Advanced Neurosciences Institute

Author Of 4 Presentations

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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Prognostic Factors Poster Presentation

P0475 - Multiple sclerosis (MS) features are related to headache frequency in users of MS Care ConnectTM, a self-efficacy digital application (ID 1247)

Speakers
Presentation Number
P0475
Presentation Topic
Prognostic Factors

Abstract

Background

Migraine headache presents simultaneously with early symptoms in most patients with MS, showing association with MS prevalence and incidence, but the pathological significance of headache remains unclear. Self-reporting instruments offer an opportunity to study this relationship.

Objectives

Cross-sectional study of self-reported headache frequency, MS disability, severity, and disease-modifying therapy (DMT) retrospectively using a de‑identified, archival, database from MS Care ConnectTM, a digital application (InterPRO Bioscience).

Methods

Patient survey responses were transformed into number of headache days per month (HD). A generalized linear mixed-effects (GLMM) model was performed to test the association of HD with: sex, age, weight, disease modifying therapy class, patient self-reported history of MS, MS phenotype, DMT, and either Patient-Derived Disability Score (PDDS) or Patient-Derived MS Severity Score (P‑MSSS). Additional post hoc comparisons further tested associations among significant variables.

Results

253 participants self-reported headache (79% CIS/RRMS, 10% PPMS/SPMS, others “unsure”; mean 45.4 y+11.4 SD, median 45.4 y). Of the 219 suffering >1 HD, 78.7% were female and used mainly highly effective IV and oral MS DMTs with a mean 9.0 HD (median 3). Responders self-reported PDDS (mean 2.2+ 2.0 SD) and yearly relapses mean 0.32 ± 0.6 with a calculated, P‑MSSS decile mean 3.67+2.54. No correlations were detected between HD and PDDS or P-MSSS. A small PPMS/SPMS cohort demonstrated higher median PDDS in the high HD group. Daily headache had highest median PDDS and P-MSSS in RRMS phenotype.

A Poisson GLMM revealed significantly lower HD for males, older subjects, and RRMS subjects over females, younger subjects, and progressive MS subjects, respectively. No interaction occurred among these three variables (age, gender, and MS phenotype). However, a skewed frequency distribution of DMT use by males (more likely to be treated) was associated with fewer HD than females; this skewing did not extend to DMT type. Progressive MS patients were less likely to be on any DMT despite having high HD. The model found non-significant contributions of family history of MS, DMT, P-MSSS and weight. When stratifying PDDS and age and comparing high and low HD groups, younger people (<45y) with high HD have lower PDDS than peers with low HD. In contrast, older people (45+y) have more HD with higher PDDS as compared to similarly aged peers with low HD, although this comparison did not reach significance.

Conclusions

A self-efficacy digital tool presented opportunities to study the interaction of migraine and MS. We significantly found that older, CIS/RRMS, or male subjects have fewer HD than younger, PPMS/SPMS, or female subjects, respectively. Age, MS phenotype, and gender predict HD in our best models and must be controlled in future studies; a relationship to PDDS and P-MSSS requires further investigation in a larger cohort.

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Imaging Poster Presentation

P0577 - Feasibility of thalamic atrophy measurement in clinical routine using artificial intelligence: Results from multi-center study in RRMS patients (ID 1058)

Abstract

Background

The thalamus is a key gray matter structure, and a sensitive marker of neurodegeneration in multiple sclerosis (MS). Previous reports have indicated that thalamic volumetry on clinical-quality T2-FLAIR images alone is fast and reliable, using artificial intelligence (AI).

Objectives

To investigate the feasibility of thalamic atrophy measurement using AI in patients with MS, in a large multi-center, clinical routine study.

Methods

DeepGRAI (Deep Gray Rating via Artificial Intelligence) is a multi-center (31 USA sites), longitudinal, observational, real-word, registry study that will enroll 1,000 relapsing-remitting MS patients. Brain MRI exams previously acquired at baseline and at follow-up on 1.5T or 3T scanners with no prior standardization are used, in order to resemble real-world situation. Thalamic volume measurement is performed at baseline and follow-up on T2-FLAIR by DeepGRAI tool and on 3D T1-weighted image (WI) and 2D T1-WI by using FIRST software.

Results

In this pre-planned interim analysis, 515 RRMS patients were followed for an average of 2.7 years. There were 487 (94.6%) T2-FLAIR, 342 (66.4%) 2D T1-WI and 176 (34.2%) 3D T1-WI longitudinal pair of MRI exams available for analyses. Estimation of thalamic volume by DeepGRAI on T2-FLAIR correlated significantly with FIRST on 3D-T1-WI (r=0.733 and r=0.816, p<0.001) and with FIRST on 2D-T1-WI (r=0.555 and r=0.704, p<0.001) at baseline and at follow-up. The correlation between thalamic volume estimated by FIRST on 3D T1-WI and 2D T1-WI was r=0.642 and r=0.679, p<0.001, respectively. The thalamic volume % change over the follow-up was similar between DeepGRAI (-0.75) and 3D T1-WI (-0.82), but somewhat higher for 2D T1-WI (-0.92). Similar relationship was found between the Expanded Disability Status Scale (EDSS) and thalamic volume by DeepGRAI on T2-FLAIR and by FIRST on 3D T1-WI at baseline (r=-0.214, p=0.01 and r=-0.287, p=0.001) and at follow-up (r=-0.298, p=0.001 and r=-0.291, p=0.001).

Conclusions

DeepGRAI provides feasible thalamic volume measurement on multi-center clinical-quality T2-FLAIR images. The relationship between thalamic atrophy and physical disability is similar using DeepGRAI T2-FLAIR and standard high-resolution research approaches. This indicates potential for real-world thalamic volume monitoring, as well as quantification on legacy datasets without research-quality MRI.

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Patient-Reported Outcomes and Quality of Life Poster Presentation

P1047 - Quality of life (QoL) in treatment-refractory, disabled, multiple sclerosis (MS) during long-term repeated, alemtuzumab (ALE) as assessed by SF-36 (ID 1939)

Speakers
Presentation Number
P1047
Presentation Topic
Patient-Reported Outcomes and Quality of Life

Abstract

Background

Alemtuzumab (ALE) achieves effective protection against disability progression and often improvement in patients with severe multiple sclerosis (MS). The SF-36 health survey is a validated quality-of-life (QoL) outcome with multiple subscales, and has shown differences in low disability MS and short duration of disease in ALE trials..

Objectives

Using longitudinal linear multivariate models, assess changes in QoL in groups switching from other therapies to ALE, or undergoing additional therapy with ALE.

Methods

We prospectively measured changes in QoL with open-label ALE treatment using SF-36 in two arms: ALE-experienced (ALE-X) and ALE-naïve (ALE-N) cohorts with relapsing-remitting MS and secondary progressive MS with relapse, expanded disability status scale (EDSS)<7.0. ALE was given per standard protocols. 60 subjects were recruited and 55 completed the entire intent-to-treat prospective study. The SF-36 questionnaire was completed annually. Mean physical and emotional scores (PS, ES) were calculated from the respective subcategories of the SF-36. Longitudinal linear mixed models were used to test for an association between scores and the primary predictors of either total number of ALE treatments or study arm, with age, sex, EDSS, MS phenotype, and age at MS symptom onset as covariates. Study month was used as the random effect in the models.

Results

Differences of PS and ES between baseline and end of study were not significant, likely a preservation of QoL. Regarding absolute scores, MS phenotype was not associated with scores in any model tested. Total number of ALE treatments had no impact on PS, but covariates age and EDSS were significantly associated with PS. As EDSS increases, PS and ES are lower/worse without an effect of sex. Unexpectedly, PS were subtly but significantly with increasing age at ALE treatment and decreasing EDSS (older patients report higherincreased PS); more dramatic differences were seen for ES. ALE-X patients showed marginal significantly higher PS over ALE-N, possibly related to long-term therapy. ALE-X patients reported a significantly higher ES score than their ALE-N peers over the treatment course. ES also significantly increased with increasing ALE treatments (about 2% for each additional ALE treatment). Covariates of age at MS onset, sex, and EDSS were significantly associated with ES. Lower age at onset, females, and higher EDSS were associated with lower ES.

Conclusions

Both experienced and naïve ALE groups have relatively stable long-term QoL measures. As expected, QoL is negatively associated with EDSS. Older patients perceive greater physical health in our cohorts. Shorter disease duration, lower EDSS, males, and receiving greater ALE courses report better emotional health than those with longer disease duration, higher EDSS, females, or patients with fewer treatments, respectively. Greater QoL in experienced patients may reflect long-term benefit and treatment response.

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