SAT0117 Sarilumab, a Subcutaneously-Administered, Fully-Human Monoclonal Antibody Inhibitor of The IL-6 Receptor: Relationship Between Eular Responses and Change from Baseline of Selected Clinical Parameters

Genovese, M. C.; Fleischmann, R; Fiore, Stefano; Radin, Allen; Fan, Chunpeng; Huizinga, T.W.J.

doi:10.1136/annrheumdis-2013-eular.1843

Cited by 10 publications

(6 citation statements)

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“… 74 Preclinical data on SAR demonstrated a dose-dependent inhibition of IL-6 signaling with lower concentration than tocilizumab and with no evidence of complement-dependent or antibody-dependent cell-mediated cytotoxicity. 75 , 76 Efficacy and safety profiles of sarilumab were tested in clinical trials for treatment of patients with active RA, who were unresponsive or intolerant to either previous MTX or TNFi, as described in detail in the following sections in this review. To date, other IL-6 blocking agents are currently under investigation in clinical trials for the treatment of rheumatic diseases.…”

Section: Introductionmentioning

confidence: 99%

Profile of sarilumab and its potential in the treatment of rheumatoid arthritis

Raimondo

Biggioggero

Crotti

et al. 2017

DDDT

103

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In recent years the use of biotechnological agents has drastically revolutionized the therapeutic approach and the progression of rheumatoid arthritis (RA). In particular, interleukin-6 (IL-6) has been demonstrated as a pivotal cytokine in the pathogenesis of the disease by contributing to both the innate and the adaptive immune system perturbation, and to the production of acute-phase proteins involved in the systemic expression of the disorder. The first marketed IL-6 blocker was tocilizumab, a humanized anti-IL-6 receptor (anti-IL-6R) monoclonal antibody. The successful use of tocilizumab in RA has encouraged the development of other biologic agents specifically targeting the IL-6 pathway, either directed against IL-6 cytokine (sirukumab, olokizumab, and clazakizumab) or IL-6 receptor (sarilumab). One Phase II and six Phase III randomized controlled trials demonstrated a broad efficacy of sarilumab across all RA patient subtypes, ranging from methotrexate (MTX) to tumor necrosis factor inhibitor insufficient responders. In particular, sarilumab as monotherapy demonstrated a clear head-to-head superiority over adalimumab in MTX-intolerant subjects. In addition, compared with tocilizumab, sarilumab showed a similar safety profile with significantly higher affinity and longer half-life, responsible for a reduction of the frequency of administration (every other week instead weekly). All these aspects may be important in defining the strategy for positioning sarilumab in the treatment algorithm of RA. Indeed, observational data coming from post-marketing real-life studies may provide crucial additional information for better understanding the role of sarilumab in the management of the disease. This review summarizes both the biological role of IL-6 in RA and the clinical data available on sarilumab as an alternative therapeutic option in RA patients.

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Section: Introductionmentioning

confidence: 99%

Profile of sarilumab and its potential in the treatment of rheumatoid arthritis

Raimondo

Biggioggero

Crotti

et al. 2017

DDDT

103

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“…Sarilumab (SAR153191/REGN88) is a fully human anti-IL-6Rα mAb that binds membrane-bound and soluble human IL-6Rα with high affinity thereby blocking cis and trans IL-6-mediated inflammatory signalling cascade, and with no evidence of complement-dependent or antibody-dependent cell-mediated cytotoxicity. 20 Sarilumab has been shown in preclinical studies to inhibit IL-6 signalling in a dose-dependent manner. 21–23 In Phase I studies subcutaneous sarilumab was generally well tolerated and, in patients with RA, 24 25 reduced acute phase reactants including C reactive protein (CRP).…”

Section: Introductionmentioning

confidence: 99%

Sarilumab, a fully human monoclonal antibody against IL-6Rα in patients with rheumatoid arthritis and an inadequate response to methotrexate: efficacy and safety results from the randomised SARIL-RA-MOBILITY Part A trial

Huizinga

Fleischmann

Jasson

et al. 2014

Annals of the Rheumatic Diseases

185

132

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ObjectivesTo evaluate safety and efficacy of weekly (qw) and every other week (q2w) dosing of sarilumab, a fully human anti-interleukin 6 receptor α (anti-IL-6Rα) monoclonal antibody, for moderate-to-severe rheumatoid arthritis (RA).MethodsIn this dose-ranging study, patients (n=306) with active RA, despite methotrexate, were randomly assigned to placebo or one of five subcutaneous doses/regimens of sarilumab: 100 mg q2w, 150 mg q2w, 100 mg qw, 200 mg q2w, 150 mg qw for 12 weeks, plus methotrexate. The primary end point was ACR20 at Week 12. Secondary endpoints included ACR50, ACR70, Disease Activity Score in 28 joints (C reactive protein). Safety, pharmacokinetics, pharmacodynamics and efficacy in population subgroups were assessed.ResultsThe proportion of patients achieving an ACR20 response compared with placebo was significantly higher for sarilumab 150 mg qw (72.0% vs 46.2%, multiplicity adjusted p=0.0203). Higher ACR20 responses were also attained with 150 mg q2w (67%; unadjusted (nominal) p=0.0363) and 200 mg q2w (65%; unadjusted p=0.0426) versus placebo. Sarilumab ≥150 mg q2w reduced C reactive protein, which did not return to baseline between dosing intervals. Infections were the most common adverse event; none were serious. Changes in laboratory values (neutropenia, transaminases and lipids) were consistent with reports with other IL-6Rα inhibitors.ConclusionsSarilumab improved signs and symptoms of RA over 12 weeks in patients with moderate-to-severe RA with a safety profile similar to reports with other IL-6 inhibitors. Sarilumab 150 mg and sarilumab 200 mg q2w had the most favourable efficacy, safety and dosing convenience and are being further evaluated in Phase III.

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“…Information on the pharmacodynamics of sarilumab were collected from abstracts, the package insert, product information provided to the FDA, published research, introductory sections in the published clinical studies, and other reviews. 9,[15][16][17][18][19][20][21][22] Each author took primary responsibility for the extraction and inclusion of information within a specific section of the article and then reviewed all other sections to ensure accuracy and completeness.…”

Section: Methodsmentioning

confidence: 99%