Stony Brook University
Neurology

Author Of 6 Presentations

Invited Presentations Invited Abstracts

BD02.02 - Presentation 02 (ID 174)

Speakers
Authors
Presentation Number
BD02.02
Presentation Topic
Invited Presentations

Abstract

Abstract

Multiple disease modifying therapies (DMTs) are available for relapsing forms of MS, including active secondary progressive MS (SPMS). Only one DMT is approved for primary progressive MS (PPMS). There is a lack of effective treatments for neurodegeneration injury and progressive MS. Clinical trials remain the fundamental way to establish a treatment benefit.

To date, defining MS by clinical phenotype remains the accepted approach, and we should not abandon this. We need to focus on progressive MS, both active and not active, and document whether therapies can slow neurodegenerative injury. This discussion will make the case for pursuing such trials.

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Clinical Trials Poster Presentation

P0202 - Durable efficacy of cladribine tablets: cumulative relapse incidence over 5 years in CLARITY and CLARITY Extension (ID 960)

Speakers
Presentation Number
P0202
Presentation Topic
Clinical Trials

Abstract

Background

In CLARITY and CLARITY Extension (NCT00213135 and NCT00641537, respectively), treatment with cladribine tablets 10 mg (cumulative dose 3.5 mg/kg over 2 years [CT3.5]) significantly reduced relapse rates in patients with relapsing-remitting multiple sclerosis. Moreover, in the CLARITY Extension study, treatment with cladribine tablets for 2 years followed by treatment with placebo for 2 years produced similar clinical benefits to 2 years of cladribine tablets treatment followed by an additional 2 years of treatment, but with a lower risk of higher grade lymphopenia.

Objectives

To assess, post hoc, the temporal occurrence of relapses up to 5 years after treatment initiation with cladribine tablets.

Methods

Patients enrolled into CLARITY treated with CT3.5, and those subsequently receiving CT3.5 (CC7) or placebo (CP3.5) in CLARITY Extension, were included for analysis. The main endpoint was all qualifying relapses reported in CLARITY or CLARITY Extension plus those that occurred during the variable bridging interval (range: 1 day to 118 weeks). A recurrent event analysis was performed to estimate mean cumulative number of relapses over time using a cumulative mean function estimate.

Results

A total of 433 patients from CLARITY treated with CT3.5 were included in this analysis; of these 284 patients entered CLARITY Extension (CP3.5, n=98; CC7, n=186). Recurrent event analysis for the CT3.5 population showed that annual increase in mean cumulative number of relapses was consistently low from Year 2 to Year 5 (range: 0.10–0.15) and was slightly higher in Year 1 (0.17); the 6-month increase in mean cumulative number of relapses was similar in the first 6 months and the second 6 months (0.08 and 0.09, respectively). There were no differences in mean cumulative number of relapses between the CP3.5 and CC7 groups from Year 2 to Year 5. In recurrent event analysis for the CT3.5 population, the yearly increments of mean cumulative function were constant and low from the second treatment to Year 5, supporting the durable efficacy of cladribine tablets (given no increase in relapses following completion of the two courses of cladribine tablets).

Conclusions

Annual increase in mean cumulative number of relapses occurred at a low annualized rate of 0.10 to 0.17 per year to 5 years, almost 4 years after the last dose of cladribine tablets and therefore consistent with durable efficacy. Results also support the early effect of cladribine tablets on relapses, which is apparent in the first year of treatment.

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Clinical Trials Poster Presentation

P0215 - Long-term efficacy and safety of ponesimod: Results from randomized phase II core and extension studies in relapsing‑remitting multiple sclerosis (ID 470)

Speakers
Presentation Number
P0215
Presentation Topic
Clinical Trials

Abstract

Background

Ponesimod, an orally active, selective sphingosine 1-phosphate receptor-1 (S1P) modulator, showed benefits in clinical and MRI outcomes in a double-blind, placebo controlled, phase 2b Core Study (NCT01006265). Patients rolled-over into an ongoing Extension Study (NCT01093326).

Objectives

Evaluate the long-term efficacy and safety of ponesimod in patients with relapsing-remitting multiple sclerosis (RRMS).

Methods

A total of 435 patients with RRMS received ≥1 dose of ponesimod (10, 20, or 40-mg/day) during the Core and/or Extension Study. The 40 and 10-mg doses were subsequently discontinued during Treatment Period 1 (TP1) and TP2 of the Extension Study. All patients received 10 or 20-mg during TP2, followed by open-label 20-mg in TP3. Key efficacy parameters: annualized relapse rate (ARR), 6-month confirmed disability accumulation (CDA), and MRI outcomes. Safety parameters: frequencies of adverse events (AEs) and serious AEs (SAEs). Results of combined analyses of Core and Extension studies are presented.

Results

As of 31 March 2019, 214 patients were still on ponesimod treatment; median exposure in 20-mg group was 8.02 years; Cumulative exposure across all doses was 2372.47 patients-years. In 20-mg group, ARR (95% CI) for confirmed relapses was 0.154 (0.111‒0.214); 64.1% patients remained free of confirmed relapse; Kaplan-Meier estimate of 6- month CDA at Week 432 was 20.4% (13.7‒29.7); Mean number of T1 gadolinium enhancing lesions per patient per scan was 0.448 (0.305‒0.657); Mean number of new or enlarging T2 lesions per year was 0.718 (0.523‒0.985). In ponesimod-treated patients, the most common treatment-emergent AEs were nasopharyngitis (30%), headache (24%) and upper respiratory tract infection (21%). Most SAEs were reported in a single patient, no SAE was reported at an incidence of >1%.

Conclusions

Long-term treatment with ponesimod 20 mg showed consistently low levels of disease activity across relevant clinical and MRI outcomes in patients with RRMS. No new safety signals were identified.

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Disease Modifying Therapies – Mechanism of Action Poster Presentation

P0308 - Changing patterns of first line and first switch ocrelizumab use in the United States: Analysis of subtype, gender, age, and disability (ID 558)

Speakers
Presentation Number
P0308
Presentation Topic
Disease Modifying Therapies – Mechanism of Action

Abstract

Background

Use of disease-modifying therapies (DMTs) for the treatment of multiple sclerosis (MS) is driven by many factors that are not well understood. In March 2017, ocrelizumab (OCR), an intravenous humanized anti-CD20 monoclonal antibody (mAb), was approved in the United States for the treatment of relapsing-remitting MS (RRMS) and primary progressive MS (PPMS).

Objectives

To examine whether the type of MS patient being treated with OCR first line or as a first switch is changing over time in the United States.

Methods

Cross-sectional MS patient-level data were collected once-yearly from practicing United States neurologists from 2017 to 2020. Contributed chart review data were from MS patients either initiating their first DMT (2017 n=1,033; 2018 n=1,059; 2019 n=1,006) or switching to a new DMT (2018 n=1,035; 2019 n=1,003; 2020 n=1,009) within the prior three months. Analyses focused on new OCR starts (2017 n=70; 2018 n=107; 2019 n=102) and first switches to OCR (2018 n=60; 2019 n=85; 2020 n=90). Relapsing forms of MS (RMS) is defined as clinically isolated syndrome and RRMS.

Results

Overall use of OCR in treatment-naïve MS individuals has increased since 2017, with a decrease in PPMS offset by an increase in RMS. By 2019, OCR was the initial DMT choice in 7% of RMS individuals, while use decreased from 63% in 2017 to 35% of PPMS. Of all new OCR DMT starts evaluated in 2019, RMS made up 58% and PPMS 31%. OCR starts are increasingly female, with 65% of 2019 new start use among female MS patients. This pattern is seen for both RMS and PPMS, although is more marked for PPMS. Mean age of MS patients initiating OCR has decreased by 4.6 years since 2017. OCR use in those aged ≥56 years has fallen to 12% compared to 31% in 2017. Mean Expanded Disability Status Scale (EDSS) score decreased in the PPMS cohort who initiate OCR therapy, but increased in the RMS cohort.

Among MS individuals who made a first switch to OCR in 2018-2020, more switches were among RMS patients compared to PPMS. Switches to OCR are now most likely from first-line glatiramer acetate (GA; 39%), followed by dimethyl fumarate (18%). Switches from interferon beta have decreased from 33% to 17%. In PPMS, the second most common switch is from another mAb therapy to OCR (accounting for 24% of 2020 switches up from 11% of 2018 switches). First switches to OCR are increasingly among female MS patients (2020: 64% vs. 2018: 50%), especially among PPMS patients. Mean age and EDSS score have not changed significantly over time when assessed by total, MS subtype, or gender.

Conclusions

OCR initiation as a first-line agent is on the rise, driven by increased use among RMS patients, and is being used in younger MS individuals. First-line OCR use in females with PPMS has increased over time. Initial switches to OCR are increasingly coming from GA. The usage pattern of OCR in the United States is evolving and changing over time.

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Disease Modifying Therapies – Risk Management Poster Presentation

P0367 - Online Medical Simulation Identifies Rationales for the Use and Avoidance of DMTs for Highly Active MS Among Neurologists (ID 1141)

Speakers
Presentation Number
P0367
Presentation Topic
Disease Modifying Therapies – Risk Management

Abstract

Background

Despite the availability of over a dozen different disease-modifying therapies (DMTs) for the long-term management of multiple sclerosis (MS), evidence shows that clinicians have difficulty personalizing the selection of these therapies. To help address this issue it is important to assess the clinical decision-making process of clinicians who manage MS. .

Objectives

A study utilizing a proprietary online medical simulation platform assessed the specific reasons why neurologists chose or avoided DMTs in patients with highly active MS.

Methods

A cohort of US-based neurologists who participated in a simulation-based CME intervention were evaluated. The simulation consisted of two cases presented in a platform that allowed physician learners to choose from lab tests and assessment scales as well as the free form identification of a specific diagnosis and appropriate therapeutic treatment. Both of the cases involved a patient with highly active MS and who is a candidate for higher efficacy DMTs. Clinical decisions made by the participants regarding assessment, diagnosis, and treatment are captured. After a physician learner identifies a specific DMT, he or she is then prompted to select an appropriate rationale for why a DMT was chosen. A rationale was also asked if a DMT was chosen which was not an immune reconstitution therapy. The data being reported focus only on the rationale portion of the simulation. Data were collected between June 6, 2019 and September 25, 2019.

Results

112 neurologists completed the first case simulation and 80 neurologists completed the second case simulation. The first case was a patient diagnosed with MS 8 months ago and initially prescribed dimethyl fumarate, but is experiencing a debilitating relapse with new lesions on MRI. Among the monoclonal antibodies chosen by the learners, perceived efficacy was the most frequently chosen rationale. Fingolimod and siponimod were chosen due to the oral route of administration. In learners who did not choose alemtuzumab or cladribine, insurance coverage and adverse events were the reasons given for avoiding these therapies. In the second case, the patient was diagnosed with MS 22 months ago, was on several prior DMTs, and most recently experienced a relapse with new MRI lesions while receiving fingolimod. Learners who chose to treat this patient with cladribine and natalizumab did so because of its perceived efficacy. The most frequent reason for choosing alemtuzumab was because it results in immune reconstitution and those who chose ocrelizumab did so because of positive clinical trial data. In learners who did not choose alemtuzumab or cladribine, insurance coverage and adverse events were the most common reasons.

Conclusions

This study demonstrated that neurologists choose DMTs for different reasons depending on the case. Additional programming should continue to identify rationales for the selection of DMTs in clinically representative cases of MS.

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Invited Presentations Invited Abstracts

TC04.02 - Presentation 02 (ID 598)

Speakers
Authors
Presentation Number
TC04.02
Presentation Topic
Invited Presentations

Abstract

Abstract

Abstract:
Accurate Diagnosis of MS: Getting it Right

This Teaching Course focuses on three 30-minute presentations. Each will begin with a brief case, and end with a brief Q&A.

Dr. PK Coyle will discuss diagnostic issues and guidelines, including the rationale for early diagnosis, optimal use of the 2017 revised McDonald criteria, and general misdiagnosis principles.

Dr. Wallace Brownlee will cover differential diagnosis, including the major alternative diagnoses for relapsing or progressive presentations and key diagnostic clues.

Dr. Georgina Arrambide will present pearls on ancillary diagnostic testing, including updates on MRI standardization and novel techniques, use of CSF, optical coherence tomography, and other novel approaches to diagnosis.

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Presenter Of 2 Presentations

Invited Presentations Invited Abstracts

BD02.02 - Presentation 02 (ID 174)

Speakers
Authors
Presentation Number
BD02.02
Presentation Topic
Invited Presentations

Abstract

Abstract

Multiple disease modifying therapies (DMTs) are available for relapsing forms of MS, including active secondary progressive MS (SPMS). Only one DMT is approved for primary progressive MS (PPMS). There is a lack of effective treatments for neurodegeneration injury and progressive MS. Clinical trials remain the fundamental way to establish a treatment benefit.

To date, defining MS by clinical phenotype remains the accepted approach, and we should not abandon this. We need to focus on progressive MS, both active and not active, and document whether therapies can slow neurodegenerative injury. This discussion will make the case for pursuing such trials.

Collapse
Invited Presentations Invited Abstracts

TC04.02 - Presentation 02 (ID 598)

Speakers
Authors
Presentation Number
TC04.02
Presentation Topic
Invited Presentations

Abstract

Abstract

Abstract:
Accurate Diagnosis of MS: Getting it Right

This Teaching Course focuses on three 30-minute presentations. Each will begin with a brief case, and end with a brief Q&A.

Dr. PK Coyle will discuss diagnostic issues and guidelines, including the rationale for early diagnosis, optimal use of the 2017 revised McDonald criteria, and general misdiagnosis principles.

Dr. Wallace Brownlee will cover differential diagnosis, including the major alternative diagnoses for relapsing or progressive presentations and key diagnostic clues.

Dr. Georgina Arrambide will present pearls on ancillary diagnostic testing, including updates on MRI standardization and novel techniques, use of CSF, optical coherence tomography, and other novel approaches to diagnosis.

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Moderator Of 1 Session

Teaching Course Fri, Sep 11, 2020
Session Type
Teaching Course
Date
Fri, Sep 11, 2020

Invited Speaker Of 2 Presentations

Invited Presentations Invited Abstracts

BD02.02 - Presentation 02 (ID 174)

Speakers
Authors
Presentation Number
BD02.02
Presentation Topic
Invited Presentations

Abstract

Abstract

Multiple disease modifying therapies (DMTs) are available for relapsing forms of MS, including active secondary progressive MS (SPMS). Only one DMT is approved for primary progressive MS (PPMS). There is a lack of effective treatments for neurodegeneration injury and progressive MS. Clinical trials remain the fundamental way to establish a treatment benefit.

To date, defining MS by clinical phenotype remains the accepted approach, and we should not abandon this. We need to focus on progressive MS, both active and not active, and document whether therapies can slow neurodegenerative injury. This discussion will make the case for pursuing such trials.

Collapse
Invited Presentations Invited Abstracts

TC04.02 - Presentation 02 (ID 598)

Speakers
Authors
Presentation Number
TC04.02
Presentation Topic
Invited Presentations

Abstract

Abstract

Abstract:
Accurate Diagnosis of MS: Getting it Right

This Teaching Course focuses on three 30-minute presentations. Each will begin with a brief case, and end with a brief Q&A.

Dr. PK Coyle will discuss diagnostic issues and guidelines, including the rationale for early diagnosis, optimal use of the 2017 revised McDonald criteria, and general misdiagnosis principles.

Dr. Wallace Brownlee will cover differential diagnosis, including the major alternative diagnoses for relapsing or progressive presentations and key diagnostic clues.

Dr. Georgina Arrambide will present pearls on ancillary diagnostic testing, including updates on MRI standardization and novel techniques, use of CSF, optical coherence tomography, and other novel approaches to diagnosis.

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