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CHIMES

Two Years of Ocrelizumab Treatment in Black and Hispanic People with Multiple Sclerosis in CHIMES: A Single-Arm Clinical Trial

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Year of Publication: 2026

Authors: Amezcua L, Reder AT, Bernitsas E, ..., Williams MJ; for the CHIMES Study Group

Journal: Annals of Neurology

Citation: Ann Neurol. 2026 Jul 30;100(4):793-807

Link: https://doi.org/10.1002/ana.78290

Clinical Question

Are ocrelizumab effectiveness and safety outcomes in Black and Hispanic people with relapsing MS consistent with those observed in predominantly white pivotal trial cohorts?

Study Overview

Objective

To evaluate the effectiveness and safety of ocrelizumab in self-identified Black and Hispanic people with relapsing multiple sclerosis, populations historically underrepresented in pivotal MS trials.

Study Summary

50.5% of CHIMES participants achieved NEDA-3 at week 48 and 46.7% at week 96 (vs 55.5% and 48.5% in OPERA I/II)
94.5% free from 24-week confirmed disability progression, 95.1% free from relapse, 95.6% free from T1 Gd+ lesions at week 48
Adjusted annualized relapse rate 0.04 (BpwRMS) and 0.02 (HpwRMS) at week 96 — substantially lower than OPERA I/II (0.16)
Serious AEs in 8.2%; 2.2% discontinued for AEs; infusion reactions more common in Hispanic (42.0%) vs Black (29.2%) participants
Propensity-matched sensitivity analysis showed no significant difference in NEDA-3 vs matched white OPERA participants

Intervention

Ocrelizumab 2 x 300 mg IV infusions 14 days apart, then 600 mg every 24 weeks for 96 weeks.

Patients per Arm

Black 113, Hispanic 69, total 182

Bottom Line

In this single-arm phase 4 trial, ocrelizumab effectively controlled disease activity in Black and Hispanic people with relapsing MS, with NEDA-3, disability progression, relapse rates, and safety outcomes consistent with the pivotal OPERA I/II trials. CHIMES was not designed to establish equivalence or noninferiority; a post hoc propensity-matched analysis at week 96 (not for the week-48 primary endpoint) found no significant NEDA-3 difference vs white OPERA participants, and infusion-related reactions in Hispanic participants (42.0%) and low gastrointestinal-event rates in Hispanic participants (1.4%) fell outside the OPERA I/II ranges.

        Major Points
        50.5% of CHIMES participants achieved the primary endpoint (NEDA-3) at week 48, comparable to 55.5% in OPERA I/II historical controls
94.5% were free from 24-week confirmed disability progression and 95.1% free from relapse at week 48
Adjusted annualized relapse rate at 96 weeks was ~0.02-0.04 across CHIMES cohorts vs 0.16 in OPERA I/II
Propensity-score matched sensitivity analysis showed no significant NEDA-3 difference between CHIMES and white OPERA participants
Infusion-related reactions were more frequent in Hispanic (42.0%) vs Black (29.2%) participants; gastrointestinal AEs more frequent in Black (23.0%) vs Hispanic (1.4%) participants
Serum NfL levels decreased by ~47-49% over 96 weeks, with greater reductions than seen in OPERA I/II
Genetic ancestry aligned with self-identified race/ethnicity; HLA-DRB1*15:03 allele more frequent in Black (29.7%) and HLA-DRB1*15:01 more frequent in Hispanic (19.1%) participants
Novel trial design elements (childcare, transportation, linguistic support; sites in US, Puerto Rico, and Kenya) successfully recruited 182 participants from underrepresented populations

      

Design

Study Type: Prospective, open-label, single-arm, phase 4 trial

Randomization:

Blinding: Open-label

Allocation: Single-arm (no randomization)

Enrollment Period: First patient enrolled July 30, 2020; 48-week primary completion December 15, 2022

Follow-up Duration: 96 weeks (2 years); data cut December 15, 2023; optional 3-year extension available

Centers: 0

Countries: United States, Puerto Rico, Kenya

Sample Size: 182

Analyzed: 182

Analysis: Intention-to-treat; modified intent-to-treat for NEDA-3 (excluding participants who discontinued and withdrew due to lack of effectiveness or death); post hoc 1:1 propensity score matching with white OPERA participants

Power Calculation: Targeted enrollment of 150 participants to achieve 95% CI of 30.2%-46.3% around estimated 38% NEDA-3 (based on CHORDS study), using exact Clopper-Pearson method

Registration: NCT04377555

Inclusion Criteria

Self-identified Black/African American or Hispanic/Latino
Age 18-65 years
Relapsing multiple sclerosis meeting US prescribing criteria
EDSS score 0-5.5
Up to 2 prior disease-modifying therapies allowed with minimal washout
Prior anti-CD20 therapy allowed if >5 years before enrollment and peripheral CD19+ B cells returned to normal range
Independent medical assessment and treating neurologist decision that ocrelizumab was the most appropriate treatment

Exclusion Criteria

Exclusion criteria regarding comorbidity described in eMethods (not detailed in main text)

Arms

Field	Ocrelizumab (all CHIMES)	BpwRMS subgroup	HpwRMS subgroup
N	182	113	69
Intervention	Ocrelizumab: 2 x 300 mg IV infusions 14 days apart, then 600 mg IV every 24 weeks	Ocrelizumab (same regimen)	Ocrelizumab (same regimen)
Duration	96 weeks (with optional 3-year extension)	96 weeks	96 weeks

Outcomes

Outcome	Type	Control	Intervention	HR / OR / RR	P-value
Proportion of participants with no evidence of disease activity in 3 components (NEDA-3): free from protocol-defined relapse, 24-week confirmed disability progression, and disease activity on MRI (T1 Gd+ lesions and new/enlarging T2 lesions)	Primary	OPERA I/II reference: 55.5% (n=431/777) — unmatched historical benchmark	CHIMES: 50.5% (n=92/182); 95% CI 43.1-58.0; BpwRMS 46.0% (52/113), HpwRMS 58.0% (40/69)	Comparable to unmatched OPERA I/II historical benchmark at week 48; the post hoc propensity-matched sensitivity analysis vs white OPERA participants was conducted at week 96 (not for the week-48 primary endpoint) and showed no significant NEDA-3 difference	not reported
NEDA-3 at week 96 (all CHIMES)	Secondary	46.7% (95% CI 39.3-54.2); BpwRMS 40.7%, HpwRMS 56.5%; OPERA I/II 48.5%
NEDA-3 re-baselined to week 24, weeks 24-96 (all CHIMES)	Secondary	76.9%; BpwRMS 73.5%, HpwRMS 82.6%; OPERA I/II 73.8%
Free from 24-week confirmed disability progression (0-48 weeks)	Secondary	CHIMES 94.5% (95% CI 90.1-97.3); BpwRMS 94.7%, HpwRMS 94.2%; OPERA 98.5%
Free from 24-week confirmed disability progression (0-96 weeks)	Secondary	CHIMES 90.7% (95% CI 85.5-94.5); BpwRMS 88.5%, HpwRMS 94.2%; OPERA 91.1%
Free from relapse (0-48 weeks)	Secondary	CHIMES 95.1% (95% CI 90.8-97.7); BpwRMS 94.7%, HpwRMS 95.7%; OPERA 87.6%
Free from relapse (0-96 weeks)	Secondary	CHIMES 92.3% (95% CI 87.4-95.7); BpwRMS 90.3%, HpwRMS 95.7%; OPERA 80.0%
Free from T1 Gd+ lesions (0-48 weeks)	Secondary	CHIMES 95.6% (95% CI 91.5-98.1); BpwRMS 94.7%, HpwRMS 97.1%; OPERA 96.9%
Free from T1 Gd+ lesions (0-96 weeks)	Secondary	CHIMES 96.2% (95% CI 92.2-98.4); BpwRMS 94.7%, HpwRMS 98.6%; OPERA 95.0%
Free from new/enlarging T2 lesions (0-48 weeks)	Secondary	CHIMES 52.7% (95% CI 45.2-60.2); BpwRMS 46.0%, HpwRMS 63.8%; OPERA 64.9%
Free from new/enlarging T2 lesions (0-96 weeks)	Secondary	CHIMES 52.2% (95% CI 44.7-59.6); BpwRMS 46.0%, HpwRMS 62.3%; OPERA 62.8%
96-week adjusted annualized relapse rate	Secondary	BpwRMS 0.04 (95% CI 0.02-0.09); HpwRMS 0.02 (95% CI 0.01-0.08); OPERA I/II 0.16 (95% CI 0.12-0.20)
EDSS score over 96 weeks	Secondary	Remained stable; trends similar to OPERA I/II
Timed 25-foot walk over 96 weeks	Secondary	Stable in both CHIMES and OPERA I/II
9-hole peg test over 96 weeks	Secondary	Highly variable; different trajectories in CHIMES vs OPERA I/II
T2 lesion volume change at week 96	Secondary	Significant decrease from baseline (p < 0.001)
Total brain atrophy rate at week 48	Secondary	Within reported annualized percent change of healthy controls (-0.24% [-0.50 to 0.01])
Thalamic volume change over 2 years	Secondary	Reduced by <2%, similar to OPERA I/II
Serum NfL change over 96 weeks	Secondary	BpwRMS -47.3% (SD 32.6%); HpwRMS -49.2% (SD 33.0%); greater reductions than OPERA I/II
CD19+ B cell depletion	Secondary	Rapid, sustained depletion to <5 cells/uL
CD3+ T cell levels	Secondary	Overall unchanged
Serum CXCL13 and GFAP	Secondary	Remained stable during ocrelizumab treatment
Any adverse event	Safety	CHIMES 87.9% (BpwRMS 90.3%, HpwRMS 84.1%); OPERA I 80.1%, OPERA II 86.3%
Serious adverse events	Safety	CHIMES 8.2% (n=15); OPERA I 6.9%, OPERA II 7.0%
AE leading to dose modification or interruption	Safety	CHIMES 17.6% (n=32); OPERA I 3.2%, OPERA II 3.8%
Discontinuation due to AEs	Safety	CHIMES 2.2% (n=4)
Death	Safety	1 Black participant died day 556 due to small bowel obstruction and bowel necrosis (OPERA II: 1 fatality due to suicide)
Infections	Safety	CHIMES 53.3% overall (BpwRMS 57.5%, HpwRMS 46.4%); OPERA I 59.6%, OPERA II 60.2%
Infusion-related reactions vs OPERA	Safety	HpwRMS 42.0% exceeded both OPERA I (30.9%) and OPERA II (37.6%); BpwRMS 29.2% within OPERA range
Gastrointestinal disorders vs OPERA	Safety	BpwRMS 23.0% similar to OPERA I 19.1% / OPERA II 22.3%; HpwRMS 1.4% substantially below OPERA range

Criticisms

Single-arm, open-label design with no internal control; comparisons rely on historical OPERA I/II data with differing baseline characteristics
Study was not designed to support direct comparisons between racial or ethnic cohorts
Sample size (N=182) exceeded 150-participant target but remains modest for characterizing rare outcomes
Post hoc analyses (NEDA-3 re-baselined to week 24; propensity matching to OPERA) were not prespecified
Higher AE-related dose modification/interruption rate (17.6%) vs OPERA (3.2-3.8%) suggests possible differences in AE management or reporting between studies
Ancestry inference using ADMIXTURE with 1000 Genomes reference may not fully capture population-specific genetic diversity
Race and ethnicity are observable but confounded with unmeasured factors (epigenetics, socioeconomic status)

Funding

not reported

Based on: CHIMES (Annals of Neurology, 2026)