Macrophage Activation Syndrome in Patients with Systemic Juvenile Idiopathic Arthritis under Treatment with Tocilizumab

Yokota, Shumpei; Itoh, Yasuhiko; Morio, Tomohiro; Sumitomo, Naokata; Daimaru, Kaori; Minota, Seiji

doi:10.3899/jrheum.140288

Cited by 93 publications

(59 citation statements)

References 37 publications

(30 reference statements)

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“…The results we obtained in the current study would indicate there may be a role for tocilizumab in controlling secondary HLH/MAS. Interestingly, a study of tocilizumab for patients with SoJIA observed the appearance of MAS in approximately 4% of the cohort, similar to the reported frequency of MAS found in SoJIA patients not receiving tocilizumab (59,60). Similarly, SoJIA patients treated with other biologic therapies including canakinumab, etanercept, and anakinra showed a low frequency of MAS development while on therapy, indicating that single cytokine inhibition may not be sufficient to prevent the development of MAS.…”

Section: Discussionmentioning

confidence: 62%

A xenograft model of macrophage activation syndrome amenable to anti-CD33 and anti–IL-6R treatment

Wunderlich¹,

Stockman²,

Devarajan³

et al. 2016

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Section: Discussionmentioning

confidence: 62%

A xenograft model of macrophage activation syndrome amenable to anti-CD33 and anti–IL-6R treatment

Wunderlich¹,

Stockman²,

Devarajan³

et al. 2016

JCI Insight

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“…An independent adjudication committee examined all cases reported as MAS by investigators, as well as all cases of increased transaminases, in a phase III clinical trial of tocilizumab in sJIA performed in Europe, Australia and the USA (112 patients, 403 patient-years of exposure), in a separate sJIA phase III trial (149 patients, 326 patient-years), and in a post-marketing surveillance program in Japan (366 patients, 524 patient-years) 16,65,66 . In total, 22 events were adjudicated as definite ( n = 11) or potential ( n = 11) MAS in 21 (3.3%) of the 627 patients with sJIA included in the entire database (see Supplementary information S1 (table) for criteria).…”

Section: Effects Of Biologic Therapy On Masmentioning

confidence: 99%

“…Moreover, these episodes also seemed to present less commonly with hepatomegaly. In almost three-quarters of all cases, C-reactive protein (CRP) levels remained within the normal range 16,66 . Given the role of IL-6 in inducing the acute-phase response of the liver, this observation is not unexpected.…”

Section: Effects Of Biologic Therapy On Masmentioning

confidence: 99%

Macrophage activation syndrome in the era of biologic therapy

2016

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Macrophage activation syndrome (MAS) refers to acute overwhelming inflammation caused by a ‘cytokine storm’. Although increasingly recognized as a life-threatening complication of various rheumatic diseases, clinically, MAS is strikingly similar to primary and secondary forms of haemophagocytic lymphohistiocytosis (HLH). Not surprisingly, many rheumatologists prefer the term secondary HLH rather than MAS to describe this condition, and efforts to change the nomenclature are in progress. The pathophysiology of MAS remains elusive, but observations in animal models, as well as data on the effects of new anticytokine therapies on rates and clinical presentations of MAS in patients with systemic juvenile idiopathic arthritis (sJIA), provide clues to the understanding of this perplexing clinical phenomenon. In this Review, we explore the latest available evidence and discuss potential diagnostic challenges in the era of increasing use of biologic therapies.

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“…One of SJIA complications is Macrophage-Activating Syndrome (MAS), a life threatening disease, associated with impaired bone-marrow and liver functions. Tocilizumab treatment does not prevent or worsen MAS [112]; however, it does mask the clinical symptoms, again by reducing the CRP levels, which allow diagnosing the outbreak of this syndrome [113]. Blocking IL-1 with anakinra, on the other hand, was shown to reduce MAS severity in SJIA patients [114–116].…”

Section: Anti-inflammatory Cytokine Biologicsmentioning

confidence: 99%

Biologics for Targeting Inflammatory Cytokines, Clinical Uses, and Limitations

Rider

Carmi

Bar‐Sela

2016

International Journal of Cell Biology

169

111

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Proinflammatory cytokines are potent mediators of numerous biological processes and are tightly regulated in the body. Chronic uncontrolled levels of such cytokines can initiate and derive many pathologies, including incidences of autoimmunity and cancer. Therefore, therapies that regulate the activity of inflammatory cytokines, either by supplementation of anti-inflammatory recombinant cytokines or by neutralizing them by using blocking antibodies, have been extensively used over the past decades. Over the past few years, new innovative biological agents for blocking and regulating cytokine activities have emerged. Here, we review some of the most recent approaches of cytokine targeting, focusing on anti-TNF antibodies or recombinant TNF decoy receptor, recombinant IL-1 receptor antagonist (IL-1Ra) and anti-IL-1 antibodies, anti-IL-6 receptor antibodies, and TH17 targeting antibodies. We discuss their effects as biologic drugs, as evaluated in numerous clinical trials, and highlight their therapeutic potential as well as emphasize their inherent limitations and clinical risks. We suggest that while systemic blocking of proinflammatory cytokines using biological agents can ameliorate disease pathogenesis and progression, it may also abrogate the hosts defense against infections. Moreover, we outline the rational need to develop new therapies, which block inflammatory cytokines only at sites of inflammation, while enabling their function systemically.

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Macrophage Activation Syndrome in Patients with Systemic Juvenile Idiopathic Arthritis under Treatment with Tocilizumab

Abstract: These results suggest that the clinical/laboratory features in the course of MAS appear to be similar among patients regardless of whether TCZ is administered. Similarities in the pathophysiological background of MAS and EB-VAHS were also suggested.

Cited by 93 publications

References 37 publications

A xenograft model of macrophage activation syndrome amenable to anti-CD33 and anti–IL-6R treatment

A xenograft model of macrophage activation syndrome amenable to anti-CD33 and anti–IL-6R treatment

Macrophage activation syndrome in the era of biologic therapy

Biologics for Targeting Inflammatory Cytokines, Clinical Uses, and Limitations

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