The Latest Articles on Multiple Sclerosis

Our staff editors continue to share exciting, interesting, and thought-provoking reading material in the recommended articles series.

This week, we would like to share several latest articles on Multiple Sclerosis.

Title: Impact of adherence to disease-modifying drugs in Multiple Sclerosis: A study on Italian real-world data
Authors: Laura Maria Beatrice Belotti, Mirko Di Martino, Corrado Zenesini, Luca Vignatelli, Elisa Baldin, Flavia Baccari, Ben Ridley, Francesco Nonino
Type: Research Article
Abstract:

Background
Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system requiring complex diagnostic and therapeutic management. Treatment with Disease Modifying Drugs (DMDs) is aimed at reducing relapse rate and disease disability. Few real-world, population-based data are available on the impact of adherence on relapse rate.
The objective of this study was to assess the impact of adherence to DMDs on relapses in a real-world Italian setting.

Methods
Population-based cohort study. People with MS (PwMS) older than 18 years and residing in the Emilia-Romagna region, Northern Italy, were identified through administrative databases using a validated algorithm. A Cox regression model with a time-varying exposure was performed to assess the association between level of adherence to DMDs and relapses over a 5-year period.

Results
A total of 2,528 PwMS receiving a first prescription of DMDs between 2015 and 2019 were included (average age of 42, two-thirds female). Highly adherent PwMS had a 25% lower hazard of experiencing moderate or severe relapses than non-adherent PwMS (Hazard Ratio 0.75, 95% CI 0.58 to 0.98), after adjusting for age and sex. Several sensitivity analyses supported the main result.

Conclusion
The results of our study support the hypothesis that a high level of DMD adherence in MS is associated with a lower risk of moderate or severe relapse. Therefore, choosing the DMD with which to start drug treatment and recommending adherence to treatment appear to be crucial aspects involving both physicians and patients.
Access this article: https://doi.org/10.1016/j.msard.2023.105094

Title: Aerobic Cycling Reduces Fatigue and Improves Pain in Persons with Multiple Sclerosis: A Preliminary Study
Authors: Sarah B Simmons, Donayja Harris, Alexis Skolaris, Tori Fricker, Yadi Li, Brittany Lapin, Rachel Galioto, Francois Bethoux, Susan M Linder
Type: Correspondence
Abstract:

Fatigue and pain are prevalent in persons with multiple sclerosis (PwMS), negatively impacting quality of life (QoL). Clinical management is challenging due to their multiple underlying causes. Aerobic exercise elicits central and peripheral effects, which may effectively manage MS-related symptoms. Our aim was to determine the effects of an aerobic cycling intervention on symptoms impacting QoL. Eighteen participants completed a 12-week moderate- to high-intensity aerobic cycling intervention. Participants reported significant improvements in physical fatigue, overall fatigue, pain intensity, and pain interference. Aerobic exercise should be considered as part of a multi-faceted approach to improve fatigue and pain in PwMS

Access this article: https://doi.org/10.1016/j.msard.2023.105102

Title: Implementing Shared Decision-Making for Multiple Sclerosis: The MS-SUPPORT Tool
Authors: Nananda F Col, Andrew J Solomon, Enrique Alvarez, Lori Pbert, Carolina Ionete, Idanis BerriosMorales, Jennifer Chester, Christen Kutz, Crystal Iwuchukwu, Terrie Livingston, Vicky Springmann, Hannah V. Col, Long H. Ngo
Type: Research Article
Abstract:

Background
Disease modifying therapies (DMTs) offer opportunities to improve the course of multiple sclerosis (MS), but decisions about treatment are difficult. People with multiple sclerosis (pwMS) want more involvement in decisions about DMTs, but new approaches are needed to support shared decision-making (SDM) because of the number of treatment options and the range of outcomes affected by treatment. We designed a patient-centered tool, MS-SUPPORT, to facilitate SDM for pwMS. We sought to evaluate the feasibility and impact of MS-SUPPORT on decisions about disease modifying treatments (DMTs), SDM processes, and quality-of-life.

Methods
This multisite randomized controlled trial compared the SDM intervention (MS-SUPPORT) to control (usual care) over a 12-month period. English-speaking adults with relapsing MS were eligible if they had an upcoming MS appointment and an email address. To evaluate clinician perspectives, participants’ MS clinicians were invited to participate. Patients were referred between November 11, 2019 and October 23, 2020 by their MS clinician or a patient advocacy organization (the Multiple Sclerosis Association of America). MS-SUPPORT is an online, interactive, evidence-based decision aid that was co-created with pwMS. It clarifies patient treatment goals and values and provides tailored information about MS, DMTs, and adherence. Viewed by patients before their clinic appointment, MS-SUPPORT generates a personalized summary of the patient's treatment goals and preferences, adherence, DMT use, and clinical situation to share with their MS clinician. Outcomes (DMT utilization, adherence, quality-of-life, and SDM) were assessed at enrollment, post-MS-SUPPORT, post-appointment, and quarterly for 1 year.

Results
Participants included 501 adults with MS from across the USA (84.6% female, 83% white) and 34 of their MS clinicians (47% neurologists, 41% Nurse Practitioners, 12% Physician Assistants.) Among the 203 patients who completed MS-SUPPORT, most (88.2%) reported they would recommend it to others and that it helped them talk to their doctor (85.2%), understand their options (82.3%) and the importance of taking DMTs as prescribed (82.3%). Among non-users of DMTs at baseline, the probability ratio of current DMT use consistently trended higher over one-year follow-up in the MS-SUPPORT group (1.30 [0.86-1.96]), as did the cumulative probability of starting a DMT within 6-months, with shorter time-to-start (46 vs 90 days, p=0.24). Among the 222 responses from 34 participating clinicians, more clinicians in the MS-SUPPORT group (vs control) trended towards recommending their patient start a DMT (9 of 108 (8%) vs 5 of 109 (5%), respectively, p=0.26). Adherence (no missed doses) to daily-dosed DMTs was higher in the MS-SUPPORT group (81.25% vs 56.41%, p=.026). Fewer patients forgot their doses (p=.046). The MS-SUPPORT group (vs control) reported 1.7 fewer days/month of poor mental health (p=0.02).

Conclusions
MS-SUPPORT was strongly endorsed by patients and is feasible to use in clinical settings. MS-SUPPORT increased the short-term probability of taking and adhering to a DMT, and improved long-term mental health. Study limitations include selection bias, response bias, social desirability bias, and recall bias. Exploring approaches to reinforcement and monitoring its implementation in real-world settings should provide further insights into the value and utility of this new SDM tool.
Access this article: https://doi.org/10.1016/j.msard.2023.105092

Title: Impact of automatic tools for detecting new lesions on therapeutic strategies offered to patients with MS by neurologists
Authors: Blandine Merkler, Arthur Masson, Jean Christophe Ferré, Emma Bajeux, Gilles Edan, Laure Michel, Emmanuelle Le Page, Marion Leclercq, Benoit Pegat, Simon Lamy, Goulven Le Corre, Kevin Ahrweiler, Fabien Zagnoli, Denis Maréchal, Benoît Combès, Anne Kerbrat
Type: Research Article
Abstract:

Background
Automatic tools for detecting new lesions in patients with MS between two MRI scans are now available to clinicians. They have been assessed from the radiologist's point of view, but their impact on the therapeutic strategies that neurologists offer their patients has not yet been documented.

Objectives
To compare neurologist's decisions according to whether a lesion detection support system had been used and describe variability between neurologists on decision-making for the same clinical cases.

Methods
We submitted 28 clinical cases associated with pairs of MRI images and radiological reports (produced by the same radiologist without vs. with the help of a system to detect new lesions) to 10 neurologists who regularly follow patients with MS. They examined each clinical case twice (without vs. with support system) in two sessions several weeks apart, and their patient management decisions were recorded.

Results
There was considerable variability between neurologists on decision-making (both with and without support system). When the support system had been used, neurologists more often made changes to patient management (75 % vs. 68 % of cases, p = 0.01) and spent significantly less time analyzing the clinical cases (249 s vs. 216 s, p == 3.10-4).

Conclusions
The use of a lesion detection support system has an impact not only on radiologists' reports, but also on neurologists' subsequent decision-making. This observation constitutes another strong argument for promoting the wider use of such systems in clinical routine. However, despite their use, there is still considerable variability in decision-making across neurologists, which should encourage us to refine the guidelines.
Access this article: https://doi.org/10.1016/j.msard.2023.105064

Title: Cancer Risk, Disease-Modifying Therapy, and Age in Multiple Sclerosis: A Retrospective Population-Based Cohort Study
Authors: Jamie Greenfield, Luanne M. Metz, Amir Khakban, Elisabet Rodriguez Llorian, Kristina D. Michaux, Anthony Traboulsee, Jiwon Oh, Penelope Smyth, Larry D. Lynd, Andrew G.M. Bulloch, Jeanne V.A. Williams, Scott B. Patten, CanProCo Study Group
Type: Research Article
Abstract:

Background
Long-term population-based safety studies are needed to investigate cancer outcomes in people with multiple sclerosis (MS) treated with modern disease-modifying therapy (DMT).

Objectives
To investigate if exposure to DMT increases the risk of invasive cancer in MS.

Methods
We used population-based administrative health data from Alberta, Canada between 2008-2018. DMT exposure was defined in two ways: first as exposure to any DMT, and second by DMT type (modulating, sequestering, depleting). Study outcome was time to first diagnosis of invasive cancer. Cancer risk was compared to the general population using standardized incidence ratios (SIRs) and to the unexposed MS cases using hazard ratios (HRs).

Results
The analysis included 14,313 MS cases: 5,801 (40.5%) were exposed to DMT. Median (interquartile range) follow-up was 8.4 (4.3, 10.4) years. Compared to the general population, there was no difference in cancer risk for the overall MS population (SIR: 0.94, 95% confidence interval [CI]: 0.87, 1.02) or the DMT-exposed MS cases (SIR: 0.89; 95% CI: 0.75, 1.05). Compared to unexposed MS cases, we found an interaction with age for exposure to any DMT (p=0.001) and modulating DMT (p=0.001), indicating that a difference in the risk of cancer associated with DMT depends on age. Cancer risk was not associated with exposure to sequestering DMT (HR: 1.28, 95% CI: 0.78, 2.08) or depleting DMT (HR: 2.29, 95% CI: 0.86, 6.14).

Conclusions
Cancer risk for MS patients was similar to the general population. In the MS population, the age-dependent effect of DMT for cancer risk suggests a higher risk of cancer with age 62 or older and a protective effect at younger age. Further investigation is required to clarify whether the interaction between DMT exposure and age is a causal effect.
Access this article: https://doi.org/10.1016/j.msard.2023.105091