RT Journal Article
SR Electronic
T1 Long-term Efficacy of Satralizumab in AQP4-IgG–Seropositive Neuromyelitis Optica Spectrum Disorder From SAkuraSky and SAkuraStar
JF Neurology - Neuroimmunology Neuroinflammation
JO Neurol Neuroimmunol Neuroinflamm
FD Lippincott Williams & Wilkins
SP e200071
DO 10.1212/NXI.0000000000200071
VO 10
IS 1
A1 Ingo Kleiter
A1 Anthony Traboulsee
A1 Jacqueline Palace
A1 Takashi Yamamura
A1 Kazuo Fujihara
A1 Albert Saiz
A1 Adil Javed
A1 David Mayes
A1 H-Christian von Büdingen
A1 Gaelle Klingelschmitt
A1 Daniela Stokmaier
A1 Jeffrey L. Bennett
YR 2023
UL http://nn.neurology.org/content/10/1/e200071.abstract
AB Background and Objectives Satralizumab, an interleukin 6 receptor inhibitor, reduced the risk of protocol-defined relapse (PDR) vs placebo in 2 independent, double-blind studies in patients with neuromyelitis optica spectrum disorder (NMOSD). We assessed the long-term efficacy of satralizumab in patients with aquaporin-4-immunoglobulin G (IgG)–seropositive (AQP4-IgG+) NMOSD.Methods Following the double-blind periods of SAkuraSky (satralizumab + baseline immunosuppressive treatment [IST]) and SAkuraStar (satralizumab monotherapy), patients could enter the open-label extension (OLE, satralizumab 120 mg Q4W ± IST). This analysis included all AQP4-IgG+ patients who received ≥1 dose of satralizumab in the double-blind and/or OLE periods, from patients' first dose to the data cutoff (February 22, 2021). PDR in the OLE period was determined by the investigator without external adjudication. We evaluated time to first investigator-reported PDR (iPDR), severe iPDR (≥2 point increase in the Expanded Disability Status Scale [EDSS] score), and sustained EDSS worsening (EDSS score increase of ≥2, ≥1, or ≥0.5 points for patients with baseline scores of 0, 1–5, or ≥5.5, respectively, confirmed ≥24 weeks post–initial worsening), plus the annualized iPDR rate (ARR).Results Forty-six of 55 AQP4-IgG+ patients (84%) in SAkuraSky and 57/64 patients in SAkuraStar (89%) continued from the double-blind periods into the OLEs. In total, 111 AQP4-IgG+ patients received ≥1 dose of satralizumab in the double-blind and/or OLE periods and were included in these analyses (SAkuraSky: 49; SAkuraStar: 62). The median (range) duration of satralizumab exposure was 4.4 (0.1–7.0) years in SAkuraSky and 4.0 (0.1–6.0) years in SAkuraStar, with a combined 440.1 patient-years of treatment. Seventy-one of 111 patients (64%) received satralizumab for ≥192 weeks (3.7 years). At this time point, 71% (SAkuraSky) and 73% (SAkuraStar) of satralizumab-treated patients were free from iPDR, 91% (SAkuraSky) and 90% (SAkuraStar) were free from severe iPDR, and 90% (SAkuraSky) and 86% (SAkuraStar) had no sustained EDSS worsening. The overall adjusted ARR (95% CI) was 0.12 (0.08–0.18) in SAkuraSky and 0.08 (0.05–0.13) in SAkuraStar and remained stable over time.Discussion These long-term results from the OLE periods of the SAkura studies demonstrate the continued efficacy of satralizumab over more than 3.5 years of treatment. High proportions of patients remained free from relapse, severe relapse, or worsening disease, with a consistently low ARR.Trial Registration Information ClinicalTrials.gov registration numbers: NCT02028884 (SAkuraSky) and NCT02073279 (SAkuraStar).Classification of Evidence This study provides Class II evidence that satralizumab reduces the risk of relapse in patients with AQP4-IgG+ NMOSD beyond the first 96 weeks of treatment.ARR=annualized iPDR rate; AQP4-IgG+=aquaporin-4–immunoglobulin G seropositive; AZA=azathioprine; CEC=Clinical Endpoint Committee; EDSS=Expanded Disability Status Scale; HR=hazard ratio; IL-6=interleukin 6; iPDR=investigator-reported protocol-defined relapse; IST=immunosuppressive treatment; MMF=mycophenolate mofetil; NMOSD=neuromyelitis optica spectrum disorder; OCS=oral corticosteroid; OLE=open-label extension; PDR=protocol-defined relapse; PY=patient-year