ACTRIMS Conference Express--Interpretation of the latest research on multiple sclerosis

From February 24th to 26th, 2022, the 7th annual academic meeting of the American Council for the Treatment and Research of Multiple Sclerosis (ACTRIMS) was held in Florida.
The latest research in multiple sclerosis (MS) is presented and reported
.

Real-world cross-sectional study: Increased EDSS score is significantly associated with increased economic burden in Chinese MS patients MS is a chronic, disabling neurological disease with clinical manifestations of multiple symptoms, including fatigue, depression, bowel/bladder function Impairment, mobility, and cognitive dysfunction that lead to limited physical activity, reduced work productivity, and increased utilization of healthcare resources in people with MS, among which cognitive impairment is a common and highly disabling disease symptom1 -3
.

Although global estimates suggest a high economic burden for MS patients in China, understanding of MS is still in its infancy due to a lack of detailed local data on clinical unmet need and healthcare utilization.
To describe stratification by EDSS score in China of MS-related direct and indirect costs, a real-world cross-sectional survey study of neurologists and rehabilitation specialists and their MS patients in China from the Adelphi MS disease-specific program (online survey of Chinese neurologists and rehabilitation specialists and their MS patients, June-September 2021).
The data were analyzed and the findings were presented at this conference
.

The study analyzed data from 679 patients with MS.
Generalized linear model (GLM) analysis showed that direct medical costs (+10.
7%, p<0.
001), direct non-medical costs (+25.
4%, p<0.
001) and indirect Increased costs (+38.
8%, p < 0.
001) were significantly associated with increases in continuous EDSS scores, suggesting that interventions that delay or prevent disability progression in MS patients can save downstream costs and reduce social burdens 1
.

Figure 1.
Increased EDSS score is significantly associated with increased economic burden in MS patients.
Chronic lesion demyelination may lead to cognitive impairment in MS patients Cognitive impairment is very common in MS, affecting approximately 40%-70% of patients, and occurs in the early stages of the disease Clinically isolated syndrome (CIS) and radiologically isolated syndrome (RIS) stages already exist, severely impacting patients' quality of life and employment status 3,4
.

Decreased information processing speed is a hallmark cognitive deficit in MS, and the Symbolic Digit Pattern Test (SDMT) is very reliable and sensitive in assessing information processing speed due to its predictive validity, high sensitivity and specificity, ease of administration, and patient friendliness , is often incorporated into clinical practice to help identify MS patients at greatest risk for cognitive impairment, poor prognosis, and disability progression
.

The mechanisms of cognitive decline are still poorly understood, and chronic demyelination within lesions may contribute to this disability
.

At this meeting, a study of 164 patients with MS was performed with fast-acquisition T2prep (FAST-T2) using helical trajectory for myelin water fraction (MWF) analysis, and SDMT was used to assess information processing speed to quantify the rate of change in each MS patient cohort.
The association between lesion-based distribution of myelin damage and cognitive function in 10 patients 7
.

A total of 3588 lesions were found in 164 MS patients.
The mean age of the patients was 43.
3 (±10.
4) years, the mean disease duration was 10.
0 (±7.
4) years, the mean SDMT score was 54.
7 (±14.
6), and the median MWF value per lesion was 0.
079
.

At the patient level, there were two peaks in the distribution of lesions for each patient, indicating that a patient had either more low-MWF lesions and fewer high-MWF lesions, or vice versa
.

Patients with lower SDMT scores had more low-MWF lesions, whereas patients with higher SDMT scores had more high-MWF lesions
.

Regression analysis showed that age (p = 0.
007), sex-male (p = 0.
051), and number of lesions with MWF below cohort Q1 (first quartile) (p = 0.
002) were associated with cognitive impairment, with The number of lesions with low myelin content increased and the SDMT score decreased
.

These results suggest that chronic focal demyelination may contribute to cognitive impairment in MS patients 7
.

Figure 2.
As the number of lesions with low myelin content increases, SDMT scores decrease.
Remote SDMT is an effective and feasible form of management for clinical trials, research, and cognitive screening.
There is growing interest in research to test the feasibility and reliability of administration, in MS, where SDMT is the most sensitive measure of cognitive function, assessing the reliability of remote SDMT administration for the current delivery of MS-related services across settings such as clinical care.
, clinical trials, research data collection) is critical8
.

To investigate the reliability of remote SDMT oral administration compared with traditional face-to-face administration in MS patients, an ACTRIMS study investigated test performance in 212 MS patients
.

These patients completed SDMT at two time points, with cohort 1 consisting of 75 patients who completed in-person testing at both time points (average test interval of 527 days); cohort 2 consisting of 137 patients who initially The SDMT was completed by face-to-face, followed by a second SDMT by video remote (average test interval of 520 days)
.

Pearson correlation analysis showed that there was a strong correlation between the two groups of SDMT scores at different time points: (1) face-to-face SDMT only: r=0.
86, p<0.
001; (2) face-to-face and remote SDMT: r=0.
89, p<0.
001
.

The study shows that remote SDMT is an effective and feasible form of management, and the scores for face-to-face and remote management are interchangeable8
.

Figure 3.
Pearson correlation analysis showed that there was a strong correlation between the SDMT scores of the two groups at different time points ) receptor modulators, approved in many countries for the treatment of adults with relapsing forms of MS (RMS), and their efficacy and safety have been reliably demonstrated in previous studies
.

The DAYBREAK study further explored the long-term efficacy and safety of Ozamod, and the results of the interim analysis were presented at this conference
.

It is an ongoing open-label extension study of 2494 patients with RMS who completed a phase I to III ozamod-related study who were treated with ozamod 0.
92 mg once daily (divided into There are 3 groups: converted from interferon beta-1a 30µg/week, from Ozamod 0.
46mg/day, and continued to receive Ozamod 0.
92mg/day), the average treatment time was 46.
8 months, Relapse, disability progression, number of new/expanded T2 lesions, number of gadolinium-enhanced lesions, safety and other indicators were observed and evaluated
.

RESULTS: The intention-to-treat population-adjusted annual relapse rate (ARR) was as low as 0.
103, with 75% of patients relapse-free at 3 years, and 88.
6% of patients without confirmed disability progression at 6 months
.

At month 48 of the DAYBREAK study, the adjusted mean number of new/expanded T2 lesions per scan and the number of gadolinium-enhancing lesions were lower and similar across groups
.

In terms of safety, the study showed that the safety and tolerability of Ozamod were consistent with the core phase
.

These results suggest that the efficacy of Ozamod can be maintained in the long-term with good long-term safety 9
.

Figure 4.
Intention-to-treat population-adjusted ARRs were lower in all groups.
The results of the post-hoc analysis of the SUNBEAM study were also published at this conference
.

The phase III SUNBEAM study found that Ozamod reduced plasma neurofilament light chain (pNfL) concentrations and improved cognitive processing speed (as measured by SDMT scores) compared to interferon beta-1a
.

This post hoc analysis was designed to assess the relationship between baseline and 12-month treatment with ozamod or interferon beta-1a pNfL concentrations and SDMT scores in the SUNBEAM study, showing that ozamod compared to interferon beta-1a Greater reduction in pNfL concentration (nominalP < 0.
0001) and improved SDMT score (nominalP = 0.
0019)
.

These results suggest that Ozamod is more beneficial than interferon beta-1a in improving cognitive impairment in patients 10
.

Figure 5.
Compared with interferon beta-1a, Ozamod significantly reduced pNfL concentration and improved SDMT score.
Director, head of the Neurological and Internal Imaging Multidisciplinary Consultation Center
.

He is engaged in clinical and basic research on autoimmune diseases of the nervous system, rare diseases and difficult and critical diseases, and has extensive experience in clinical, neuroimaging, and multidisciplinary diagnosis and treatment
.

Member of the Neuroimmunology Group of the Neurology Branch of the Chinese Medical Association; Standing Committee Member of the Neuroimmunology Branch of the Chinese Society of Immunology; Deputy Head of the Neuroimmunology Group of the Neurology Branch of the Chinese Medical Doctor Association; Youth Deputy Director of the Neurology Professional Committee of the Army, Neuroimmunology Group Deputy Head
.

Participated in the research of key topics such as the Army Key, Wu Jieping Fund, National High-tech Research and Development Program (863), National Science and Technology Support Program (973); published more than 70 papers; 20 SCI papers
.

Author of "Chinese Expert Consensus on Multiple Sclerosis Diagnosis and Treatment" and "Chinese Guidelines for Diagnosis and Treatment of Neuromyelitis Optica Spectrum Diseases"
.

He has won 2 second prizes for military scientific and technological achievements and the second prize for Beijing Medical Science and Technology
.

MS is a chronic and disabling disease.
Various symptoms including physical function decline and cognitive dysfunction seriously affect the daily life and work of patients.
The latest research shows that as the level of disability increases, Chinese MS patients The economic burden of the disease has increased significantly, suggesting that effective intervention measures should be taken as soon as possible in clinical practice to control the symptoms of the disease and delay the progression of disability
.

Cognitive dysfunction is one of the core clinical symptoms of MS patients, and the latest research on its mechanism has shown that chronic demyelination may lead to cognitive dysfunction in MS patients
.

Early identification of cognitive changes and the adoption of targeted treatment strategies to protect cognitive function are one of the key goals of clinical management of MS.
The assessment of cognitive function in MS patients should be a part of daily clinical practice.
SDMT is a highly sensitive A tool that can be used for early cognitive screening, remote SDMT is also an effective and feasible form of management
.

At present, there are more than 20 kinds of DMT drugs in the world, but domestic choices are still relatively limited.
There is an urgent need for new DMTs that can effectively reduce the number of recurrences, improve the progression of patients' disability, delay brain atrophy, and improve cognitive dysfunction.
The long-term research data of Moder shows that it has good efficacy and safety, and the ARR is as low as 0.
103, which means that it is possible to achieve a low recurrence rate for many years.
Compared with interferon beta-1a, it is more helpful to improve the cognitive dysfunction of patients.
, comprehensively control the condition of RMS patients, expect it to be launched in China as soon as possible, become another powerful weapon for the treatment of MS, and benefit the majority of Chinese MS patients! Reference: 1.
P333.
Economic burden associated with advancing expanded disability statusscale score (EDSS) in Chinese Multiple Sclerosis patients: Results from areal-world cross-sectional Survey.
ACRTIMS 2022.
2.
Gross HJ, Watson C.
Characteristics, burden of illness, and physical functioning of patients with relapsing-remitting and secondary progressivemultiple sclerosis: a cross-sectional US survey.
Neuropsychiatr Dis Treat.
2017;13:1349-1357.
3.
Kalb R, Beier M, Benedict RH, et al.
Recommendations for cognitive screening and management in multiple sclerosis care.
Mult Scler.
2018;24(13):1665-1680.
4.
Manca R, Sharrack B, Paling D, Wilkinson ID, Venneri A.