Dados do Trabalho

Título

Safety and efficacy of inebilizumab in NMOSD over a mean treatment duration of 3.2 years: end of study data from the N-MOmentum trial

Resumo

Introduction:
Inebilizumab is approved in the USA and Japan for aquaporin 4 immunoglobulin (Ig)G
seropositive neuromyelitis optica spectrum disorder (NMOSD).
Objective:
To report final safety and efficacy data from the N-MOmentum trial of inebilizumab in NMOSD.
Methods:
Participants with NMOSD (aged 18+, EDSS score of ≤8, recent history of attacks) were
randomized 3:1 to inebilizumab or placebo monotherapy for 28 weeks or up to attack
occurrence; the randomized controlled period (RCP). Primary outcome was time to
adjudicated attack. Participants could then enter the inebilizumab open label period (OLP).
Final study data are presented, including attack risk and safety outcomes.
Results
Of the 230 participants randomized and dosed, 216 (93.9%) entered and 174 (80.6%)
completed the OLP. In the RCP, 87.0% were attack free with inebilizumab and 59.9% with
placebo (72.8% risk reduction, p<0.001). In the OLP, 87.7% were attack-free in those
continuing inebilizumab and 83.4% in those switched from placebo.
Regardless of randomization, 225 participants received inebilizumab. Mean (SD) treatment
duration was 3.2 (1.4) years; 36.8% were treated for >4 years (maximum of 5.5 years). Total
exposure was 730.36 person-years (py) with an annualized attack rate of 0.092; 40/63
(63.5%) attacks occurred in the first year.
Treatment-emergent adverse events (AE) were reported by 89 (39.6%) participants, most
frequently urinary tract infection (26.2%), nasopharyngitis (20.9%) and arthralgia (17.3%).
Infusion-related reactions with inebilizumab occurred in 28 (12.9%) participants (rate per
100-py: whole study, 11.1; RCP, 37.6). The rate (95% confidence interval) of infections per
100-py did not increase with continued treatment: year 1, 116.3 (102.4-131.6); year 2, 68.1
(57.2-80.6); year 3, 61.9 (50.3-75.5); year 4, 55.1 (41.7-71.4). 105 participants had
transient low IgG (<700 mg/dL) during treatment, but no correlations were found between
the worst IgG, IgM or IgA levels recorded and the occurrence of any infection or an infection
grade 3 (Fisher exact test, all p>0.05). Three trial participants died: one from complications
of NMOSD attack, one from a CNS event of unclear etiology and one due to COVID-19, after
9, 224 and 1225 days of inebilizumab treatment, respectively.
Conclusions
During the 5.5 years of N-MOmentum, the risk of attack in participants receiving
inebilizumab remained low with no evidence of unexpected serious adverse events,
including serious infection.

Palavras Chave

NMOSD ; Inebilizumab ; aquaporin-4 ; anti-AQP-4

Área

Neuroimunologia