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Table 3 Therapeutic options for long-term relapse prevention in NMOSD

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)

  1. AQP4-ab + positive aquaporin-4 antibodies, NMOSD neuromyelitis optica spectrum disorders, EDSS Expanded disability Status Scale, NSD no statistical differences, USA United States of America, NA not available, ON optic neuritis, TM transverse myelitis, SLE systemic lupus erythematosus, GI gastrointestinal
  2. *Participants must have AQP4-ab + and a diagnosis of NMOSD as defined by the 2015 International Consensus Diagnostic Criteria. ** Diagnosis of NMOSD as defined by the 2006 Revised NMO Diagnostic Criteria