STUDY: Higher-intensity DMTs may slow brain atrophy in MS

[ActiveMSers]

Effect of disease-modifying therapies on subcortical gray matter atrophy in multiple sclerosis

Elias S Sotirchos, Natalia Gonzalez-Caldito, Blake E Dewey, ...

https://doi.org/10.1177/1352458519826364

Abstract

Background:
The effects of disease-modifying therapies (DMTs) on region-specific brain atrophy in multiple sclerosis (MS) are unclear.

Objective:
To determine the effects of higher versus lower efficacy DMTs on rates of brain substructure atrophy in MS.

Methods:
A non-randomized, observational cohort of people with MS followed with annual brain magnetic resonance imaging (MRI) was evaluated retrospectively. Whole brain, subcortical gray matter (GM), cortical GM, and cerebral white matter (WM) volume fractions were obtained. DMTs were categorized as higher (DMT-H: natalizumab and rituximab) or lower (DMT-L: interferon-beta and glatiramer acetate) efficacy. Follow-up epochs were analyzed if participants had been on a DMT for ⩾6 months prior to baseline and had at least one follow-up MRI while on DMTs in the same category.

Results:
A total of 86 DMT epochs (DMT-H: n = 32; DMT-L: n = 54) from 78 participants fulfilled the study inclusion criteria. Mean follow-up was 2.4 years. Annualized rates of thalamic (−0.15% vs −0.81%; p = 0.001) and putaminal (−0.27% vs −0.73%; p = 0.001) atrophy were slower during DMT-H compared to DMT-L epochs. These results remained significant in multivariate analyses including demographics, clinical characteristics, and T2 lesion volume.

Conclusion:
DMT-H treatment may be associated with slower rates of subcortical GM atrophy, especially of the thalamus and putamen. Thalamic and putaminal volumes are promising imaging biomarkers in MS

[ActiveMSers]

This study dovetails on the one above. While stronger therapies work better, they are not being prescribed as often... -D

Trends in the use of Highly Effective Disease Modifying Treatments in Multiple Sclerosis
over 12 years across 10 Sites

Marisa McGinley, et al

Objective: To determine changes in prescribing practices of highly effective treatments (HET) in multiple sclerosis (MS) over time across multiple sites.

Background: The treatment landscape for MS has dramatically changed. There is currently no universally accepted treatment paradigm. There are two ongoing PCORI funded trials (DELIVER-MS and TREAT-MS) that aim to directly compare initial use of low/moderate efficacy treatments (LMT) vs. HET approaches in early relapsing remitting MS (RRMS). The optimal treatment strategy is not known, which may result in significant practice variability.

Design/Methods: : Demographics, MS disease history, and iPad® based neuroperformance tests were collected from 10 academic MS centers in the US and Europe utilizing the MSPATHS database. The proportion of HET and LMT was assessed yearly since 1993 through 2018 in the entire RRMS population and treatment naïve population. HET was classified as use of natalizumab, alemtuzumab, ocrelizumab, or rituximab. LMT was classified as use of any other FDA approved therapy for RRMS. Results: 5520 RRMS patients on treatment were identified in MS PATHS (age 46± 11.5 years, female 75%, white 63.5%, education >12 years 72.7%, disease duration 11±8 years, PDDS 0, full time employment 54%, private insurance 58.3%, treatment naïve 37.6%). In the entire RRMS population the first utilization of HET was in 2006 at 27.3% and this has increased to 43.8% in 2018. In a treatment naïve population (n=2060) the first utilization of HET was in 2009 at 9.5% and has increased to 32.3% in 2018. Significant variability was also observed in the proportion of patients treated with HET across different sites.

Conclusions: Although the utilization of HET has increased in MS it remains the minority of DMTs used and currently only accounts for about a third of first line treatments used. Treatments strategies continue to significantly vary and more evidence is needed to inform treatment approaches.

[ActiveMSers]

And another study. Younger the better... -D

Higher Efficacy Therapies Appear to have a Disproportionately Larger Effect in Younger
Patients with Multiple Sclerosis

Brandi Vollmer, et al
University of Colorado

Objective: Identify baseline characteristics associated with future disease activity in multiple sclerosis(MS) patients comparing oral and infusible disease modifying therapies(DMTs).

Background:
Our previous studies demonstrated higher effectiveness with infusible DMTs (rituximab, natalizumab) over oral DMTs (fingolimod, dimethyl fumarate), however, many patients do well on oral DMTs. Identifying patients likely to experience disease activity in clinical practice is still a challenge.

Design/Methods: Relapsing-remitting MS Patients prescribed fingolimod, dimethyl fumarate, natalizumab or rituximab at the Rocky Mountain MS Center at the University of Colorado were followed for 24 months or until drug discontinuation. Patients receiving oral (fingolimod, dimethyl fumarate) versus infusible (natalizumab, rituximab) were evaluated for disease activity, defined as experiencing a clinical relapse, new T2 lesion and/or gadolinium enhancing lesion(GdE).

Results:
Of the 1004 patients analyzed, 509 received oral DMTs and 495 received infusible DMTs. In the oral DMT group, 36.4% experienced disease activity versus 21.2% in the infusible DMT group. Oral patients experiencing disease activity were younger(p<0.001), had lower disease duration(p=0.010) and were more likely to have GdE on baseline MRI(p=0.015) than those who did not experience disease activity. Those <45 years had greater odds of experiencing disease activity overall(OR=2.06,p<0.001), clinical relapse(OR=2.20,p=0.008), new T2
lesion(OR=2.95,p<0.001), or
dE(OR=3.35,p<0.001) compared to those ≥45 years. Infusible patients experiencing disease activity were younger(p=0.021) and were more likely to have GdE on baseline MRI(p=0.036). Those <45 years had similar odds of experiencing disease activity overall(OR=1.35,p=0.232), clinical relapse(OR=1.16,p=0.726), new T2 lesion(OR=1.02,p=0.952), or GdE(OR=2.662,p=0.2013) compared to
those ≥45 years. The odds of experiencing disease activity with oral versus infusible DMTs is greater in younger patients (<45 years:OR=2.67,p<0.001) than older patients (≥45 years:OR=1.75,p=0.033).

Conclusions: Future disease activity is independently associated with younger patients and GdE lesions at baseline. There is a benefit to treating patients ≥45 years of age. Higher efficacy therapies appear to have a disproportionately larger effect on younger patients.