Long-term Efficacy of Satralizumab in AQP4-IgG-Seropositive Neuromyelitis Optica Spectrum Disorder From SAkuraSky and SAkuraStar

Abstract

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.

Figure 1. Flowchart of AQP4-IgG Seropositive Patients in the SAkura Studies

*One patient joined directly into the OLE and remained in the trial at the cutoff for the current analysis (February 22, 2021). Where patients withdrew consent, this applied to all data collection from that point onward, not prior. AQP4-IgG = aquaporin-4-immunoglobulin G; CCOD = clinical cutoff date; DB = double-blind; OLE = open-label extension; R = randomization.

Figure 2. Kaplan-Meier Analysis of Time to First iPDR in the Total Satralizumab Treatment Periods of (A) SAkuraSky and (B) SAkuraStar

PBO = placebo; SAT = satralizumab.

Figure 3. Swim Plot of iPDR Events in All Patients Who Received Satralizumab in SAkuraSky and SAkuraStar

iPDR = investigator-reported protocol-defined relapse.

Figure 4. Kaplan-Meier Analysis of Time to First Severe iPDR in the Total Satralizumab Treatment Periods of (A) SAkuraSky and (B) SAkuraStar

iPDR = investigator-reported protocol-defined relapse; PBO = placebo; SAT = satralizumab.

Figure 5. Kaplan-Meier Analysis of Time to First Sustained EDSS Worsening in the Total Satralizumab Treatment Periods of (A) SAkuraSky and (B) SAkuraStar

EDSS = Expanded Disability Status Scale; PBO = placebo; SAT = satralizumab.