Table 2.
Clinical trials assessing treatment with ocrelizumab in patients with MS
| References | Number of patients | Trial design | Clinical findings | MRI findings | Adverse effects |
|---|---|---|---|---|---|
| Kappos et al. [40] | 220 RRMS | Phase II, randomized, parallel, double-blind, Pbo-controlled study (48 weeks) | ↓ ARR with OCR (low dose = 0.13; high dose = 0.17) vs Pbo (0.64) and INFβ-1a (0.36) | ↓ Gd+ lesions with 600 and 2000 mg OCR (0.6 and 0.2, respectively) vs Pbo (5.5) and INFβ-1a (6.9) |
↑ IARs with OCR vs Pbo (44% vs 9%) No ↑ serious AE Similar rate of infections |
| Hauser et al. [2] |
821 RRMS (OPERA I) 835 RRMS (OPERA II) |
Phase III, randomized, double-blind, active-controlled, parallel group studies (OPERA I and OPERA II) (96 weeks) |
↓ ARR with OCR (46% and 47%, p < 0.001) vs IFN-β1a ↓ proportion of patients with 3-month CDP with OCR (43% and 37%, p < 0.05) |
↓ Gd+ lesions (94% OPERA I; 95% OPERA II, p < 0.001) ↓ new/enlarged T2 lesions (77% OPERA I; 83% OPERA II, p < 0.001) with OCR vs INFβ-1a ↓ percentage of brain volume loss from week 24 to 96 in OPERA I (− 0.57% vs − 0.74%, p = 0.004) but not in OPERA II (− 0.64% vs − 0.75%, p = 0.09) |
↑ IARs 34% OCR vs 10% INFβ-1a or Pbo ↑ infections 59.9% with OCR (vs 54.3% INFβ-1a) in OPERA I, and 60.2% (vs 52.5% with INFβ-1a) in OPERA II → ↑ upper respiratory tract infections with OCR No ↑ serious AE ↑ neoplasm OCR (0.4%) vs INF-β-1a (0.2%) |
| Montalban et al. [2] | 732 PPMS | Phase III, double-blind, randomized, Pbo-controlled, parallel group study (ORATORIO) (120 weeks) | ↓ proportion of patients with 3-month CDP (32.9% OCR vs 39.3% Pbo, p = 0.03) and 6-month CDP (29.6% vs 35.7%, p = 0.04) |
↓ 34% T2 lesions from b to week 120 (mean change, − 3.4% with OCR vs 7.4% with Pbo, p < 0.001) ↓ loss of brain volume (− 0.90 with OCR vs − 1.09 with Pbo, p = 0.02) |
↑ IARs with OCR (40%) vs Pbo (26%) ↑ infections with OCR (71.4%) vs Pbo (69.9%) → ↑ upper respiratory tract infections with OCR No ↑ SAE ↑ neoplasm with OCR (2.3%) vs Pbo (0.8%) |
| Turner et al. [46] | 1656 RRMS | Phase III, randomized, double-blind, active-controlled, parallel group studies (pooled OPERA I and OPERA II) (96 weeks) | ↓ ARR and NEDA-3 re-baselined at week 24 in patients aged < 40 years or with ≥ 1 Gd+ lesion at b with OCR | ↓ Gd+ lesions in patients aged < 40 years or with ≥ 1 Gd+ lesion at b with OCR | – |
| Ellwardt et al. [82] | 210 MS (155 RRMS/SPMS, 55 PPMS) | Retrospective, single-center (median follow-up 200 days) | 13% of patients experienced a relapse and 5% experienced a 12-week CDP | – |
22% AE, 9% IARs Minor infections (8%) and 2 cases of a prolonged herpes labialis 1 case of toxic drug-induced hepatopathy |
| Hauser et al. [3] | 702 RRMS | Open-label extension, phase-III trials (OPERA I and OPERA II) |
↓ proportion of patients with 6 months CDP (16.1% with OCR/OCR vs 21.3% with IFN-β-1a/OCR at y5, p = 0.014) NEDA-3 = 65.4% with OCR/OCR vs 55.1% with IFN-β-1a/OCR (p < 0.001) |
Sustained suppression of new brain MRI lesion activity from years 3 to 5. ↓whole brain volume loss at 5 years vs b in those starting OCR earlier (OCR/OCR = − 1.87% vs IFN-β-1a/OCR = − 2.15%; p < 0.01) | AE consistent with past reports and no new safety signals emerged with prolonged treatment |
| Hartung et al. [44] | 678 RRMS | Open-label, prospective, single-arm, phase-IIIb study (ENSEMBLE) |
92.8% of patients free from clinical disease activity NEDA-3 = 84.8% after 1 year of treatment |
91.3% of patients free from MRI disease activity | AE consistent with past reports |
| Wiendl et al. [45] | 680 RRMS | Phase-IIIb study (CASTING) |
80.4% of patients free from clinical disease activity NEDA-3 = 74.8% after 2 years of treatment |
91.5% of patients free from MRI disease activity | AE consistent with past reports |
| Wolinsky et al. [47] | 732 PPMS | Open-label extension, phase-III trial (ORATORIO) (144 weeks) | ↓ proportion of patients with 24 weeks CDP (EDSS: 51.7% vs 64.8%, p = 0.002; 9-hole peg test: 30.6% vs 43.1% p = 0.003) with OCR vs Pbo |
↓ T2 LV (0.4% vs 13.0%, p < 0.0001) ↓ T1 LV (36.7% vs 60.9%, p < 0.001) with OCR vs Pbo ↓ rates of whole brain (− 3.1% vs − 3.4%; p = 0.13) and cortical gray matter atrophy (− 2.5% vs − 2.6; p = 0.38) from b to week 144 |
AE consistent with past reports |
AE adverse events, ARR annualized relapse activity, CDP confirmed disability progression, DMTs disease-modifying therapies, EDSS expanded Disability Status Scale, Gd+ gadolinium-enhancing, IARs infusion-associated reactions, IFN-β1a interferon-β1a, LV lesion volume, NEDA-3 no evidence of disease activity 3, OCR ocrelizumab, Pbo placebo, PPMS primary progressive multiple sclerosis, RRMS relapsing–remitting multiple sclerosis, SPMS secondary progressive multiple sclerosis