Table 2.
Main data of randomized, double-blind, placebo-controlled, time-to-event trials in NMOSD
| Drug | Trial/Randomization | Number of patients / AQP4-IgG serostatus | Inclusion criteria | Concomitant immuno-suppression | Attacks n (%) (HR, 95% CI, and/or p) | previous immunotherapies | Duration of treatment in core study/open-label extension | |
|---|---|---|---|---|---|---|---|---|
| Previous disease activity | Age [years] | |||||||
| Rituximab | RIN-11/1:1 | 38 / all positive; including 11 AQP4-IgG negative patients who previously tested positive | Any history of optic neuritis or myelitis | 16–80 | No, but oral glucocorticoids, tapered during initiation period | 0 vs. 7 (37%); (p = 0.0058) | 0% with rituximab, other n.a | Median 72.1 weeks/mean 20.5 months (SD 10.1)7 |
| Inebilizumab | N-MOmentum2/3:1 | 230 / 213-positive, 17-negative | ≥ 1 attack in 12 months or ≥ 2 attacks in 24 months | > 18 | No, but oral glucocorticoids during initiation period (20 mg/d until d14, then tapered to d21) | 21 (12%) vs. 22 (39%);(0.272, 0.15–0.496, p < 0.0001) | Inebilizumab group: 66% (mostly azathioprine and glucocorticoids, including 7% with rituximab) | Up to 28 weeks/mean 3.2 years, up to 4.5 years (median)8 |
| Eculizumab | PREVENT3/2:1 | 143 / all-positive | ≥ 2 attacks in 12 months or ≥ 3 attacks in 24 months with 1 attack in the last 12 months | > 18 | Yes | 3 (3%) vs. 20 (43%); (0.06, 0.02–0.20, p < 0.001) | Eculizumab group: 78% IS at baseline; (27% with previous rituximab) | Median 89.4 weeks/median 132 weeks, up to 277 weeks9 |
| Ravulizumab | CHAMPION–NMOSD4/Placebo group of PREVENT as external comparator | 58 / all-positive | ≥ 2 attacks in 12 months or ≥ 3 attacks in 24 months with 1 attack in the last 12 months | > 18 | Yes | 0 vs. 29 (43%) in PREVENT (0.014, 0.000–0.103, p < 0.0001) | Ravulizumab group: 48% IS at baseline; 86% previuos IS (including 36% with previous rituximab) | Median 73.5 weeks (range 11.0–117.7)/OLE ongoing |
| Satralizumab | SAkuraSky5/1:1 | 83 /55 -positive, 28-negative | ≥ 2 attacks in 24 months with 1 attack in the last 12 months | 12–74 | Yes | 8 (20%) vs. 18 (43%); (0.38, 0.16–0.88, p = 0.02) | Satralizumab group: 78% with previous IS before add-on IS at baseline (including 4,9% with rituximab); | Median 107.4 weeks/median 4.4 years (range 0.1–7.0)10 |
| SAkuraStar6/2:1 | 95/63-positive, 31-negative | ≥ 1 attack in 12 months | 18–74 | No | 19 (30%) vs. 16 (50%); (0.45, 0.23–0.89, p = 0.018) | Satralizumab group: 87% with previous IS or other; 13% with previous B-cell depleting therapies | Median 92.3 weeks/median 4.0 years (range 0.1–6.1)10 | |
n.a. not available, HR hazard ratio, CI confidence interval, d day, OLE open-label extension, SD standard deviation, IS immunosuppressive therapy
1Tahara 2020 The Lancet Neurology [216]
2Cree 2019 The Lancet [51]
3Pittock 2019 N Eng J Med [179]
4Pittock 2023 Ann Neurol [178]
5Yamamura 2019 N Eng J Med [250]
6Traboulsee 2020 The Lancet Neurol [223]
7Tahara 2022 MSRD [217]
8Rensel 2022 MSJ [188]
9 Wingerchuk 2021 Ann Neurol [246]
10Yamamura 2022 MSRD [251]