Background

Prior studies suggested comparable effectiveness of dimethyl fumarate (DMF) and fingolimod (FTY) in multiple sclerosis (MS) using relapses and traditional MRI metrics. We expanded on these assessments with new outcomes, while also accounting for comorbidities.

Objectives

Compare the real-world effectiveness of DMF vs. FTY with standardized neuroperformance, MRI, and biomarker (serum neurofilament light [sNfL]) measures.

Methods

Patients were eligible if on DMF or FTY at enrollment in the MS Partners Advancing Technology and Health Solutions (MS PATHS) network with ≥1 year of follow up and ≥1 MRI in the previous year. Sensitivity analysis included a sub-group of patients who initiated DMF or FTY within 2 years prior to MS PATHS. Propensity score weighting model covariates included demographics, MS disease history parameters, clinical and radiographic characteristics, cardiovascular disease, and diabetes. Generalized estimating equation (GEE) models assessed the differences in means and in 1-year change in neuroperformance and MRI outcomes. Logistic regression models compared sNfL with age-adjusted normative thresholds.

Results

644 DMF and 564 FTY patients had neuroperformance data, 194-354 DMF and 201-385 FTY patients had MRI assessments, 152 DMF and 118 FTY patients had NfL samples. The number of follow-up assessments was comparable between groups (approximately 2 clinical, 2 MRI, and 1 biomarker). Mean time (SD) since treatment initiation was 2.2 (1.5) years for DMF and 2.6 (2.1) years for FTY. No differences were observed in the means or slopes of change for any of the analyzed outcomes. Differences in slopes of change were minimal for processing speed (0.06, p=0.8), manual dexterity (-0.1, p=0.5), walking speed (-0.03, p=0.7), contrast sensitivity (-0.03, p=0.9), patient-determined disease steps (0.02, p=0.5), relapses (0.001, p=0.9), brain parenchymal fraction (0.0003, p=0.3), new T2 lesions (0.3, p=0.1), Gd+ lesions (0.1, p=0.1), and grey matter fraction (0.002, p=0.2). There was no difference in the proportion of patients with elevated sNfL (p=0.12). The sub-group consisted of 123 DMF and 130 FTY patients with mean time (SD) since treatment initiation of 10.2 (6.9) and 10.9 (7.2) months, respectively. Subgroup sensitivity analyses showed similar findings.

Conclusions

DMF and FTY demonstrated similar effectiveness on standardized quantitative neuroperformance, MRI, and biomarker outcomes in a heterogeneous, real-world cohort.

Supported by: Biogen

Background

Diroximel fumarate (DRF) is an oral fumarate recently approved in the United States for relapsing forms of multiple sclerosis (MS). DRF demonstrated favorable gastrointestinal (GI) tolerability in clinical studies of MS patients (pts). Discontinuations due to GI adverse events (AEs) were low (0.7%) in an open-label 2-year study. In a randomized study versus dimethyl fumarate (DMF), fewer pts reported GI AEs (35%, 88/253 DRF vs 49%,123/251 DMF) and GI AEs leading to discontinuation (0.8% DRF vs. 4.8% DMF); GI AEs were less frequently reported as moderate/severe for DRF (23%, 20/88) vs DMF (40%, 49/123). It is important to characterize DRF persistence in a real-world setting and effectiveness across different patient types and geographies.

Objectives

To describe the novel design of the DRF EXPERIENCE (EXPloring diroximEl fumarate Real-world experIENCE) Study Initiative.

Methods

A Phase IV DRF study should collect data on meaningful real-world outcomes, including treatment persistence, real-world tolerability, and clinical effectiveness, including cognitive changes, to align with evolving treatment goals. As DRF was designed to reduce treatment burden, impact on quality of life should also be assessed. Country-specific nuances due to unique healthcare environments, ethnicity, and cultural considerations diminish the utility of a single-study design.

Results

The DRF EXPERIENCE Study Initiative uses a novel design comprising 4 individual studies, each conducted in different regions but anchored by a core protocol to characterize the early experience in pts initiating DRF per routine care. The core protocol defines a set of required assessments for each study, but also allows flexibility to include others that address country-specific research questions. The primary objective is to characterize persistence to DRF at 1 year. Core protocol assessments include relapse, disability, cognitive changes, and pt-reported Neuro-QoL. Each study will enroll ~200 pts; the pooled total sample size of ~800 will improve ability for subgroup analyses. Pts will be followed for 2 years and include those newly initiating a disease modifying therapy (DMT) or switching from previous DMTs (including prior DMF).

Conclusions

The DRF EXPERIENCE Study Initiative uses a novel design to characterize the improved GI tolerability profile and effectiveness of DRF in MS pts in the real-world and will be informative to providers and patients when considering MS treatment goals together with the burden of therapy.

Supported by: Biogen

Background

Understanding patient-reported changes in physical, mental, and social health after starting MS therapy is important in optimizing treatment.

Objectives

Assess changes in the Quality of Life in Neurological Disorders (Neuro-QoL; NQ) questionnaire after starting natalizumab (NAT) and compare to another high efficacy therapy - ocrelizumab (OCR).

Methods

T-scores of 12 NQ domains were obtained at routine visits in the MS Partners Advancing Technology and Health Solutions (MS PATHS) network. NQ scores from visits post NAT initiation were compared to last previous NQ (baseline, BL) to calculate the annualized rate of change and the likelihood of clinically meaningful change (≥5-point) in the overall cohort and in patients with abnormal BL NQ (T-score worse than 50; 36%-76% of the population). Subgroup analyses in NAT- and OCR-treated patients were conducted with multivariate mixed-effects regression models after propensity score weighting and adjustment for antidepressants, year and drug*year interaction.

Results

164 NAT patients were analyzed; mean (SD) follow-up was 6 (6) months and number of assessments was 2.3 (1.6). Significant improvements from pre-NAT BL were seen in 8 of 12 NQ domains. Patients with BL impairment had significant improvements in 10 NQ domains and higher rates of improvement compared to the overall cohort (p<0.05). In this subgroup, the largest number of patients with ≥5-point improvement was seen for positive affect and well-being (PAF) (43%), emotional and behavioral dyscontrol (EBD) (38%) and sleep disturbances (35%). In the subgroup of NAT (n=145)- and OCR (n=520)-treated patients, the annualized improvement rates were higher with NAT than with OCR, reaching statistical significance for PAF (p=0.02), sleep disturbances (p=0.003), and satisfaction with social roles and activities (SRA) (p=0.03). In patients with impaired BL NQ, significantly higher rates of improvement were seen with NAT than with OCR for EBD (p=0.01), participation in SRA (p=0.0001) and satisfaction with SRA (p=0.02). The percentage of patients with ≥5-point improvement was numerically higher with NAT than OCR for 9 of 12 NQ domains; differences in the likelihood of ≥5-point improvement were not significant.

Conclusions

NAT can lead to clinically meaningful improvements in mental and social health. Such improvements are unlikely to be primarily driven by expectation bias as their magnitude exceeded improvements with another high-efficacy therapy (OCR).