Fumarates Lead to Lower Infection-Related Healthcare Resource Utilization Relative to Anti-CD20s

Kyle E. Smoot, MD

In a comparative study of nearly 2000 patients with multiple sclerosis (MS), findings showed that those on long-term fumarates (FUM) had significantly lower infection-related healthcare resource utilization (HCRU) over a 2-year follow-up than those on anti-CD20-targeting medications. Overall, these data underscored the importance of long-term risk-benefit considerations when selecting disease-modifying therapies in MS management.¹

Presented at the 2025 Consortium of Multiple Sclerosis Centers (CMSC) Annual Meeting, held May 28-31, in Phoenix, Arizona, the study was the first to compare long-term infection-related HCRU between FUM versus anti-CD20 therapies. After 1:2 propensity-scoring matching, 652 patients on FUM (dimethyl fumarate: n = 614; diroximel fumarate: n = 38) were pitted against 1304 patients on anti-CD20s such as ocrelizumab (n = 1296) and ofatumumab (n = 8). Coming into the study, the baseline demographics between the two treatment groups were balanced (standardized mean differences ≤.0.10).

Led by Kyle E. Smoot, MD, a neurologist at the Providence MS Center in Portland, Oregon, the study revealed a significantly lower number of annualized infection-related healthcare encounter rate per patient per year (PPPY) with FUM relative to anti-CD20s (1.75 vs 2.22; P <.001). In addition, the mean infection events PPPY were lower for those on FUMs compared with anti-CD20s from year 2 (2.31 vs 2.75; P = .016) to year 4+ (2.54 vs 3.64; P = .021), representing a 30% lower risk (rate ratio [RR], 0.70; 95% CI, 0.52-0.95; P = .021).

This retrospective analysis pulled from Komodo Health Claims Database from January 2016 to May 2022, using patients aged 18 to 64 with at least 1 claim for MS. Infection events were identified based on ICD-10 codes while MS relapses were identified based on a previously published algorithm. Annualized relapse rate (ARR) and HCRU were calculated as the total number of relapses or healthcare encounters observed divided by the total number of patient-years.

READ MORE: Rebound Effect Not Observed With Multiple Sclerosis Therapy Ozanimod

Additional data from the late-breaking abstract revealed that MS-related healthcare encounters were 26% lower at year 3 (P = .004) and 31% lower at year 4+ (P = .019) for those on FUMs vs anti-CD20s. Both COVID- and non-COVID-related healthcare encounter rates, assessed over the full follow-up period, were 31% and 24% lower, respectively, for FUM versus anti-CD20 therapies. Between the FUM and anti-CD20 cohorts, the RR for COVID- and non-COVID-related healthcare encounters was 0.69 (95% CI, 0.59-0.82; P <.001) and 0.86 (95% CI, 0.75-0.99; P = .038), respectively.

On relapse outcomes, the mean population-level ARR in the adjusted cohort was 0.08 (95% CI, 0.06-0.1) for FUM and 0.09 (95% CI, 0.07-0.1) for anti-CD20s, resulting in a RR of 0.93 (95% CI, 0.71-1.21; P = .575). Overall, the proportion of patients who were relapse-free at month 24 was 88.7% (95% CI, 86.3-91.1) for FUM and 87.4% (95% CI, 85.6-89.2) for anti-CD20s. At month 48, these figures dipped slightly, as 80.8% (95% CI, 76.9-85.0) reported relapse-free on FUMs and 79.8% (95% CI, 77.0-82.6) for anti-CD20s (P = .50).

In the phase 3 OPERA I and II trials, the studies that led to ocrelizumab’s approval, the most common infections were upper respiratory tract infection, nasopharyngitis, and urinary tract infection. Overall, the ocrelizumab group had higher rates of infection (56.9%-60.2%) than interferon beta-1a, the comparator drug (52.5%-54.3%). Serious infections were reported in 1.3% of ocrelizumab-treated patients vs 2.9% of interferon beta-1a-treated individuals.²

Click here for more CMSC 2025 coverage.

REFERENCES
1. Smoot K, Longbrake EE, Wesley SF, et al. Infection Rates in Patients with Multiple Sclerosis Treated Long-Term with Fumarates Versus Anti-CD20 Monoclonal Antibodies. Presented at: 2025 CMSC Annual Meeting; May 28-31. LBA09
2. Hauser SL, Bar-Or A, Comi G, et al. Ocrelizumab versus interferon beta-1a in relapsing multiple sclerosis. N Engl J Med. 2017;376(3):221–34. doi:10.1056/NEJMoa1601277