CMSC 2023 Focus on RRMS: The Efficacy and Safety of Long-Term Treatments, Diet

At the 2023 Consortium of Multiple Sclerosis Centers (CMSC) Annual Meeting, several research studies on relapsing-remitting multiple sclerosis (RRMS) were presented, highlighting the efficacy and safety of long-term treatments in diverse populations to the effect of diet on mental health disorders in this patient population.

Long-Term Ocrelizumab Treatment Highlights Specific At-Risk Population

The risk for severe infection was almost twice as high in patients with RRMS, aged 55 and older, treated with ocrelizumab with an Expanded Disability Status Scale (EDSS) score of 6 or more, compared with the general population, according to real-world data from the ACAPELLA study.¹

ACAPELLA is a 6-year prospective study that compares the frequency of adverse events (AEs) in patients treated with ocrelizumab vs historic 5-year clinical trial data. The study includes patients who were exempted from phase 2 and 3 trials due to preexisting conditions, such as malignancy, hypogammaglobulinemia, advanced age and/or disability.

A total of 419 patients were enrolled and treated with the targeted monoclonal antibody for up to 11 cycles. Patients were between ages 18 to 75; 26% men, 74% women; and 21% had a baseline EDSS range of 0 to 7.5 points (median, 2.5 points).

Researchers found overall infection rate in the treated group was lower, with 49.8 cases per 100 person-years (PY), compared with 76.2 cases per 100 PY observed in the 5-year clinical trial data.

Compared with the overall population (2.1 cases per 100 PY), patients aged 55 and older with an EDSS score of 6 points or more had almost double the rate of severe infection (4.1 cases per 100 PY). When the researchers independently factored age and EDSS score, however, the risk for severe infection was not notably higher than in the comparison group.

Additionally, individuals with an EDSS of at least 6 points had a higher rate of urinary tract infections, with 29.2 cases per 100 PY vs 14.8 cases per 100 PY in the total population. Similar to the general MS population, malignancies occurred at a rate of 0.5 cases per 100 PY. In the total population, 15 individuals (3.5%) had low baseline immunoglobulin G (IgG) levels, and 12 patients (3%) with normal baseline IgG developed persistent low IgG levels.

John Corboy, MD, co-director of the Rocky Mountain Multiple Sclerosis Center at the University of Colorado Anschutz Medical Campus in Aurora, noted that the clinical implications of this research would be much more valuable if there was an age- and sex-matched comparison among patients on disease-modifying therapies (DMTs) or no DMTs.

“The fact that higher age and EDSS were not associated with a higher risk for infection suggests either infections were missed or the number of cycles received was low on average, as other similar studies have different infection outcomes,” Dr Corboy noted.

He suggests that the researchers should “Do longer-term, larger studies, and report the data in a time and dose-dependent fashion.”

Swank, Wahls Diet Helps With Anxiety, Depression in RRMS

Adopting either low saturated fat (Swank) or modified paleolithic elimination (Wahls) diet was associated with reduced anxiety and depression in patients with RRMS.²

Comorbidities such as depression and anxiety are common in patients with MS. As dietary intervention and supplementation have an established role in helping mood disorders, the researchers aimed to evaluate their utility among patients with RRMS.

Individuals with RRMS were observed for 12 weeks on their usual diet and then randomly assigned to 1 of 2 regimented diet programs (Swank diet/Wahls diet) for a duration of 24 weeks. All patients were given vitamin B9 (folate) and B12 (cobalamin) supplementation. Mood and mental health were assessed using the Hospital and Anxiety and Depression Scale (HADS) and Mental Health Inventory (MHI) across a total of 4 study visits.

The secondary objective was to identify the association and mediation effects between changes in HADS and MHI scores, along with serum levels of homocysteine, vitamin B9, and vitamin B12.

The researchers found significant improvement in HADS depression and anxiety, MHI total, and subscale scores at 12 and 24 weeks.

Notably, no association between mood scores and serum homocysteine or vitamin B12 was found (P <.05).

Changes in serum levels of homocysteine or vitamin B12 did not serve as mediators for HADS or MHU scores.

“The conclusion is that adopting the Swank or Wahls diets when combined with supplements may result in significant improvements in depression and anxiety symptoms,” said study researcher Terry Wahls, MD, a clinical professor at the University of Iowa Carver College of Medicine in Iowa City, where she conducts clinical trials, and the creator of the Wahls diet.

Dr Wahls acknowledged that “Further studies are needed to understand the links between low saturated fat and modified paleolithic elimination diet and changes in mood in the setting of MS.”

Diroximel Fumarate Has Consistent Safety Profile in Black Patients With RRMS

Diroximel fumarate demonstrated a similar reduction in relapse and safety profile in Black patients with RRMS compared with non-Black patients.

The DMT, diroximel fumarate, can be comparable to dimethyl fumarate in treating RRMS as they both share the same active metabolite. However, unlike dimethyl fumarate, diroximel fumarate is associated with fewer gastrointestinal side effects. As minority participants in clinical studies are lacking, the researchers aimed to assess the safety and efficacy of diroximel fumarate in Black patients with RRMS.

The researchers conducted an ad hoc subgroup analysis of patients who self-identified as Black in the EVOLVE-MS-1 phase 3 (ClinicalTrials.gov Identifier: NCT02634307)³, which evaluated diroximel fumarate in adults with RRMS.

Out of 1,057 patients in the study, 72 self-identified as Black. Age and sex were comparable between Black (age 42; 75% women) and non-Black patients (age 43; 72% women). The mean EDSS score was similar between both groups (2.7).

Compared with non-Black patients (n=224; 23%), Black patients (n=33; 46%) had a higher rate of treatment discontinuation; treatment discontinuation due to AEs was cited for 7 (9.7%) Black patients compared with 81 (8.2%) non-Black patients.

Similar reporting of mild or moderate AEs was observed across both groups (90% in Black patients, 89% in non-Black patients). Gastrointestinal AEs were reported by 36% of Black patients and 32% of non-Black patients. Notably, no Black patients discontinued treatment due to gastrointestinal AEs, compared with 7 (0.7%) non-Black patients.

A comparable reduction in annualized relapse rates between both groups was also found; the adjusted relapse rate was reduced by 78.2% (95% CI, 54.6%-89.5%) in Black patients from 12 months before to 96 weeks after diroximel fumarate treatment, similar to the 81.7% (95% CI, 78.5%-84.5%) reduction in non-Black patients.

By week 48, the mean number of patients free of confirmed disability progression was 93.4%, then 86.2% and 90.4% by week 96 in Black and non-Black patients, respectively.

“This is reassuring, as it suggests that Black patients with MS appear to have similar outcomes as White patients with MS when using diroximel fumarate for their MS,” said Dr Corboy. “I am reassured that diroximel fumarate is a reasonable option for Black patients with MS, but more and larger studies should be performed with all the MS DMTs.”

Ocrelizumab Leads to Favorable Outcomes in Symptoms of Treatment-Naive Patients

Patients with early-stage RRMS treated with ocrelizumab over 4 years experienced improvements in work productivity, symptom impact, and symptom limitations.

Early, effective treatment has shown long-term clinical benefits in patients with RRMS. The researchers aimed to investigate the potential impact of ocrelizumab in treatment-naive patients with RRMS.

In ENSEMBLE (ClinicalTrials.gov Identifier: NCT03085810)⁴, a multi-center, open-label, single-arm, phase 3b study, the researchers recruited patients with early-stage RRMS (aged 18-55; disease duration ≤3 years; EDSS score ≤3.5; with ≤1 clinical reported relapse[s] or ≤1 sign[s] of magnetic resonance imaging [MRI] activity in the previous 12 months). To evaluate the longitudinal effects on quality of life and daily activities, patients received ocrelizumab 600 mg weekly every 24 weeks for a total of 192 weeks.

Objective work productivity, symptom impact, and MS symptom limitations were assessed using several reporting tools, including Work Productivity and Activity Impairment (WPAI) questionnaire, 29-item Multiple Sclerosis Impact Scale (MSIS-29), and SymptoMScreen scores, respectively. These were all measured at baseline and at weeks 24, 48, 96, 144, and 192.

The ENSEMBLE population was representative of patients with early-stage RRMS (patients ≤40 years; 79.5%; 64.6% women; median age, 31.0; time since MS symptom onset, 0.78 years; time since RRMS diagnosis, 0.24 years; EDSS score, 1.50).  

A total of 81% of the enrolled patients completed the 4-year study treatment.

Work impairment reduced significantly (from 23.23% to 18.18%; P <.001), with MSIS-29 improvements in both physical (from 16.90 to 15.28; P <.05) and psychologic (from 28.81 to 21.64; P <.001) impact scale scores.

Regarding symptom limitations, SymptoMScreen total score reduced significantly (from 12.2 to 11.4; P <.05).

“Across 4 years, treatment-naive patients with RRMS treated with ocrelizumab reported improvements in work productivity, MS symptom impact, and MS symptom limitations,” the researchers concluded.

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.