From: Neuromyelitis optica spectrum disorders: from pathophysiology to therapeutic strategies
Drug | Study design | Study phase/ClinicalTrials.gov Identifier (status 01/2021) | Number of patients (randomization) | NMOSD serostatus | Free of relapses/relapse reduction (RR) | Follow-up | Disability (EDSS stabilization or improvement) | Safety concerns |
---|---|---|---|---|---|---|---|---|
Azathioprine (AZA) | Retrospective studies | Off-label (including meta-analysis) | 977 | AQP4-ab + and - | 34–61% | 18–47 months | Up to 69% during 5 year | GI, infections, Hepatotoxicity Bone marrow suppression Malignancy |
Micophenolate mofetil (MMF) | Retrospective studies | Off-label (including meta-analysis) | 799 | AQP4-ab + and - | 46–73% | 20–27 months | Up to 90% during 5 year | GI, infections, Hepatotoxicity Bone marrow suppression Teratogenicity |
Rituximab (RTX) | Retrospective studies | Off-label (including meta-analysis) | 577 | AQP4-ab + and - | 62.9 (52–88%) | 24–60 months | Up to 97% during 5 year Dif EDSS: -1.16 | Mucocutaneous reactions HBV reactivation Severe hypogammaglobulinemia |
Multi-center, randomized, double-blind, placebo-controlled trial (Japan) | Phase 2,3 study UMIN000013453 | 38 (1:1) | AQP4-ab + | 100% | 72 weeks | Change in EDSS (− 0.26 vs. − 0.32) NSD | NSD compared with placebo | |
Tocilizumab (TCZ) | Single-center randomized, open-label, parallel-group study (TANGO; China) | Phase 2,3 study comparing TCZ vs AZA NCT03350633 | 118 (1:1) | AQP4-ab + and - | TCZ: 92% AZA: 68% RR: NA | 48 weeks 48 weeks | OR = 0.34 | Pneumonia (3%), herpes zoster virus (2%), deep vein thrombosis (2%), basal ganglia haemorrhage (2%) |
Single-center, open-label trial (China) | Phase 1 and 2 study as monotherapy (completed) NCT03062579 | 10 | AQP4-ab + and -* | NA | 1 year | NA | NA | |
Eculizumab | Multicenter, randomized, placebo-controlled, time-to-event trial (PREVENT trial) | Phase 3 study (add-on therapy) NCT01892345 | 143 (2:1) | AQP4-ab + | 96.1% RR:93.1% | 96 weeks | NSD | Increased risk of meningococcal infection. All patients had to receive vaccination 2 weeks prior to first dose |
Inebilizumab | Multi-center, randomized, double-blind, placebo-controlled (N-Momentum) | Phase 2/3 study NCT02200770 | 231 (3:1) | AQP4-ab + and - | 87.6% RR: 73% (77.3% in AQP4-ab+) | 28 weeks | OR = 0.37 | NSD compared to placebo |
Satralizumab | Multicenter, randomized, placebo-controlled, time-to-event trial (SakuraSky) | Phase 3 study (add-on therapy) NCT02028884 | 83 (1:1) | AQP4-ab + and - | AQP4+ 91.5% AQP4-: 56.3% RR:62% (79% in AQP4-ab+) | 96 weeks | NA | NSD compared to placebo |
Multicenter, randomized, placebo-controlled, time-to-event trial (SakuraStar) | Phase 3 study (monotherapy) NCT02073279 | 95 (2:1) | AQP4-ab + and - | AQP4+ 76.5% AQP4-: 63.3% RR:55% (74% in AQP4-ab+) | 96 weeks | NA | NSD compared to placebo | |
Telitacicept | Randomized, placebo-controlled (China) | Phase 3 study (active, recruiting) NCT03330418 | 118 (estimated enrollment) | AQP4-ab + | NA | Time frame: 144 weeks | NA | NA |
Ravulizumab | Multicenter, open-label, external placebo-controlled | Phase 3 study (active, recruiting) NCT04201262 | 55 (estimated enrollment) | AQP4-ab +* | NA | Time frame: 2 years | NA | NA |
Bortezomib | Single-center, Open Label Trial (USA) | Phase 2 add-on study (completed) NCT02893111 | 5 | AQP4-ab+* | NA | Time frame: 1 year | NA | NA |
Cetirizine | Single-center, Open Label Trial (USA) | Phase 2 add-on study (completed) NCT02865018 | 16 | AQP4-ab+ (with ON or TM)** | NA | Time frame: 1 year | NA | NA |
BAT4406F | Single-center, Open Label Trial (China) | Phase 1 dose-escalation study (not yet recruiting) NCT04146285 | 48 (estimated enrollment) | AQP4-ab + and -* | NA | NA | NA | NA |
SHR1459 | Single-center, Open Label Trial (China) | Phase 2 study (not yet recruiting) NCT04670770 | 10 (estimated enrollment) | AQP4-ab +* | NA | Time frame: 52 weeks | NA | NA |
Hematopoietic Stem Cell Transplantation | Single Group Assignment; Open Label study (USA) | Phase 1, 2 study (completed) NCT00787722 | 13 (12 completed the study) | AQP4-ab+ (n=12) and unknown (n=1) | 80% | 5 years | at baseline: 4.4 at FU: 3.3 | 1/13 died due to unrelated complications from SLE Neutropenic fever (5/13), Hypophosphatemia (9/13) Infections (1/13) |