Safety and efficacy of satralizumab monotherapy in neuromyelitis optica spectrum disorder: a randomised, double-blind, multicentre, placebo-controlled phase 3 trial

Traboulsee, Anthony; Greenberg, Benjamin; Bennett, Jeffrey L.; Szczechowski, L; Fox, Edward J.; Shkrobot, Svitlana; Yamamura, Takashi; Terada, Yayoi; Kawata, Yuichi; Wright, Pádraig; Gianella‐Borradori, Athos; Garren, Hideki; Weinshenker, Brian G.

doi:10.1016/s1474-4422(20)30078-8

Cited by 331 publications

(372 citation statements)

References 27 publications

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“…The proportion of relapse-free patients in the satralizumab and placebo groups was 89% versus 66% at week 48, 78% versus 59% at week 96 and 74% versus 49% at week 144, respectively [27]. There was no significant difference between satralizumab and placebo groups in the predefined key secondary outcomes, change in Visual Analogue Scale pain score and the Functional Assessment of Chronic Illness Therapy (FACIT) fatigue score from baseline to week 24 [26,27].…”

Section: Therapeutic Trialsmentioning

confidence: 90%

“…Moreover, subcutaneous satralizumab significantly inhibited IL-6 receptor signalling for four weeks, with marked, sustained increases in soluble IL-6 receptor levels observed in Japanese and Caucasian healthy volunteers (n = 72) and patients with rheumatoid arthritis (n = 33) or with NMOSD (n = 104) [25]. In NMOSD patients who received subcutaneous satralizumab 120 mg at week 0, 2, 4 (loading regimen) and once every 4 weeks thereafter (maintenance regimen), the predicted median IL-6 receptor occupancy was maintained at > 95% over the satralizumab 4-week dosing interval [25][26][27]. Decreases in C-reactive protein, fibrinogen and complement (C3, C4 and CH50) were also observed with satralizumab treatment [16].…”

Section: Pharmacodynamicsmentioning

confidence: 99%

“…In SAkuraSky, baseline immunosuppressant therapy included azathioprine (AZA), mycophenolate mofetil (MMF) or oral corticosteroids at stable doses, with adolescent patients permitted to receive a combination of AZA and oral corticosteroids, or MMF and oral corticosteroids [27]. Patients experiencing a protocol-defined relapse (PDR) or those completing the double-blind period of the study were eligible to enter an open-label extension period, during which all patients received unblinded long-term treatment with satralizumab [26,27]. During the double-blind period, satralizumab was effective in reducing the risk of an adjudicated NMOSD relapse whether it was administered as a monotherapy or as an addon therapy to baseline immunosuppressant therapy [26,27].…”

Section: Therapeutic Trialsmentioning

confidence: 99%

“…Patients experiencing a protocol-defined relapse (PDR) or those completing the double-blind period of the study were eligible to enter an open-label extension period, during which all patients received unblinded long-term treatment with satralizumab [26,27]. During the double-blind period, satralizumab was effective in reducing the risk of an adjudicated NMOSD relapse whether it was administered as a monotherapy or as an addon therapy to baseline immunosuppressant therapy [26,27]. In SAkuraStar (median treatment duration: 92.3 weeks with satralizumab vs 54.6 weeks with placebo), the proportion of patients experiencing a PDR was significantly (p = 0.018) lower in the satralizumab monotherapy group than in the placebo group (30% vs 50%), with satralizumab reducing the risk of relapse by 55% [hazard ratio (HR) 0.45, 95% CI 0.23-0.89; primary endpoint in the intention-to-treat population, encompassing both AQP4-IgG seropositive and seronegative subgroups] [26].…”

Section: Therapeutic Trialsmentioning

confidence: 99%

“…In SAkuraStar (median treatment duration: 92.3 weeks with satralizumab vs 54.6 weeks with placebo), the proportion of patients experiencing a PDR was significantly (p = 0.018) lower in the satralizumab monotherapy group than in the placebo group (30% vs 50%), with satralizumab reducing the risk of relapse by 55% [hazard ratio (HR) 0.45, 95% CI 0.23-0.89; primary endpoint in the intention-to-treat population, encompassing both AQP4-IgG seropositive and seronegative subgroups] [26]. The proportion of relapse-free patients in the satralizumab and placebo groups was 76% versus 62% at week 48, 72% versus 51% at week 96 and 63% versus 34% at week 144, respectively [26]. Similarly, in SAkuraSky (median treatment duration: 107.4 weeks with satralizumab vs 32.5 weeks with placebo), a significantly (p = 0.02) lower proportion of patients receiving add-on satralizumab experienced a PDR than those receiving placebo (20% vs 43%), with satralizumab reducing the risk of relapse by 62% (HR 0.38, 95% CI 0.16-0.88; primary endpoint in the intention-to-treat population, encompassing both AQP4-IgG seropositive and seronegative subgroups) [27].…”

Section: Therapeutic Trialsmentioning

confidence: 99%

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Satralizumab: First Approval

Heo

2020

Drugs

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Satralizumab (Enspryng ®), a humanized anti-interleukin-6 (IL-6) receptor monoclonal recycling antibody, has been developed by Chugai Pharmaceutical and Roche for the treatment of neuromyelitis optica spectrum disorder (NMOSD). In June 2020, based on positive results from two pivotal phase III trials, subcutaneous satralizumab received its first global approval in Canada for the treatment of NMOSD in adults and children aged ≥ 12 years who are aquaporin 4 water channel autoantibody (AQP4-IgG) seropositive. Satralizumab was subsequently approved in Japan, Switzerland and the USA. Satralizumab is under regulatory review in the EU, and is undergoing clinical development in several countries worldwide. This article summarizes the milestones in the development of satralizumab leading to this first approval for the treatment of NMOSD.

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Section: Therapeutic Trialsmentioning

confidence: 90%

Section: Pharmacodynamicsmentioning

confidence: 99%

Section: Therapeutic Trialsmentioning

confidence: 99%

Section: Therapeutic Trialsmentioning

confidence: 99%

Section: Therapeutic Trialsmentioning

confidence: 99%

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Satralizumab: First Approval

Heo

2020

Drugs

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A meta‐analysis comparing first‐line immunosuppressants in neuromyelitis optica

Giovannelli¹,

Ciron

Cohen³

et al. 2021

Ann Clin Transl Neurol

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Objective As phase III trials have shown interest in innovative but expensive drugs in the treatment of neuromyelitis optica spectrum disorder (NMOSD), data are needed to clarify strategies in the treatment of neuromyelitis optica (NMO). This meta‐analysis compares the efficacy of first‐line strategies using rituximab (RTX), mycophenolate mofetil (MMF), or azathioprine (AZA), which are still widely used. Methods Studies identified by the systematic review of Huang et al. (2019) were selected if they considered at least two first‐line immunosuppressants among RTX, MMF, and AZA. We updated this review. The Medline, Cochrane Central Register of Controlled Trials, Embase, and ClinicalTrials databases were queried between November 2018 and April 2020. To be included, the hazard ratio (HR) [95% CI] for the time to first relapse after first‐line immunosuppression had to be available, calculable, or provided by the authors. Results We gathered data from 919 NMO patients (232 RTX‐, 294 MMF‐, and 393 AZA‐treated patients). The risk of first relapse after first‐line immunosuppression was 1.55 [1.04, 2.31] (p = 0.03) for MMF compared with RTX, 1.42 [0.87, 2.30] (p = 0.16) for AZA compared with RTX, and 0.94 [0.58, 1.54] (p = 0.08) for MMF compared with AZA. Interpretation The findings suggest that RTX is more efficient than MMF as a first‐line therapy. Even if the results of our meta‐analysis cannot conclude that RTX has a better efficacy in delaying the first relapse than AZA, the observed effect difference between both treatments combined with the results of previous studies using as outcome the annualized relapse rate may be in favor of RTX.

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Role of Serum IL‐6 in Neuropsychiatric Systemic lupus Erythematosus

Hirohata

Kikuchi

2021

ACR Open Rheumatology

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Objective The present study was designed in order to elucidate the roles of serum interleukin 6 (IL‐6) in the pathogenesis in neuropsychiatric systemic lupus erythematosus (NPSLE). Methods Paired serum and cerebrospinal fluid (CSF) samples were obtained from 101 patients with SLE when they presented active neuropsychiatric manifestations (69 patients with diffuse psychiatric/neuropsychological syndromes [diffuse NPSLE] and 32 patients with neurologic syndromes or peripheral nervous system involvement [focal NPSLE]) and from 22 control patients without SLE with noninflammatory neurological diseases. The levels of albumin and IL‐6 in CSF and sera were measured by enzyme‐linked immunosorbent assay. Results Serum IL‐6 and CSF IL‐6 were elevated in NPSLE compared with non‐SLE controls. Among NPSLE, serum IL‐6 and CSF IL‐6 were significantly elevated in acute confusional state (ACS) compared with non‐ACS diffuse NPSLE (anxiety disorder, cognitive dysfunction, mood disorder, and psychosis) or focal NPSLE. Q albumin (CSF/serum albumin quotient) was also significantly higher in ACS than in the other two groups of NPSLE. Of note, serum IL‐6 (r = 0.2801, p = 0.0207), but not CSF IL‐6 (r = 0.1602, p = 0.1918), was significantly correlated with Q albumin in patients with diffuse NPSLE, including ACS and non‐ACS. Conclusion These results indicate that serum IL‐6 as well as CSF IL‐6 is involved in the pathogenesis of NPSLE. Moreover, it is suggested that serum IL‐6 might play a most important role in blood‐brain barrier breakdown in NPSLE.

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Safety and efficacy of satralizumab monotherapy in neuromyelitis optica spectrum disorder: a randomised, double-blind, multicentre, placebo-controlled phase 3 trial

Cited by 331 publications

References 27 publications

Satralizumab: First Approval

Satralizumab: First Approval

A meta‐analysis comparing first‐line immunosuppressants in neuromyelitis optica

Role of Serum IL‐6 in Neuropsychiatric Systemic lupus Erythematosus

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