltd., Other Relationship; BioXcel, Cerevel Therapeutics, H Lundbeck A/S. N.Herrmann: None. P.Oh: Advisory Panel; Novartis Canada. Funding Canadian Institutes of Health Research; Banting & Best Diabetes Centre; National Institute of Diabetes and Digestive and Kidney Diseases

1275-P: Incident Diabetes Before and During the COVID-19 Pandemic among Youth in Kaiser Permanente Southern California

Background: Prior research found increases in type 1 and type 2 diabetes (T1D/T2D) among youth during the COVID-19 pandemic but did not focus on age, sex, or race/ethnicity variation. We examined incidence rates from 2016-2021 in Kaiser Permanente Southern California (KPSC), a large, integrated healthcare delivery system. Methods: KPSC members <20 years old, with no diabetes prior to their incidence year were followed using electronic health records for diabetes defined using diagnoses, labs, and diabetes medications. We calculated age- and sex-standardized incidence rates per 100,000 person-years (PY) for T1D and T2D between 2016-2021 overall and by age, sex, and race/ethnicity. We used Poisson regression to calculate incidence rate ratios (IRR) comparing 2020-2021 to 2016-2019. Results: Incidence of T1D increased from 18.5/100,000 PY in 2016-2019 to 22.4/100,000 PY in 2020-2021 with increased IRR among 10-19-year-olds, both sexes, and Hispanic individuals. (Table) Incidence of T2D increased from 14.8/100,000 PY in 2016-2019 to 24.7/100,000 PY in 2020-2021 with increased IRR among 10-19-year-olds, both sexes, and those with non-Hispanic Black, Hispanic, and other/unknown race/ethnicity. Conclusion: Incidence of both T1D and T2D increased following the start of the pandemic. Future research to understand potential underlying physiologic and behavioral risk factors is warranted. Disclosure M.T.Mefford: None. R.Wei: None. E.Lustigova: None. J.P.Martin: None. K.Reynolds: Research Support; Novartis Pharmaceuticals Corporation.

1003-P: Cost of Care for Patients with Diabetic Kidney Disease in Veterans Health Administration

Introduction: Diabetic kidney disease (DKD) represents a substantial burden on the Veterans Health Administration (VHA). We calculated the cost of DKD care for US Veterans from the healthcare system perspective. Methods: Veterans with type 2 diabetes (T2D) in 2015-2021 were identified using diagnosis codes, prescription records, and problem lists. We identified prevalent and incident DKD stages based on urine albumin, urine protein, and eGFR, and following the Kidney Disease Improving Global Outcome definitions. Aggregate all-cause monthly healthcare costs per patient for managing each DKD stage (ie, stages 1 through 5) were estimated by summing patient-level VHA costs in incident DKD stages from January 2018 until December 2021. Summary statistics include descriptive median and interquartile ranges of per-patient per-month [PPPM] cost. All costs were inflated to 2022 US dollars (USD) based on the Consumer Price Index of all items for urban consumers. Results and Conclusion: Out of two million US Veterans with T2D, we identified 401,214 DKD patients with 1+ incident stage progression in the follow-up period. Median PPPM all-cause healthcare cost increased exponentially from $748 at Stage 1 to $2,661 at Stage 5 (Figure). Interventions targeting patients with rapid DKD progression could markedly decrease the burden of DKD in US Veterans. Disclosure K.Kim: Research Support; Renalytix, GRAIL (acquired by Illumina in 2021), AstraZeneca. J.L.Crook: None. C.S.Lu: None. R.E.Nelson: None. H.Nyman: None. J.Lafleur: Research Support; Renalytix, Genentech, Inc., Novartis Pharmaceuticals Corporation.

1375-P: Child-Reported Food Security in Children with Type 1 Diabetes—Association with Glycemic Control and Mental Health Symptoms Independent of Household Food Security

Introduction: Typically, caregivers report on household food security (FS), but children’s experiences may differ from caregiver reports. We assessed if child-reported food insecurity (FI) was associated with glycemic control, acute complications of diabetes, depressive symptoms, and disordered eating in children with type 1 diabetes (T1D), independently from household FS. Methods: In a cross-sectional analysis of the multicenter SEARCH for Diabetes in Youth Study (Phase 4, 2016-2019), including 601 children age 10-17 years with T1D, household FS and child-reported FS were assessed using the 18-item Household Food Security Survey Module and the six-item Child Food Security Assessment questionnaire. Age-stratified (10-13, 14-17) regression models were performed to estimate independent associations, adjusting for sociodemographic and clinical factors and household FS. Results: FI was reported by 13.1% (n=79) of children and 15.6% (n=94) of caregivers. Among child-caregiver dyads, 82.5% (n=496) of reports were concordant and 17.5% (n=105) discordant, Cohen’s kappa = 0.3. Child-reported FI was not independently associated with hemoglobin A1c, diabetic ketoacidosis, and hypoglycemia, including in age-stratified analyses. Child-reported FI was independently associated with elevated odds of depressive symptoms (OR 3.6, 95% CI 1.3-10.3) and disordered eating (OR 2.5, 95% CI 1.4-4.6) compared to FS; these associations remained in both age groups for disordered eating and in the older group for depressive symptoms. Conclusion: Children with T1D may experience FI differently than caregivers. Child-reported FI was independently associated with depressive symptoms and disordered eating and thus may be an important attribute to assess in addition to household FS in children with T1D. Disclosure E.F.Julceus: None. B.A.Reboussin: None. K.Reynolds: Research Support; Novartis Pharmaceuticals Corporation. C.Pihoker: None. A.D.Liese: None. E.A.Frongillo: None. J.A.Mendoza: None. K.A.Sauder: None. F.Malik: None. E.T.Jensen: Consultant; Regeneron. L.M.Dolan: None. A.Bellatorre: None. D.Dabelea: None. Funding National Institutes of Health (R01DK117461, 1R01DK127208, 1UC4DK108173, T32GM081740)

259-OR: Arterial Stiffness and Diabetes-Associated Complications in the SEARCH for Diabetes in Youth Study

Arterial stiffness and vascular complications contribute to the burden of disease in diabetes, and it is unclear how they relate to each other. The relationship between arterial stiffness, an early marker of cardiovascular disease, and microvascular complications has not been comprehensively assessed in youth-onset diabetes. This study included 1226 individuals (mean age 22.8 years, 58% female, 53% Non-Hispanic White, 22% Non-Hispanic Black, 20% Hispanic) with type 1 (n=999) and type 2 (n=227) diabetes. Arterial stiffness measures included pulse wave velocity for carotid-femoral (PWVcf), carotid-radial (PWVcr), and femoral-foot (PWVff) and augmentation index (AIx). Microvascular complications included diabetic kidney disease, peripheral neuropathy, and retinopathy. Logistic regression was used to analyze associations between arterial stiffness and microvascular complications. PWVcf and AIx were associated with higher odds of having any microvascular complication, p<0.05 (Table). PWVcf, PWVff, and AIx were each associated with diabetic kidney disease. PWVcf was associated with peripheral neuropathy and PWVcr and AIx were associated with retinopathy. Arterial stiffness is related to diabetes microvascular complications in youth-onset diabetes. Future work will determine whether arterial stiffness is a marker for early onset and progression of microvascular complications. Disclosure R.Brady: None. L.Sancrainte: None. A.S.Shah: None. E.M.Urbina: Advisory Panel; Astellas Pharma Inc., Other Relationship; Targus Medical, Inc. Z.Gao: None. L.M.Dolan: None. D.Dabelea: None. E.Lustigova: None. A.K.Mottl: Advisory Panel; Bayer Inc., Chinook Therapeutics Inc., Consultant; Bayer Inc., Research Support; Bayer Inc., Alexion Pharmaceuticals, Inc., Pfizer Inc., Boehringer Ingelheim Inc., Calliditas. C.Pihoker: None. K.Reynolds: Research Support; Novartis Pharmaceuticals Corporation. Funding National Institute of Diabetes and Digestive and Kidney Diseases (1R01DK127208-01); Centers for Disease Control and Prevention (00097, DP-05-069, DP-10-001)

992-P: Coronary Artery Calcium Scoring to Improve Statin Use in Adults with Type 2 Diabetes Not on Statin Therapy—Anticipated Cost Utility

Background: Statin use in adults with diabetes is sub-optimal. Coronary artery calcium (CAC) scoring can provide a visual quantification of CV risk and may improve statin initiation and long-term use. Objective: Estimate the cost-utility of CAC scoring compared to traditional CV risk counselling only, for improving statin use in adults with diabetes who have not previously had a CV event, and are not on statin therapy. Methods: Probabilistic Markov model from a health system perspective, over a 10-year time horizon. The effectiveness of CAC scoring was obtained from the EISNER trial. Outcomes included acute coronary syndrome (ACS), stroke, heart failure, mortality, and radiation-induced cancer. Outcome rates and costs were obtained from an analysis of Alberta administrative data, and from publicly available sources. The base population modeled was men age 60, with additional analyses for other age, sex-groups and scenarios. Results: CAC scoring increased statin use to 44% vs 25% with traditional CV risk counselling only. There were 8.4 fewer ACS, 5.5 fewer strokes, and 1.6 fewer deaths / 1000 individuals. Costs were slightly lower (-$14, 95% CI [-$402-(+$208)]) (CAD), for a small benefit in quality-adjusted life years (+0.01, [0.00-0.02]), with mean ICER of $7,132 (-$27,828-(+$65,513)) / QALY. At a willingness-to-pay of $50,000 / QALY, CAC was cost-effective in 95% of trials. CAC scoring was not cost-effective in younger men or in women, but could be cost-effective or cost savings in men (age ≥ 40) and older women (age ≥ 60) who refuse statin therapy, but would be persuaded by personalized evidence of coronary artery disease (CAC score > 10). Conclusion: CAC scoring may be cost-effective in older men not receiving statins, and in men or older women who agree to use statins if shown personalized evidence of coronary artery disease. Disclosure D.Lau: None. G.J.Pearson: Advisory Panel; HLS Therapeutics Inc., Novartis Pharmaceuticals Corporation, Pharmacience, Consultant; Trimedic Therapeutics. P.Raggi: None. S.Klarenbach: Research Support; Bayer Inc., Allergan, GlaxoSmithKline plc., CSL Behring, Lundbeck, University Hospital Foundation (University of Alberta), Purdue Canada.

858-P: Recruitment Strategies for a Cellular Therapy Study for Type 1 Diabetes

Mesenchymal stem cells may be a novel T1D treatment based on immunoregulatory and tissue-protective properties. Therefore, an NIDDK sponsored prospective, single center, double blind study of MSCs for new onset T1D (NCT04061746) has generated significant social media interest. This trial is hard to enroll because of a narrow age range (18-30 years) and requirement of a new onset diagnosis (6 months). We evaluated the impact of social media tools, clinicaltrials.gov advertisement, and medical record review (EPIC) to define the optimal screening process for this and future trials. Through clinicaltrials.gov the study piqued the interest of 173 participants. Additionally, the study team has pre-screened 346 patients from an EPIC generated report. Among the 22 patients consented, referrals were received from physicians (N=5), clinicaltrials.gov (N=13), and EPIC reports (N=4). Among those discovered via EPIC list, we depicted the main reasons for study ineligibility (Fig. 1). The study recently launched a social media campaign in December 2022, initially reaching a total of 16,593 viewers. 4,475 viewers (26.97%) interacted with the campaign, and 2 (0.012%) were potentially interested in follow up from the research team. We conclude that clinicaltrials.gov, medical record review, and physician referrals are all critical to screening for new-onset diabetes studies. Other T1D studies might benefit from utilizing these strategies. Disclosure L.Benn: None. W.Gou: None. P.J.Nietert: None. M.Cornier: Consultant; Novo Nordisk, Alnylum, Letsgetchecked, Research Support; Novartis Pharmaceuticals Corporation, Amgen Inc., Kaneka. S.Norton: None. C.Strange: None. H.Wang: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (1R01DK118529, DK120394, DK105183, DK125454); U.S. Department of Veterans Affairs (I01BX004536)

Report of a chronic myeloid leukemia registry in a low-and middle-income setting.

7054 Background: Treatment of chronic myeloid leukaemia (CML) in Kenya has been supported since the year 2002 by a collaboration between the Max Foundation and Novartis Pharmaceuticals in the Glivec International Patient Assistance Program (GIPAP). In November 2020 this was transitioned to Max Access Solutions (MAS) that brought in the Ministry of Health as a partner. A broad range of BCR-ABL tyrosine kinase inhibitors are available. We wanted to describe epidemiology, treatment and outcome of CML in the country. Methods: Patients’ records were reviewed and data entered in a database. Key variables included age, sex, BMI, diet, disease phase at diagnosis, treatment, and outcome. Continuous variables were summarized using mean (standard deviation) or median (interquartile range). Categorical variables were summarized using counts and percentages. Bivariate comparisons of treatment outcome were done using chi-square or Fisher’s exact test. Analysis of variance (ANOVA) or Kruskal-Wallis test was used for continuous variables. Results: 1347 patients-males 748 (55.5%), females 599 (44.5%). Mean age was 44.5 years. Seventy (9.0%) were underweight, 88 (11.4%) obese. Mean body surface area (BSA) was 1.75m2. Chronic phase cases were 1177 (96.2%), accelerated phase 46 (3.8%), blastic phase 1 (0.1%). Mean bone marrow blast count was 5.25%, BCR-ABL/ABL was 63.7%, haemoglobin 10.8g/dl, total wbc count 225 x 109/litre, platelets 392.5 x 109/litre. Imatinib was administered upfront to 1319 patients (99.8%). Two hundred and six (15.3%) were switched to second line; 100 (48.8%) to dasatinib, 50 (24.4%) to bosutinib. Transformation was registered in 26 cases (1.9%) - accelerated in 13 (72.2%), blastic in 5 (27.8%), 4 (80.0%) being myeloid and 1 (20%) lymphoblastic. Those alive are 1151 (85.4%) and 185 (13.7%) lost to follow-up. Deaths were recorded in 11 (0.8%). Those with lower BSA were more likely to die (p = 0.01). Conclusions: CML in Kenya occurs at a younger age-group with a slight male preponderance. With availability of a range of BCR-ABL tyrosine kinase inhibitors, treatment outcome is close to what is documented in high-income settings.

Protecting Mothers and Babies Through Research

CBR is employed by and is a stockholder of Novartis Pharmaceuticals Corporation. No.

Quality care of patients with HR+/HER2- breast cancer: Insights from an implementation science program.

e18756 Background: Oral oncolytics have transformed the treatment landscape of HR+/HER2- breast cancer, shifting the responsibility for medication adherence and side effect management to patients. To optimize patient outcomes, collaborative patient-provider education on treatment expectations, adverse event management, and shared decision-making is imperative. Methods: From 11/2021 to 2/2022, HR+/HER2- breast cancer patients (N = 55) and health care professionals (HCPs) (N = 69) who treat breast cancer from 5 community practices were surveyed on attitudes, values, and challenges related to treatment, adherence, and adverse event management on oral therapies. HCPs (N = 59) participated in audit-feedback (AF) sessions to reflect on their own practice and develop action plans to improve care, which were implemented in subsequent collaborative patient-provider learning sessions. Informed by survey findings and insights from patient focus groups a, a point-of-care oral oncolytic toolkit was disseminated to support patients and providers in effective communication, treatment adherence, and side effect management. Results: In surveys, HCPs and patients reported side effects of medication as the top challenge impacting treatment adherence, with fatigue (33%), nausea/vomiting (28%), and hair loss (28%) the most challenging side effects. Notably, 46% of HCPs reported inadequate time to discuss patient goals, preferences and concerns as the biggest barrier for shared decision-making, and 15% of patients reported their doctor does not always ask about goals, preferences, and concerns. Reflection on survey and focus group insights in AF sessions enabled providers to develop and implement action plans including the provision of patient education resources on medication adherence and side effect recognition and management, scheduling adequate follow-up appointments to ensure side effect management and medication compliance, and engaging in shared decision-making. In patient-provider collaborative sessions, patients demonstrated substantial knowledge gains in how to communicate, recognize, and manage side effects associated with treatment, and providers committed to continuing patient education. Conclusions: Through a combination of a patient and provider survey study, patient focus groups, HCP AF sessions, and collaborative patient-provider learning sessions, action plans and education resources were developed and implemented to support the provision of effective treatment management for HR+/HER2- breast cancer. The methods and findings of this study represent key opportunities for improvement in caring for patients with HR+/HER2- breast cancer. Study Sponsor Statement: This activity is supported by educational grants from Lilly and Novartis Pharmaceuticals Corporation, who had no role in the study design, execution, analysis, or reporting.

Burden of lipoprotein(a) for patients with atherosclerotic cardiovascular disease: A retrospective analysis from the United States.

BACKGROUND: Lipoprotein(a) (Lp(a)) is an inherited, independent, and causal risk factor for atherosclerotic cardiovascular disease (ASCVD). OBJECTIVE: To assess the burden of elevated Lp(a) for patients with ASCVD in a real-world setting in the United States. METHODS: This retrospective cohort study assessed US patients with available Lp(a) measurement and established ASCVD using Optum's Clinformatics Data Mart database (2007-2020). Index date was defined as the first diagnosis of an ASCVD event. Patient demographics, medications, health care resource utilization (HCRU), and occurrence of cardiovascular events were assessed for patients with elevated (≥150 nmol/L) vs normal (≥65 nmol/L) Lp(a) levels, within the first year of index date. HCRU was characterized by inpatient hospitalization, inpatient length of stay (LOS), outpatient visits, and emergency department (ED) visits. All comparative analyses of patients with elevated (≥150 nmol/L) vs normal (≥65 nmol/L) Lp(a) levels within the first year of index date were adjusted for age, sex, baseline statin use, and diabetes. RESULTS: 8,372 patients with ASCVD and Lp(a) measurement in nmol/L were included in this study. Patient demographics and baseline clinical characteristics were similar among those with normal and elevated Lp(a). However, the proportion of patients receiving statins and β-blockers at baseline were significantly higher in the elevated vs normal Lp(a) group (54.76% vs 42.91%, P < 0.0001, and 30.92% vs 27.32%, P = 0.0183, respectively). At 1 year of follow-up, the rates per 100 person-years for ASCVD-related inpatient hospitalizations, outpatient hospitalizations, and ED visits were higher among patients with elevated Lp(a) compared with normal Lp(a) (13.33 vs 9.46, 89.08 vs 85.10, and 2.89 vs 2.29, respectively). The mean LOS per ASCVD-related hospitalization was 7.21 days in the elevated and 6.26 days in the normal Lp(a) group (P = 0.3462). During the 1-year post-index follow-up period, 15% of patients in the elevated Lp(a) group required revascularization compared with 10% of patients in the normal Lp(a) group (P = 0.0002). The odds of composite myocardial infarction, ischemic stroke, and revascularization occurrence of events within the first year of index was significantly higher in the elevated Lp(a) group compared with the normal Lp(a) group (1.46; 95% CI = 1.20-1.77; P < 0.05). CONCLUSIONS: HCRU within the first year of ASCVD diagnosis is substantial among patients with ASCVD and elevated Lp(a). Relatively higher rates of inpatient hospitalizations, increased LOS per hospitalization, and requirement of revascularization procedures within the first year of ASCVD index diagnosis were observed in patients with elevated Lp(a) compared with normal Lp(a) levels. Lp(a) testing in routine clinical practice could help in identification of high-risk patients with ASCVD and play an important role in the overall cardiovascular risk management, aiming to reduce the HCRU associated with ASCVD. DISCLOSURES: Ms Fonseca, Dr Laguna, Dr Itani, Dr Rachel Studer, and Dr Ferber are employees of Novartis Pharma AG, Basel, Switzerland. Ms Byrne is an employee of Novartis AG, Dublin, Ireland. Dr Costa-Scharplatz is an employee of Novartis Sweden AB, Stockholm, Sweden. Dr Heo and Ms Dillon are employees of Genesis Research. Genesis Research was commissioned to conduct the study (data extraction and analysis) on behalf of Novartis Pharma AG.

Alpelisib: a novel PI3K inhibitor for the treatment of breast cancer

Breast cancer is a common malignancy that causes people to die easily, especially for women. HR-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancers occur in more than 70% of patients, who have a driver mutant kinase catalytic subunit alpha (PIK3CA) in the phosphatidylinositol 4, 5-diphosphate 3-kinase gene, resulting in impaired phosphatidylinositol 3-kinase (PI3K) and in 40% of cases, loss of cell growth. However, drug resistance remains a problem in the early stages of endocrine therapy in these patients. And a promising new approach to overcome resistance to autologous treatment in breast cancer is the inhibition of PI3K. Alpelisib is a selection PI3K inhibitor for HR-positive, HER2-negative, PIK3CA patients - with mutant breast cancer that has advanced on autologous treatment. FDA approved alpelisib in 2019 which was produced by Novartis Pharmaceuticals Corporation. It is recommended to take this drug with fulvestrant which is also an estrogen receptor antago-nist that slows the growth of breast cancer. Although alpelisib is an effective drug for the treatment of breast cancer, some adverse reactions may happen, such as stomatitis, nausea, diarrhe, dermatitis, and so on. Sometimes it also causes skin reactions, such as SIS, TEN, EM. Thus, when these serious adverse reactions happen, dosage should be reduced. As a result, some recommendations are provided for patients, and they must follow the instructions in or-der to live a more pleasant life. In this article, the working mechanism, structure, characteris-tics, clinical studies of alpelisib were reviewed and its comparison with other drugs was also provided for reference.

Time-Varying Functional Connectivity of the Hippocampus Is Associated With Cognitive Performance in Multiple Sclerosis Patients (P10-3.014)

<h3>Objective:</h3> To explore hippocampal static (sFC) and time-varying functional connectivity (TVFC) and assess their association with cognition in multiple sclerosis (MS). <h3>Background:</h3> The hippocampus has a key role in cognition. Hippocampal TVFC in MS needs to be further explored. <h3>Design/Methods:</h3> 3T structural and resting-state (RS) functional MRI scans were acquired from 108 MS patients and 63 healthy controls (HC). Subjects underwent neuropsychological evaluation. Sliding-window correlation analysis using the left (L) and right (R) hippocampus as seed regions assessed TVFC, quantified by the standard deviation of connectivity across windows. Mean connectivity indicated sFC. <h3>Results:</h3> MS patients had decreased sFC <i>vs</i> HC between L hippocampus and temporo-parietal regions, and increased sFC between L and R hippocampus and thalamus, precuneus and superior frontal regions. TVFC was decreased in MS patients between L hippocampus and temporo-parietal regions. Conversely, TVFC was increased in MS patients between L and R hippocampus and L pre- and postcentral gyri, cuneus, orbitofrontal cortex and inferior temporal gyrus (ITG). In MS patients, better global cognition correlated with higher TVFC between L hippocampus and L pre- and postcentral gyri (r=0.21–0.28; p=0.04–0.006). Better verbal memory correlated with higher TVFC between L hippocampus and L precentral gyrus (r=0.21, p=0.03), and better visuospatial memory correlated with higher TVFC between L and R hippocampus and L cuneus, pre- and postcentral gyri and ITG (r=0.19–0.23, p=0.02–0.04). Better information processing speed correlated with higher TVFC between L hippocampus and L postcentral gyrus (r=0.21, p=0.03) and with higher sFC between R hippocampus and L superior frontal cortex (SFC) (r=0.21, p=0.03). Finally, better attention scores correlated with higher TVFC between L hippocampus and L temporal cortex (r=0.24, p=0.01) and with higher sFC between R hippocampus and L SFC (r=0.20, p=0.05). <h3>Conclusions:</h3> Increased hippocampal connectivity contributed to explain better cognitive performances in MS, with a peculiar association between higher hippocampal TVFC and better memory scores. <b>Disclosure:</b> Monica Margoni has received research support from MAGNIMS. Paola Valsasina has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for ACCMED. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bristol Myers Squibb . Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi Genzyme. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck. Olga Marchesi has nothing to disclose. Carmen Vizzino has nothing to disclose. Damiano Mistri has nothing to disclose. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, Takeda, and Teva Pharmaceutical Industries. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, Takeda, and Teva Pharmaceutical Industries. Dr. Filippi 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 Springer Nature. The institution of Dr. Filippi has received research support from Biogen Idec, Merck-Serono, Novartis, Roche, Teva Pharmaceutical Industries, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, and ARiSLA (Fondazione Italiana di Ricerca per la SLA). Maria Assunta Rocca has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bayer, Biogen, Bristol Myers Squibb, Celgene, Genzyme, Merck Serono, Novartis, Roche, and Teva. The institution of Maria Assunta Rocca has received research support from Italian Ministry of Health, MS Society of Canada and Fondazione Italiana Sclerosi Multipla.

Timing and Predictors of T2-Lesion Resolution in MOGAD (P13-5.028)

Timing and Predictors of T2-Lesion Resolution in MOGAD (P13-5.028)

Characterization of FTLD spectrum through advanced diffusion-weighted MRI metrics: a connectome approach (P11-6.003)

<h3>Objective:</h3> To investigate structural alterations in brain network of patients within the frontotemporal lobar degeneration (FTLD) spectrum using connectome analysis with advanced diffusion-weighted MRI metrics. <h3>Background:</h3> MRI connectomics is a promising tool to describe network-based degeneration in neurodegenerative diseases. Neurite orientation dispersion and density imaging (NODDI) has shown to provide novel insights on structural connectivity alterations. <h3>Design/Methods:</h3> Thirty-four behavioral-variant frontotemporal dementia (bvFTD), 11 semantic variant primary progressive aphasia (svPPA), 11 nonfluent (nfvPPA) patients and 48 healthy controls underwent multi-shell diffusion MRI. Fractional anisotropy (FA) maps were computed. Intra-cellular Volume Fraction (ICVF) maps were also estimated using NODDI, providing a direct quantification of neurite integrity. Graph analysis and connectomics assessed global and local structural topological network properties and regional structural connectivity. <h3>Results:</h3> Overall, widespread structural changes were observed in bvFTD patients relative to healthy controls and svPPA patients in terms of FA-derived network properties. nfvPPA patients also showed altered FA topological properties at global level compared to healthy controls. Sum of node weights (SN) in the sensorimotor lobe revealed that nfvPPA patients showed an altered connection strength compared to svPPA. Moreover, nfvPPA patients showed a significant decreased FA in the left hemispheric fronto-temporal-insular regions relative to controls. Considering ICVF, more severe alterations compared to FA maps allowed to find differences also between svPPA and nfvPPA patients. ICVF graph analysis measures also showed that svPPA had a lower degree centrality and SN in the temporal lobe compared to controls. <h3>Conclusions:</h3> These findings suggest that conventional diffusion-tensor measures might be sensitive enough to highlight vulnerable connections in the FTLD spectrum. However, ICVF demonstrated to be a more specific biomarker to differentiate FTLD syndromes. Specifically, the benefits emerged in the differentiation between svPPA patients and other groups. <b>Disclosure:</b> Federica Agosta has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Philips. Federica Agosta has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier INC. Silvia Basaia has nothing to disclose. Dr. Facente has nothing to disclose. Ms. Cividini has nothing to disclose. Dr. Spinelli has nothing to disclose. The institution of Elisa Canu has received research support from Italian Ministry of Health . Dr. Castelnovo has nothing to disclose. Giuseppe Magnani has nothing to disclose. Dr. Caso has nothing to disclose. Paola Caroppo has nothing to disclose. Sara Prioni has nothing to disclose. Miss Villa has nothing to disclose. Lucio Tremolizzo has nothing to disclose. Dr. Appollonio has nothing to disclose. Dr. Silani has nothing to disclose. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, Takeda, and Teva Pharmaceutical Industries. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, Takeda, and Teva Pharmaceutical Industries. Dr. Filippi 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 Springer Nature. The institution of Dr. Filippi has received research support from Biogen Idec, Merck-Serono, Novartis, Roche, Teva Pharmaceutical Industries, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, and ARiSLA (Fondazione Italiana di Ricerca per la SLA).

Effect of RIPK1 Inhibitor, SAR443820, on Serum Neurofilament Light Levels in Patients with Multiple Sclerosis: A Phase 2 Trial Design (P6-3.011)

Effect of RIPK1 Inhibitor, SAR443820, on Serum Neurofilament Light Levels in Patients with Multiple Sclerosis: A Phase 2 Trial Design (P6-3.011)

Identification of Neuropsychological Phenotypes in Pediatric Multiple Sclerosis Using Unsupervised Machine Learning (P12-9.001)

<h3>Objective:</h3> To identify cognitive phenotypes in pediatric multiple sclerosis (MS) using an unsupervised machine learning approach. <h3>Background:</h3> Recent studies identified distinct cognitive phenotypes in adult MS patients using unsupervised machine learning approaches. <h3>Design/Methods:</h3> Fifty-three pediatric MS patients underwent clinical examination including Expanded Disability Status Scale (EDSS) to assess global disability. A comprehensive neuropsychological battery (Selective Reminding Test, Spatial Recall Test, Trail Making Test, Symbol Digit Modalities Test, Semantic verbal fluency test and Phonemic verbal fluency test) was administered to all patients. Raw scores of each test were converted to z-scores according to normative data. Cognitive tests z-scores were included in a k-means cluster analysis to identify cognitive phenotypes. Between-group comparisons of demographic, clinical and cognitive variables were computed using linear regression models or nonparametric tests as appropriate. Statistical significance was corrected for multiple comparisons (Bonferroni method). <h3>Results:</h3> In our sample, median age was 15.9 years (interquartile range [IQR] 13.6 – 16.8), 68% (36 patients) were girls and the mean disease duration was 1.8±1.7 years. Cluster analysis identified three cognitive phenotypes: preserved cognition (27 patients [51%]), mild verbal memory/semantic fluency involvement (19 patients [36%]) and severe multidomain involvement (7 patients [13%]). Across groups, there were no significant differences in age, sex and disease duration. Lower EDSS scores were found in patients with preserved cognition (median EDSS 1.0 [IQR 1.0 – 1.0]) than patients with mild verbal memory/semantic fluency involvement (median EDSS 1.5 [IQR 1.0 – 2.0]; p=0.01) and patients with severe multidomain involvement (median EDSS 2.0 [IQR 1.25 – 2.75]; p=0.004). <h3>Conclusions:</h3> Pediatric MS patients present with distinct cognitive phenotypes ranging from preserved cognition to severe multidomain involvement. Cognitive phenotypes are not associated with age, sex and disease duration. Patients with preserved cognition are characterized by low global disability. <b>Disclosure:</b> Damiano Mistri has nothing to disclose. Monica Margoni has received research support from MAGNIMS. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bristol Myers Squibb . Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi Genzyme. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck. Alessandro Meani has nothing to disclose. Carmen Vizzino has nothing to disclose. Dr. Moiola has nothing to disclose. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, Takeda, and Teva Pharmaceutical Industries. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, Takeda, and Teva Pharmaceutical Industries. Dr. Filippi 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 Springer Nature. The institution of Dr. Filippi has received research support from Biogen Idec, Merck-Serono, Novartis, Roche, Teva Pharmaceutical Industries, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, and ARiSLA (Fondazione Italiana di Ricerca per la SLA). Maria Assunta Rocca has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bayer, Biogen, Bristol Myers Squibb, Celgene, Genzyme, Merck Serono, Novartis, Roche, and Teva. The institution of Maria Assunta Rocca has received research support from Italian Ministry of Health, MS Society of Canada and Fondazione Italiana Sclerosi Multipla.

Stepwise functional brain architecture from disease epicenter correlates with atrophy in progressive supranuclear palsy (P11-6.001)

<h3>Objective:</h3> This study applied SFC to test the hypothesis that topological stepwise architecture propagating from the disease epicenter would shape patterns of grey matter (GM) atrophy in a cohort of patients with progressive supranuclear palsy (PSP). <h3>Background:</h3> MRI connectomics is an ideal tool to test the model of network-based spread of pathological protein aggregates in neurodegenerative disorders. Stepwise functional connectivity (SFC) is a graph-theory-based neuroimaging method, which detects whole-brain functional couplings of a selected region of interest, at increasing link-step topological distances. <h3>Design/Methods:</h3> Twenty-eight patients with PSP and 50 healthy controls underwent brain magnetic resonance imaging (MRI) on a 3T scanner, including 3D-T1 weighted and resting-state functional MRI sequences. GM was parcellated into 90 regions using the Automated Anatomical Labeling (AAL) atlas. Correlations between SFC architecture in controls and atrophy patterns in PSP patients were tested. The disease epicenter was identified as the peak of atrophy observed in an independent cohort of 13 cases with <i>post mortem</i> confirmation of PSP pathology, and used as seed region for SFC analysis. <h3>Results:</h3> The disease epicenter was identified in the left midbrain tegmental region. Compared with controls, PSP patients showed prevalent atrophy in the subcortical GM (mostly, in the thalami and caudate nuclei), but also in frontal, parietal and cerebellar cortical regions. For each region of the AAL atlas, a strong correlation was found between average link-step distance from the left midbrain in controls and mean normalized GM volume in PSP patients (r=0.37, p&lt;0.001). <h3>Conclusions:</h3> Our findings demonstrate that the brain architectural topology, as described by SFC propagating from the disease epicenter, shapes the pattern of atrophic changes in PSP, supporting the view of a network-based pathology propagation in this disease and holding the promise to be used to model disease progression in future longitudinal studies. <b>Disclosure:</b> Dr. Spinelli has nothing to disclose. Miss Ghirelli has nothing to disclose. Miss Bottale has nothing to disclose. Silvia Basaia has nothing to disclose. Ms. Cividini has nothing to disclose. Dr. Volonte has nothing to disclose. Mr. Galantucci has nothing to disclose. Giuseppe Magnani has nothing to disclose. Dr. Caso has nothing to disclose. The institution of Elisa Canu has received research support from Italian Ministry of Health . Dr. Castelnovo has nothing to disclose. Paola Caroppo has nothing to disclose. Sara Prioni has nothing to disclose. Miss Villa has nothing to disclose. Dr. Josephs has nothing to disclose. Dr. Whitwell has nothing to disclose. Federica Agosta has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Philips. Federica Agosta has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier INC. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, Takeda, and Teva Pharmaceutical Industries. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, Takeda, and Teva Pharmaceutical Industries. Dr. Filippi 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 Springer Nature. The institution of Dr. Filippi has received research support from Biogen Idec, Merck-Serono, Novartis, Roche, Teva Pharmaceutical Industries, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, and ARiSLA (Fondazione Italiana di Ricerca per la SLA).

Efficacy and Safety Profile of Cladribine Tablets in an Italian Real-Life Cohort of Relapsing-Remitting Multiple Sclerosis Patients: A Monocentric Longitudinal Observational Study (P8-3.015)

<h3>Objective:</h3> To report real-world findings about efficacy and safety of cladribine (CLAD) in relapsing-remitting multiple sclerosis (RRMS), identifying predictors of response. <h3>Background:</h3> CLAD induces a transient lymphocyte depletion followed by immune reconstitution, with improved immune tolerance. Real-world data on CLAD performance and its predictors of response are limited. <h3>Design/Methods:</h3> Monocentric, observational, real-world study on pwMS who started CLAD from April 2018 to November 2021, with a minimum 6 month-follow-up. <h3>Results:</h3> Our population comprised 114 pwMS, 71.9% females, 50% naïves, mean age 33.0 years, median disease duration 3.0 years, median baseline EDSS 2.0, mean 1 and 2 year-baseline ARR 1.3 and 1.2. Median follow-up: 23.8 months. 4.4% and 30.7% patients presented relapses and MRI activity in the first 6 months. When considering data re-baselined towards month 6, 12 relapses were reported. 84% (CI 76–92) and 76% (CI 67–87) patients had no MRI activity at 12 and 24 months, respectively. At month 24, NEDA-3 status was reached by 69% of naïves, and 81% and 55% of switchers from low and high-efficacy treatments, respectively. Eleven patients switched to other treatments. Younger age (HR 0.94, CI: 0.89–0.99, <i>p=0.011</i>), baseline EDSS score ≥ 3.0 (HR 4.29, CI: 1.83–10.05, <i>p=0.0008</i>) and gadolinium-enhancing lesion count ≥ 4 (HR 2.24, CI: 0.95–5.26, <i>p=0.065</i>) were risk factors for loss of NEDA-3. 20.0% of pwMS referred side effects: skin rash, fever/infections, fatigue. Lymphopenia was more likely at months 3 and 15. No grade-4 lymphopenia cases were observed. <h3>Conclusions:</h3> CLAD is more effective when placed early in the treatment algorithm: naïves or switchers from lower efficacy drugs seem to benefit more. Baseline age, disability and gadolinium-enhancing lesions are risk factors for loss of NEDA-3. CLAD was overall well tolerated. Real-world data on larger populations with longer follow-up are needed to confirm our findings. <b>Disclosure:</b> Chiara Zanetta has nothing to disclose. Maria Assunta Rocca has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bayer, Biogen, Bristol Myers Squibb, Celgene, Genzyme, Merck Serono, Novartis, Roche, and Teva. The institution of Maria Assunta Rocca has received research support from Italian Ministry of Health, MS Society of Canada and Fondazione Italiana Sclerosi Multipla. Alessandro Meani has nothing to disclose. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bristol Myers Squibb . Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi Genzyme. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck. Dr. Martinelli has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis, Biogen, Sanofi Genzyme, TEVA and Merck. Dr. Martinelli has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck . Laura Ferrè, 3233 has received intellectual property interests from a discovery or technology relating to health care. Dr. Moiola has nothing to disclose. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, Takeda, and Teva Pharmaceutical Industries. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, Takeda, and Teva Pharmaceutical Industries. Dr. Filippi 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 Springer Nature. The institution of Dr. Filippi has received research support from Biogen Idec, Merck-Serono, Novartis, Roche, Teva Pharmaceutical Industries, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, and ARiSLA (Fondazione Italiana di Ricerca per la SLA).