Center for Neurology

Moderator Of 1 Session

Free Communications Sun, Sep 13, 2020
Moderators
Session Type
Free Communications
Date
Sun, Sep 13, 2020
Time (ET)
13:00 - 14:15

Author Of 5 Presentations

COVID-19 Late Breaking Abstracts

LB1218 - Impact of COVID-19 on MS patients’ access to care and neurologists’ treatment practices worldwide: results from the ECTRIMS survey (ID 2086)

Speakers
Presentation Number
LB1218
Presentation Topic
COVID-19

Abstract

Background

Restrictions imposed by the National and local authorities to mitigate the spread of Coronavirus disease-19 (COVID-19) posed unique challenges in the access to care and management of people with multiple sclerosis (PwMS).

Objectives

To collect data about the impact of the COVID-19 emergency on access to care for PwMS and analyze influence on treatment practices of MS neurologists worldwide.

Methods

Between March and July 2020 the European Committee for Treatment and Research in MS (ECTRIMS) promoted an online survey among Council members and MS specialists worldwide, covering five major areas: general information; MS patient access to care; management of relapses and visits; use of disease modifying therapy (DMT); experience with COVID-19 MS patients.

Results

Three-hundred-sixty neurologists (46% females, median age 48 years) from 52 countries (Europe 68%; Central/South America 17%; North America 10%, others 5%) completed the survey. Seventy-five percent worked within a specialized MS centre, 42% followed > 1000 patients. Ninety-eight percent of respondents reported COVID-19 pandemic had a negative impact on patients’ care. Routine MS clinical activities were suspended in 63% of cases and only urgent visits were guaranteed. Telemedicine services (mainly calls, video-calls, messaging) were provided by 90% of respondents: only in 20% of cases telemedicine was already in use in the practice. Forty-five percent revealed changes in relapse treatment: dosage and/or duration reduction 30%; treatment offered only for severe relapses 36%; treatment delivered at home 28%. As for DMT, 98% of respondents felt no modification was needed for interferons and glatiramer; 48-60% deemed no change was needed for dimethyl fumarate, teriflunomide, fingolimod and siponimod, while nearly 25% considered switching/suspending these agents based on lymphopenia. On the other hand, for natalizumab 31% applied an extended-dose regimen, for cladribine and alemtuzumab 42-52% considered postponing treatment in any case as the best choice. For anti-CD20 monoclonal antibodies, postponing treatment in any case (32%) or based on the patient immunophenotype (25%) were the preferred options. Sixty-one percent of respondents had at least one patient affected by COVID-19, 27% had at least one patient with severe infection; 70% of severe cases were on DMT. Finally, 11% of respondents reported at least one COVID-19 related death and 36% of fatal cases were on DMT.

Conclusions

While analysis of geographic differences is ongoing, the survey highlighted that COVID-19 pandemic is having a major impact on MS care worldwide. Telemedicine has a great potential to mitigate issues and needs to be potentiated/implemented de novo at most centres. As for DMT, major changes regarded cladribine, alemtuzumab and anti-CD20. Collecting standardized, reliable data on the potential impact of DMT on COVID-19 in PwMS is urgently needed to inform appropriate treatment decisions.

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Clinical Outcome Measures Poster Presentation

P0128 - Outcomes in Alemtuzumab-Treated Patients With Thyroid Adverse Events: 6-Year Pooled CARE-MS Data (ID 736)

Abstract

Background

Over 6 years in the CARE-MS core and extension trials (NCT00530348; NCT00548405; NCT00930553), alemtuzumab improved outcomes in RRMS patients, but many experienced thyroid adverse events (AEs).

Objectives

To characterize thyroid AEs over 6 years in alemtuzumab-treated patients from the CARE-MS core and extension trials.

Methods

Patients received 2 alemtuzumab courses, with as-needed additional alemtuzumab ≥12 months after the most recent course. An expert panel of 3 independent endocrinologists reviewed all reported cases of thyroid-related laboratory abnormalities and AEs to assess diagnosis, start date, and outcome through a consensus approach. Cases for which consensus was not reached, or those that were preexisting or occurred after Y6 were excluded.

Results

Over 6 years, 378/811 (47%) alemtuzumab-treated patients had a thyroid AE or laboratory abnormality (342 [42%] with thyroid AE; 44 serious AEs). After panel review, 292 cases had a consensus diagnosis as a thyroid AE, no consensus diagnosis could be reached in 60 cases, 2 cases were deemed pre-existing, and 24 occurred after Y6. Cases with a consensus diagnosis were adjudicated to Graves’ disease (40%), Hashimoto’s disease (17%), transient thyroiditis (8%), Graves’ disease switching to hypothyroidism (6%), Hashimoto’s disease switching to hyperthyroidism (3%), or uncertain (27%). Oral thyroid medications were given to 245/292 (84%) patients, primarily levothyroxine/levothyroxine sodium (n=187; 64%) or thiamazole (n=126; 43%); 32/292 (11%) patients underwent thyroidectomy and 26/292 (9%) underwent radioiodine therapy. Within 2 years of the last alemtuzumab course, 83% of thyroid AEs appeared (>97% were detected within 4 years). Patients with vs without thyroid AEs received similar numbers of alemtuzumab courses (2 courses: 62% vs 60% of patients; 3 courses: 24% in each group). From baseline to Y6, MS disease outcomes were similar in patients with vs without thyroid AEs (annualized relapse rate: 0.20 vs 0.21; mean EDSS score change: −0.04 vs +0.08; proportion with stable/improved EDSS scores: 81% vs 80%; proportions MRI disease activity-free: 60%-78% per year vs 60%-76% per year; and median cumulative brain volume loss: −1.11% vs −1.27%). Outcomes as of last follow-up were recovered (53%), ongoing (46%), and unknown (0.3%).

Conclusions

Graves’ disease was the most common thyroid AE. Most thyroid AEs were treated with oral medications. No differences in 6-year MS disease outcomes were seen when comparing patients with or without thyroid AEs.

STUDY SUPPORT: Sanofi and Bayer Healthcare Pharmaceuticals.

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Clinical Trials Poster Presentation

P0217 - Long-term safety and efficacy of ozanimod in relapsing multiple sclerosis in DAYBREAK: an open-label extension study of ozanimod phase 1−3 trials (ID 991)

Abstract

Background

Ozanimod, an oral sphingosine 1-phosphate receptor 1 and 5 modulator, is approved in the US and EU for the treatment of relapsing forms of multiple sclerosis (RMS).

Objectives

To characterize the long-term safety and efficacy of ozanimod in participants with RMS in an ongoing open-label extension (OLE) trial.

Methods

Participants with RMS who completed a phase 1, 2, or 3 ozanimod clinical trial were eligible to enroll in DAYBREAK (NCT02576717), where they received ozanimod 0.92 mg/d (equivalent to ozanimod HCl 1 mg). The primary objective was to evaluate safety in the overall population; treatment-emergent adverse events (TEAE) were monitored. Efficacy was evaluated with annualized relapse rate (ARR), calculated via negative binomial regression and pooled for all parent-trial treatment groups. Number of new/enlarging T2 and gadolinium-enhancing (GdE) MRI brain lesions were reported for the subset of participants who entered the OLE from an active-controlled phase 3 trial.

Results

In total, 2639 participants completed the parent trials; this interim analysis (data cut 20 December 2019) included 2494 participants with mean (range) ozanimod exposure of 35.4 (0.03–50.2) months in the OLE. Adjusted ARR in the OLE was 0.112 (95% confidence interval, 0.093‒0.135). At months 24 and 36, 79% and 75% of participants, respectively, were relapse free in the OLE. Three- and 6-month confirmed disability progression was observed in 10.8% and 8.6% of participants in the OLE, respectively. Mean number of new/enlarging T2 lesions per scan at 24 months was similar, regardless of parent-trial treatment group (range, 1.57–1.90), as were mean number of GdE lesions at month 24 (range, 0.2 ‒0.4). In the OLE, 2039 participants (81.8%) had any TEAE, 236 (9.5%) had a serious TEAE (SAE), and 56 (2.2%) discontinued due to a TEAE. Similar rates of TEAEs and SAEs occurred when assessed by parent-trial treatment group. The most common TEAEs were nasopharyngitis (17.9%), headache (14%), upper respiratory tract infection (9.9%), and lymphopenia (9.6%). TEAEs were generally similar to parent trial observations. There were no serious opportunistic infections. Exposure-adjusted incidence rates of TEAEs and SAEs have decreased over time.

Conclusions

In DAYBREAK, ozanimod was associated with low ARR and low new/enlarging T2 and GdE lesion counts over time. Most participants were relapse free and did not experience disability progression. Ozanimod was generally well tolerated and no new safety concerns emerged with long-term use.

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Clinical Trials Poster Presentation

P0236 - Serum immunoglobulin levels and infection risk in the Phase 3 trials of ofatumumab in relapsing multiple sclerosis (ID 1566)

Abstract

Background

Ofatumumab, a fully human anti-CD20 monoclonal antibody, demonstrated superior efficacy vs teriflunomide with a favorable safety profile in relapsing MS (RMS) patients in the Phase 3 ASCLEPIOS I/II trials. Reductions in serum immunoglobulin (Ig) M and IgG levels are associated with anti-CD20 therapies.

Objectives

To assess the effect of ofatumumab on serum Ig levels and evaluate potential association between a decrease in IgM/IgG levels and risk of infections.

Methods

Patients were randomized to receive subcutaneous ofatumumab 20 mg (initial doses: Days 1, 7, and 14; subsequent doses: every 4 weeks from Week (W) 4 onwards) or oral teriflunomide 14 mg once-daily for up to 30 months (m, mean follow-up duration: 18m). Serum IgM/IgG levels were monitored at baseline (BL), W4, W12, and every 12 weeks thereafter (ofatumumab, n=946; teriflunomide, n=936). Proportion of patients with IgM/IgG levels below the lower limit of normal (<LLN [g/L]: IgM, 0.4; IgG, 7.0), and association of IgM/IgG levels with incidence of infections that occurred up to 1m prior and 1m after any decrease in IgM/IgG levels (<LLN vs ≥LLN) were analyzed. Infections in conjunction with IgM/IgG <LLN and lymphopenia and/or neutropenia on the same visit were also analyzed.

Results

Mean IgM/IgG levels were well within reference ranges over time. Over all post-BL visits, a higher proportion of patients on ofatumumab had IgM<LLN (17.7% vs 6.6%), whilst a lower proportion had IgG<LLN (14.2% vs 22.9%) vs patients on teriflunomide. At W96, a similar trend was observed (IgM<LLN: 11.1% vs 1.9%; IgG<LLN: 2.7% vs 6.0%). Proportion of patients on ofatumumab who experienced ≥1 infection within 1m prior and until 1m after IgM<LLN was 31.1% (52/167; 2 serious) vs 51.5% (400/777) with IgM≥LLN (18 serious). Similarly, 27.6% (37/134) reported infections during a drop in IgG<LLN (3 serious) vs 50.6% (410/810) with IgG≥LLN (21 serious). The most common infection was nasopharyngitis. Overall, 1/11 patients with concurrent IgM<LLN and lymphopenia and/or neutropenia, and 7/20 patients with concurrent IgG<LLN and lymphopenia and/or neutropenia reported infections; none were serious.

Conclusions

Reduction in serum IgM levels was observed over time, but for the majority of patients, Ig levels remained above the lower limit of normal. No decrease in IgG levels was reported within the observation period (mean follow-up: 18m). There was no apparent association between decreased Ig levels and infections in conjunction with lymphopenia and/or neutropenia in ofatumumab-treated RMS patients.

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Patient-Reported Outcomes and Quality of Life Poster Presentation

P1066 - Treatment satisfaction in patients with highly-active relapsing multiple sclerosis treated with cladribine tablets: CLARIFY-MS study interim analysis (ID 968)

Speakers
Presentation Number
P1066
Presentation Topic
Patient-Reported Outcomes and Quality of Life

Abstract

Background

Multiple sclerosis (MS), a chronic disabling disease requiring long-term treatment and regular monitoring, is associated with negative effects on health-related quality of life (HRQoL). CLARIFY-MS (NCT03369665) aims to assess the impact of cladribine tablets (CT) 10 mg (3.5 mg/kg cumulative dose over 2 years; CT3.5) on HRQoL and treatment satisfaction in patients with highly-active relapsing MS (RMS).

Objectives

To present an interim analysis of CLARIFY-MS at 6 months after initiating treatment with CT, assessing treatment satisfaction through the Treatment Satisfaction Questionnaire for Medication (TSQM) v1.4 and safety through the collection of safety assessments in highly-active RMS patients.

Methods

CLARIFY-MS is an ongoing phase IV, open label, single arm, multicenter, 2-year study. Patients with RMS received CT3.5, with 2 weeks of active treatment per course (week 1 and 5 of each year). TSQM v1.4 was used to assess patient-reported treatment satisfaction (a score of 100 is the best possible rating). The TSQM measures 14 items across four domains: effectiveness (three items), side effects (five items), convenience (three items), and global satisfaction (three items).Treatment-emergent adverse events (TEAEs), serious adverse events (AEs), and lymphocyte counts were recorded.

Results

Treatment satisfaction: Of 554 patients screened, 482 received CT. The age and Expanded Disability Status Scale adjusted global treatment satisfaction score (95% confidence interval) at Month 6 was 70.0 (66.6–73.5). Treatment-experienced patients (prior treatment with disease-modifying drugs [DMDs]) reported similar treatment satisfaction scores to DMD-naïve patients (70.2 vs 68.7). At Month 6, >75% of patients rated the TSQM side effects score with 100. The mean side effects score was 91.9, mean convenience 86.6. Safety: 275 patients (57.1%) experienced ≥1 TEAE after drug initiation, most commonly headache and lymphopenia. Most post-baseline lymphopenias were of grade 1-2; 33 patients (6.8%) experienced grade 3 lymphopenia and no grade 4 lymphopenia was observed.

Conclusions

This interim analysis of CLARIFY-MS found that at 6 months, patients were generally satisfied with CT treatment. The convenience of CT treatment and side effect profile were especially important to patients. Safety results at 6 months post-treatment are consistent with the known safety profile, with no new emerging safety signal; most lymphopenias were grade 1-2.

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Presenter Of 1 Presentation

Clinical Trials Poster Presentation

P0217 - Long-term safety and efficacy of ozanimod in relapsing multiple sclerosis in DAYBREAK: an open-label extension study of ozanimod phase 1−3 trials (ID 991)

Abstract

Background

Ozanimod, an oral sphingosine 1-phosphate receptor 1 and 5 modulator, is approved in the US and EU for the treatment of relapsing forms of multiple sclerosis (RMS).

Objectives

To characterize the long-term safety and efficacy of ozanimod in participants with RMS in an ongoing open-label extension (OLE) trial.

Methods

Participants with RMS who completed a phase 1, 2, or 3 ozanimod clinical trial were eligible to enroll in DAYBREAK (NCT02576717), where they received ozanimod 0.92 mg/d (equivalent to ozanimod HCl 1 mg). The primary objective was to evaluate safety in the overall population; treatment-emergent adverse events (TEAE) were monitored. Efficacy was evaluated with annualized relapse rate (ARR), calculated via negative binomial regression and pooled for all parent-trial treatment groups. Number of new/enlarging T2 and gadolinium-enhancing (GdE) MRI brain lesions were reported for the subset of participants who entered the OLE from an active-controlled phase 3 trial.

Results

In total, 2639 participants completed the parent trials; this interim analysis (data cut 20 December 2019) included 2494 participants with mean (range) ozanimod exposure of 35.4 (0.03–50.2) months in the OLE. Adjusted ARR in the OLE was 0.112 (95% confidence interval, 0.093‒0.135). At months 24 and 36, 79% and 75% of participants, respectively, were relapse free in the OLE. Three- and 6-month confirmed disability progression was observed in 10.8% and 8.6% of participants in the OLE, respectively. Mean number of new/enlarging T2 lesions per scan at 24 months was similar, regardless of parent-trial treatment group (range, 1.57–1.90), as were mean number of GdE lesions at month 24 (range, 0.2 ‒0.4). In the OLE, 2039 participants (81.8%) had any TEAE, 236 (9.5%) had a serious TEAE (SAE), and 56 (2.2%) discontinued due to a TEAE. Similar rates of TEAEs and SAEs occurred when assessed by parent-trial treatment group. The most common TEAEs were nasopharyngitis (17.9%), headache (14%), upper respiratory tract infection (9.9%), and lymphopenia (9.6%). TEAEs were generally similar to parent trial observations. There were no serious opportunistic infections. Exposure-adjusted incidence rates of TEAEs and SAEs have decreased over time.

Conclusions

In DAYBREAK, ozanimod was associated with low ARR and low new/enlarging T2 and GdE lesion counts over time. Most participants were relapse free and did not experience disability progression. Ozanimod was generally well tolerated and no new safety concerns emerged with long-term use.

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