Long-term safety of satralizumab in neuromyelitis optica spectrum disorder (NMOSD) from SAkuraSky and SAkuraStar

Yamamura, Takashi; Weinshenker, Brian G.; Yeaman, Michael R.; Sèze, Jérôme De; Patti, Francesco; Lobo, Patricia; Büdingen, H.-Christian von; Kou, Xiujing; Weber, Kristina; Greenberg, Benjamin

doi:10.1016/j.msard.2022.104025

Cited by 29 publications

(23 citation statements)

References 35 publications

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“…13,14 Long-term safety analyses from the SAkura studies showed that the favorable safety profile and tolerability of satralizumab is sustained with long-term treatment when administered as a monotherapy or in combination with baseline IST. 17 The positive, long-term efficacy results from this study were supported by the strong uptake for the OLE periods, with 103 of 119 AQP4-IgG-seropositive patients (87%) from the double-blind periods transitioning into the OLEs. More than 90% of patients who received satralizumab continued treatment for more than 1 year.…”

Section: Discussionsupporting

confidence: 57%

“…Most AEs in the total satralizumab treatment period were mild or moderate in severity, and there were no reported deaths and no anaphylactic reactions related to satralizumab. 17…”

Section: Resultsmentioning

confidence: 99%

“…A detailed analysis of the long-term safety of satralizumab has been published. 17 Top-line safety results from this analysis have been presented here.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

Kleiter

Traboulsee

Palace

et al. 2023

Neurol Neuroimmunol Neuroinflamm

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Background and ObjectivesSatralizumab, 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.MethodsFollowing 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).ResultsForty-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.DiscussionThese 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 InformationClinicalTrials.gov registration numbers:NCT02028884(SAkuraSky) andNCT02073279(SAkuraStar).Classification of EvidenceThis 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.

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Section: Discussionsupporting

confidence: 57%

“…Most AEs in the total satralizumab treatment period were mild or moderate in severity, and there were no reported deaths and no anaphylactic reactions related to satralizumab. 17…”

Section: Resultsmentioning

confidence: 99%

“…A detailed analysis of the long-term safety of satralizumab has been published. 17 Top-line safety results from this analysis have been presented here.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

Kleiter

Traboulsee

Palace

et al. 2023

Neurol Neuroimmunol Neuroinflamm

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“…In addition, the use of colony-stimulating factor treatment and grade 5 or profound neutropenia were not registered in both Sakura trials; this safety profile is in line with that observed with other IL-6 receptor antagonists, such as tocilizumab, 6 most being mild or moderate in severity throughout the overall satralizumab treatment period (until February 2021). 7 Despite analytic control recommendation of satralizumab is to perform the first exam at 4 weeks, 2,3 reported neutropenia in clinical trials developed after 2 weeks and our patient's symptoms began at week 3, it might be reasonable to request the first analytic control at week 2, to closely monitor neutrophil count and prevent further complications, if necessary. Finally, colony-stimulating factor response should be monitored, since it may be effective in treating neutropenia.…”

Section: Discussionmentioning

confidence: 92%

Severe febrile neutropenia associated with satralizumab in an Argentinian neuromyelitis optica spectrum disorder patient

Pestchanker¹,

Diaconchuk²,

López³

et al. 2022

Mult Scler

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Background: Recently, satralizumab (interleukin-6 receptor blocker) was approved for seropositive neuromyelitis optica spectrum disorder (NMOSD) patients. In SAkuraSky trial, mild neutropenia was reported in 15% of patients under satralizumab. Most neutropenias were transient; grade 3–4 was not related to serious infections. So far, no severe neutropenia (<100 cell/mm3) has been reported worldwide. Methods: We present an aquaporin-4-antibody-positive NMOSD patient who developed severe febrile neutropenia 2 weeks after adding satralizumab to her azathioprine treatment. Conclusion: Analytic control for satralizumab is recommended at 4 weeks. However, we recommend this control at week 2, in order to closely monitor neutrophil count and prevent further complications.

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Update on the diagnosis and treatment of neuromyelitis optica spectrum disorders (NMOSD) – revised recommendations of the Neuromyelitis Optica Study Group (NEMOS). Part II: Attack therapy and long-term management

Kuempfel¹,

Giglhuber²,

Aktaş³

et al. 2023

J Neurol

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This manuscript presents practical recommendations for managing acute attacks and implementing preventive immunotherapies for neuromyelitis optica spectrum disorders (NMOSD), a rare autoimmune disease that causes severe inflammation in the central nervous system (CNS), primarily affecting the optic nerves, spinal cord, and brainstem. The pillars of NMOSD therapy are attack treatment and attack prevention to minimize the accrual of neurological disability. Aquaporin-4 immunoglobulin G antibodies (AQP4-IgG) are a diagnostic marker of the disease and play a significant role in its pathogenicity. Recent advances in understanding NMOSD have led to the development of new therapies and the completion of randomized controlled trials. Four preventive immunotherapies have now been approved for AQP4-IgG-positive NMOSD in many regions of the world: eculizumab, ravulizumab - most recently-, inebilizumab, and satralizumab. These new drugs may potentially substitute rituximab and classical immunosuppressive therapies, which were as yet the mainstay of treatment for both, AQP4-IgG-positive and -negative NMOSD. Here, the Neuromyelitis Optica Study Group (NEMOS) provides an overview of the current state of knowledge on NMOSD treatments and offers statements and practical recommendations on the therapy management and use of all available immunotherapies for this disease. Unmet needs and AQP4-IgG-negative NMOSD are also discussed. The recommendations were developed using a Delphi-based consensus method among the core author group and at expert discussions at NEMOS meetings.

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Long-term safety of satralizumab in neuromyelitis optica spectrum disorder (NMOSD) from SAkuraSky and SAkuraStar

Cited by 29 publications

References 35 publications

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

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

Severe febrile neutropenia associated with satralizumab in an Argentinian neuromyelitis optica spectrum disorder patient

Update on the diagnosis and treatment of neuromyelitis optica spectrum disorders (NMOSD) – revised recommendations of the Neuromyelitis Optica Study Group (NEMOS). Part II: Attack therapy and long-term management

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