Table 2.

Summary of clinical and MRI efficacy in phase II clinical trials.

	Rituximab	Ocrelizumab	Ofatumumab		Ublituximab
Trial Reference	HERMES Hauser et al., 2008	Kappos et al., 2011	Sorensen et al., 2014	MIRROR (Phase IIb) Bar-Or et al., 2018	Fox et al., 2021
MS form	RRMS	RRMS	RRMS	RRMS	RMS
Trial design	Randomized, double blind, placebo-controlled, multicenter	Randomized, parallel, double blind, dose finding study, multicenter	Randomized, double blind, placebo-controlled	Randomized, double blind, placebo-controlled, multicenter	Randomized, placebo-controlled, multicenter
Treatment groups	1000 mg IV infusions of rituximab or placebo on days 1 and 15	Ocrelizumab 600 mg 2 cycles (300 mg + 300 mg and 600 mg + 0 mg) Ocrelizumab 1000 mg (1000 mg + 1000 mg and 1000 mg + 0 mg) Placebo (only 1 cycle then ocrelizumab 600mg) Interferon beta-1a (only 1 cycle 30μg per week then ocrelizumab 600 mg)	2 IV infusions of either ofatumumab (100, 300, or 700 mg) or placebo 2 weeks apart	Placebo or subcutaneous ofatumumab 3 mg, 30 mg, or 60 mg every 12 weeks or 60 mg every 4 weeks	Ublituximab 150 mg on day 1 (1-4 hours) and then 450 or 600 mg on day 15 and week 24 (1-3 hours)
Patients (ratio)	n=104 (2:1)	n=220 (1:1:1:1)	n=38 (2:1)	n=232 (2:1:1:1:2)	n=48 (3:1)
Follow-up	48 weeks	96 weeks	Two 24-week treatment periods	24 weeks	48 weeks
Primary objective	Number of gadolinium-enhancing lesions T1-weighted MRI brain scans at weeks 12, 16, 20, and 24	Total number of gadolinium-enhancing T1 lesions observed on brain MRI scans at weeks 12, 16, 20, and 24	Cumulative number of new gadolinium-enhancing lesions, T2 lesions, and T1 hypointense lesions measured on monthly MRI.	Cumulative number of new gadolinium-enhancing lesions at week 12 (based on T1-weighted MRI scans at weeks 4, 8, and 12)	Responder rate, defined as the proportion of ublituximab-treated patients with ≧̸95% peripheral CD19+ B-cell depletion from baseline within 2 weeks after the second ublituximab infusion
ARR (mean, 90% or 95% CI)	Between week 0 and 24 weeks rituximab vs placebo: 0.3 vs. 0.8, p=0.04 Between 0 and 48 weeks rituximab vs placebo: 0.4 vs. 0.7, p=0.08	Annualized relapse rate by week 24: Ocrelizumab 600 mg: 0.13 (0.53-0.29); p=0.0005 versus placebo; p=0.03 versus interferon beta-1a Ocrelizumab 2000 mg: 0.17 (0.05-0.3); p=0.0014 versus placebo; p=0.09 versus interferon beta-1a Placebo: 0.64 (0.43-0.94) Interferon beta-1a: 0.36 (0.22-0.60)	n/a	n/a	ARR at baseline: 1.45 ARR at week 48: 0.07
Gadolinium-enhancing T1 lesions (mean;SD or 95% CI)	Mean number of lesions at weeks 12, 16, 20, and 24: Rituximab: 0.5 ± 2.0 as Placebo: 5.5 ± 15.0 (p<0.001) Mean number of new lesions Rituximab: 0.2 ± 0.4 Placebo: 4.5 ± 12.6 (p<0.001)	Total number of galodinium-enhancing T1 lesions over weeks 12, 16, 20, and 24: Ocrelizumab 600 mg: 0.6; p<0.0001 versus placebo or interferon beta-1a Ocrelizumab 2000 mg: 0.2; p<0.0001 versus placebo or interferon beta-1a Placebo: 5.5 (12.5) Interferon beta-1a: 6.9 (16.0)	For weeks 0 –24 New T1 GdE lesions (p< 0.001) ofatumumab (-4.0) versus Placebo (-1.0), Total number of T1 GdE lesions (p< 0.001), ofatumumab (= -6.0) versus Placebo (= 0.0)	65% reduction of cumulative Gd-enhancing lesions for all ofatumumab groups between weeks 0 and 12 (rate ratio 0.35, 95% CI 0.221–0.548, p < 0.001)	Mean number at baseline: 3.63 ( ± 7.80). At weeks 24 and 48, no new or persisting lesion (100% reduction from baseline; p=0.003).
MRI T2 lesions (mean; SD or 95% CI)	Changes in lesions volume At week 24: rituximab: −163.1 ± 1187.6 placebo: 436.3 ± 1358.4 (p=0.008) At week 36: rituximab: −175.4 ± 1188.1 placebo: 417.8 ± 1305.1 (p=0.004)	Change in volume of T2 lesions: Ocrelizumab 600 mg: -841.4 (2702.2); p=0.2 versus placebo Ocrelizumab 2000 mg: -578.1 (2109.2); p=0.2 versus placebo Placebo: -114.0 (1400.8) Interferon beta-1a: 996.7 (4418.1) Total number of new or enlarging T2 lesions at week 24: Ocrelizumab 600 mg: 0.0 (0.1); p<0.0001 versus placebo Ocrelizumab 2000 mg: 0.0 (0.1); p<0.0001 vs placebo Placebo: 1.4 (3.3) Interferon beta-1a: 1.8 (5.2)	New and/or enlarging T2 lesions (p< 0.001) ofatumumab (-4.0) versus placebo (0.00).	n/a	Mean T2 lesion volume at baseline: 15,410 mm3 7.3% decrease by week 24 from baseline (p=0.006) 3.6% decrease between week 24 and week 48 (p=0.019) Total decrease from baseline of 10.6% (p=0.002) New or enlarging T2 lesions from baseline to week 24: 0.20 ( ± 0.43) New or enlarging T2 lesions from week 24 to week 48: 0.04 ( ± 0.29)

n/a, not applicable.