Table 4.
Overview of the most relevant B-cell-targeting treatments currently under investigation in multiple sclerosis patients
| Target | Name and posology | References | Number of patients | Trial design | Efficacy | Safety |
|---|---|---|---|---|---|---|
| CD20 | Ublituximab (150 mg on day 1, 450 or 600 mg on day 15 and 24 weeks) | NCT02738775 [83] | 48 RRMS | Phase II (48 weeks), Pbo-controlled |
ARR 0.07 93% of the patients were relapse free at 48 weeks No patients demonstrated CDP ↓ T2 LV by 8% at 24 weeks (p = 0.004) and 10% at 48 weeks (p = 0.016) ↓ Gd+ lesions (3.8 at b vs 0 at 24 weeks, p = 0.003) |
The most common AEs were IARs that were all grade 1 or 2 No SAE No serious or opportunistic infections and no liver disease |
| CD19 | Inebilizumab (MEDI-551) (2 i.v. doses, days 1 and 15: 30, 100 or 600 mg; or single s.c. dose on day 1: 60 or 300 mg) | NCT01585766 [65] | 28 RRMS | Phase I (24 weeks) |
No relapses and no median EDSS score changes at 24 weeks ↓ new/newly enlarging T2-hyperitense (0.4 vs 2.4) ↓ Gd+ lesions (0.1 vs 1.3) ↑ proportion of patients free from new inflammatory activity (75% vs 43%) |
IARs occurring in 7 out of 21 (33.3%) RRMS patients and with upper respiratory tract and urinary tract infections, pyrexia and increased blood pressure |
| BTKi | Evobrutinib (25 mg daily, 75 mg daily or 75 mg twice daily) | NCT02975349 [69] |
228 RRMS 33 SPMS |
Phase II, double-blind, randomized, Pbo or DMF (24 weeks) |
75 mg of evobrutinib once daily: ↓ Gd+ lesions vs Pbo at 12 and 24 weeks (1.69 vs 3.85, lesion rate ratio 0.30, p = 0.005) 75 mg of evobrutinib twice daily (1.15, lesion rate ratio 0.44, p = 0.06) No difference in the ARR, relapse-free status or CDP at any dose |
Most common AEs: nasopharyngitis and asymptomatic ↑ of aminotransferase levels |
| Tolebrutinib (5 mg, 15 mg, 30 mg, 60 mg) | NCT03889639 [70] | 130 RRMS | Phase II, double-blind, Pbo (16 weeks) |
↓ new/newly enlarging T2-hyperitense lesions vs Pbo at 12 weeks (2.12 with Pbo, 1.90 with 5 mg, 1.32 with 15 mg, 1.30 with 30 mg, 0.23 with 60 mg) ↓ Gd+ lesions vs Pbo at 12 weeks (1.03 with Pbo, 1.39 with 5 mg, 0.77 with 15 mg, 0.76 with 30 mg, 0.13 with 60 mg) |
– | |
| Tolebrutinib (5 mg, 15 mg, 30 mg, 60 mg) | NCT03889639 [71] | 61 RRMS | Phase II, double-blind, Pbo (16 weeks) |
↓ new/newly enlarging T2-hyperitense lesions vs Pbo at 12 weeks (1.44 with Pbo, 1.09 with 5 mg, 0.89 with 15 mg, 0.75 with 30 mg, 0.15 with 60 mg) ↓ Gd+ lesions vs Pbo at 12 weeks (0.89 with Pbo, 0.82 with 5 mg, 0.5 with 15 mg, 0.38 with 30 mg, 0.08 with 60 mg) |
– |
AE adverse events, BTKi Bruton’s tyrosine kinase inhibitors, CDP confirmed disability progression, DMF dymethil fumarate, EDSS expanded Disability Status Scale, Gd+ gadolinium-enhancing, IARs infusion-associated reactions, Pbo placebo, RRMS relapsing–remitting multiple sclerosis, SPMS secondary progressive multiple sclerosis