Ocrelizumab Effective in Stabilizing MS Disease Progression Across Diverse Group of Patients

Amanda Frisosky Abuaf, MD

In a single-center retrospective study recently published in Multiple Sclerosis and Related Disorders, findings demonstrated that ocrelizumab (Ocrevus; Genentech) treatment was highly effective in stabilizing clinical and MRI measures of disease progression in patients who self-identified as Black, despite a higher baseline disability relative to White patients.¹ These results suggest a prominent role humoral immunity plays in reflecting more severe central nervous system (CNS) injuries in Black patients.

In the Black cohort (n = 83), there was overrepresentation of patients who were women (78% vs. 62%, P = .013), with a lower age (median, 45 [IQR 39–51] vs. 49 [IQR,38–58], P = .08), lower Vitamin D levels (33 [IQR,21–45) vs. 40 [IQR, 29–52], P = .002), and a higher expanded disability status scale (EDSS) (4 [IQR, 2–6] vs. 2.5 [IQR, 1–6], P = .019). Although there was no progression observed with EDSS scores, T2 lesion volume remained stable in patients during the 2-year observation period of the study.

Lead author Amanda Frisosky Abuaf, MD, assistant professor, University of Wisconsin School of Medicine and Public Health, and colleagues wrote, “Despite the scarcity of research on racial differences in MS disease manifestation, course, and therapeutic response, there is accumulating evidence that the incidence of MS in the Black population may be just as high as those of Whites, and this cohort may suffer from a disproportionately high burden of disease.”¹

Data were collected from the University of Chicago MS Database which extracted records of 229 patients (White, n = 146; Black, n = 83) and MRI data from 48 patients (White 31; Black 17). The only patients included in the study were those with relapsing remitting MS (RRMS) who had been treated with ocrelizumab between August 2017 and May 2021. The primary outcome measures were changes in the EDSS and the brain volume in patients over the course of 2 years. The scores for EDSS were analyzed as raw, ambulatory (EDSS less than 5.0) vs. ambulatory with assistance (5.5 less than or EDSS less than or 6.5) status, and EDSS severity (less than 3.0, 3.0–5.0, and less than or 5.5 less than or 6.5).

“Although socioeconomic factors such as accessibility of care and distrust of physicians have been proposed as potential explanations for delayed care and worse disease, the shorter disease duration and lower proportion of patients on prior treatment would argue against treatment delays or problematic access as contributing factors to a higher baseline EDSS score in [the Black] cohort,” Abuaf et al noted.¹

Some of the covariates that showed statistically significant effects included the lower cortical volume, as it was associated with older age (P = 0.002) and longer disease duration (P = 0.063); lower cortical thickness with older age (P = 0.062); lower thalamic volume with higher EDSS (P = 0.027); lower caudate volume with female sex (P = 0.041) and higher EDSS (P = 0.008); lower putamen volume with longer disease duration (P = 0.018); lower brainstem volume with higher EDSS (P = 0.013). There were no differences in the cortical, thalamic, caudate, putamen, and brainstem gray matter volumes nor in the cortical thickness or total lesion volume between racial groups over time.

Abuaf et al noted, “Black patients may have a more progressive disease course, which is less amenable to treatment. Imaging characteristics show a more pronounced brain volume loss and inflammatory disease activity in Black patients. Furthermore, immune mechanisms may be more robust in this population.”¹

Limitations of the study included the retrospective design, the cohort differences, the short 2-year follow up, and the use of EDSS as the main clinical outcome measure. In addition, the variables that were expected to have a significant effect on EDSS—age, disease duration, and prior treatment history—did influence the EDSS scores. Authors noted that prospective studies are needed to extend the findings to have a greater understanding of associations with disparities in disease manifestation and therapeutic response.

This study extends the findings from the phase 3 ocrelizumab clinical trials, OPERA I in II (NCT01247324; NCT01412333), both of which enrolled about 4.3% Black patients (n = 71).1In the original OPERA I and II trials, ocrelizumab showed lower annualized relapse rates (ARR) than interferon beta-1a in trial 1 (0.16 vs 0.29; 46% lowered rate; P <.001) and in trial 2 (0.16 vs 0.29; 47% lowered rate; P <.001).2 In prespecified pooled analyses, the percentage of patients with disability progression confirmed at 12 weeks was significantly lower with ocrelizumab than with interferon beta-1a (9.1% vs. 13.6%; HR, 0.60; 95% CI, 0.45 to 0.81; P<0.001), as was the percentage of patients with disability progression confirmed at 24 weeks (6.9% vs. 10.5%; HR, 0.60; 95% CI, 0.43 to 0.84; P = 0.003).

At the 2023 Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum, held February 23-25, in San Diego, Mitzi Joi Williams, MD, founder and chief executive officer of Joi Wellness Group Multiple Sclerosis Center, presented post-hoc findings from the phase 3 OPERA I and II studies. The research showed that despite a more severe disease course for non-Hispanic Black (NHB) and Hispanic or Latino (HL) patients with relapsing MS, the risk for disability progression was reduced in these populations while on ocrelizumab.³

Compared with NHW, HL patients with relapsing MS had higher 9HPT (HL, 23.8; NHW, 22.0 sec), higher 25FW (HL, 6.8; NHW, 5.4 sec) and greater BMI (HL, 25.9, NHW, 24.8 kg/m2); all P<0.05. NHB and HL groups had greater baseline CD19+ B cell counts (NHB, 273; HL, 272; NHW, 222 cells/µL), including mature naive (NHB, 177; HL, 170; NHW, 140 cells/µL), plasmablast-plasma (NHB, 5; HL, 5; NHW, 3 cells/µL) and double-negative memory B cells (NHB, 12; HL, 10; NHW, 7 cells/µL); all P<0.005. Risk of 24-week confirmed disability progression, a composite of EDSS, 9HPT, and 25FW, was significantly higher in the NHB (HR, 3.0; 95% CI, 1.4-6.5) and HL (HR, 2.3; 95% CI, 1.6-3.4; P <.0001) groups relative to NHW in the interferon beta-1a arm, but not the ocrelizumab arm.

REFERENCES
1. Abuaf AF, Javed A, Bunting SR, Carroll TJ, Reder AT, Cipriani VP. Effectiveness of ocrelizumab on clinical and MRI outcome measures in multiple sclerosis across black and white cohorts: A single-center retrospective study. Mult Scler Relat Disord. 2023;71:104523. doi:10.1016/j.msard.2023.104523
2. Hauser SL, Bar-Or A, Comi G, et al. Ocrelizumab versus interferon beta-1a in relapsing multiple sclerosis. N Engl J Med. 2017;376:221-234. doi:10.1056/NEJMoa1601277
3. Williams MJ, Boorgu DSSK, Cree BA, et al. Greater baseline disease burden and risk for disability progression in self-reported non-Hispanic Black and Hispanic or Latino individuals with relapsing multiple sclerosis: findings from OPERA I and II trials of ocrelizumab. Presented at: 2023 ACTRIMS Forum; February 23-25; San Diego, CA. Abstract P078.