Efficacy of tocilizumab in Takayasu arteritis: Multicenter retrospective study of 46 patients

Mékinian, A.; Resche‐Rigon, M.; Comarmond, Cloé; Soriano, Alessandra; Constans, J.; Alric, Laurent; Jégo, Patrick; Busato, Florian; Cabon, M.; Dhôte, Robin; Lazaro, Estibaliz; Koné‐Paut, Isabelle; Landron, C.; Lavigne, Christian; Lioger, Bertrand; Michaud, Martin; Ruivard, M.; Sacré, Karim; Gottenberg, Jacques Éric; Gaches, F.; Goulenok, Tiphaine; Salvarani, Carlo; Cacoub, P.; Fain, Olivier; Saadoun, David

doi:10.1016/j.jaut.2018.04.002

Cited by 69 publications

(72 citation statements)

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“…A multicenter study of 75 patients with AOSD treated with TCZ or anakinra also reported similar improvements in clinical manifestations (fever, articular, rash, and lymphadenopathy) over 12 months of therapy between the two study treatments, although improvements in CRP and ESR levels appeared to be greater with TCZ than with anakinra [89]. Furthermore, the preliminary results of a small, prospective, single-arm pilot study in eight patients recently reported no significant AEs with TCZ monotherapy and improvement rates of 100% for fever, 75.0% for arthralgia, and 71.4% for eruption at 6 months in patients with AOSD [90].Evidence from case reports, small studies, and retrospective studies suggest that TCZ may be an effective therapeutic option in vasculitis syndromes other than GCA, including systemic rheumatoid vasculitis, PMR, Takayasu arteritis, and Behçet's disease [91][92][93][94][95][96]. TCZ has also shown promise in several other indications, including amyloidosis [97-100], FMF [101-103], Schnitzler's syndrome [104,105], and polychondritis [106][107][108][109].…”

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A Review of Recent Advances Using Tocilizumab in the Treatment of Rheumatic Diseases

et al. 2018

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Tocilizumab (TCZ) is the first humanized antiinterleukin-6 (IL-6) receptor monoclonal antibody approved for the treatment of patients with rheumatoid arthritis (RA), Castleman's disease, polyarticular and systemic juvenile idiopathic arthritis, and, most recently, giant cell arteritis as well as for the treatment of chimeric antigen receptor T cell therapy-induced cytokine release syndrome. The global clinical development program for TCZ provides a wealth of clinical data on intravenous TCZ, and more recent studies in patients with RA have provided evidence characterizing the role of intravenous TCZ as monotherapy in early disease and led to the introduction of a subcutaneous formulation of TCZ. In addition, recently published open-label extension and observational studies continue to support the longterm efficacy and safety of TCZ in both clinical trial and real-world settings. Given the involvement of IL-6-mediated signaling in inflammatory disorders, TCZ is also being investigated in other immunological diseases. In particular, a phase 2 trial on the safety and efficacy of subcutaneous TCZ in adults with systemic sclerosis shows clinically relevant improvements in skin sclerosis and lung function in these patients. Another anti-IL-6 receptor agent, sarilumab, targeting the IL6 receptor alpha subunit, was recently approved for the treatment of patients with RA, although longterm data for this biologic are not yet published. In this article we review the placement of TCZ in current treatment guidelines; recent clinical trial data, including quality of life in patients with RA; recent updates to the TCZ safety profile; recent investigations of TCZ in other immunological diseases; and the clinical development of other novel IL-6-targeted agents. Keywords: Interleukin-6; Rheumatoid arthritis; Tocilizumab TOCILIZUMAB: THE FIRST INTERLEUKIN-6 RECEPTOR-NEUTRALIZING BIOLOGICInterleukin-6 (IL-6) is a multifunctional cytokine that plays an important role in both acute and chronic inflammatory responses. Consequently, the dysregulated or persistent production of IL-6 can lead to the development of inflammatory disorders [1]. Elevated levels of IL-6 in serum, synovial fluid, and various tissues have been correlated with disease activity in patients with rheumatoid arthritis (RA) [2], juvenile idiopathic arthritis (JIA) [3,4], Castleman's disease [5,6], systemic sclerosis (SSc) [7], giant cell arteritis (GCA) [8,9], adult-onset Still's disease (AOSD) [10], familial Mediterranean fever (FMF) [11,12], Schnitzler's syndrome [13,14], polychondritis [15], and amyloidosis [1]. These associations suggest a pathogenetic role for IL-6 in multiple inflammatory conditions and form the basis of the rationale for the development of anti-IL-6 therapies.Tocilizumab (TCZ) is the first humanized monoclonal antibody targeting the IL-6 receptor subunit alpha (IL-6Ra) [16], and its mechanism of action has been described in detail in previous reviews [17,18]. Briefly, TCZ targets both membrane-bound and soluble IL-6Ra, which prevents t...

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A Review of Recent Advances Using Tocilizumab in the Treatment of Rheumatic Diseases

et al. 2018

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“…A há-roméves relapsusmentes túlélés 91% volt, ugyanakkor a követési periódusban a betegek 40%-ánál kellett másik készítményre váltani. A TNF-α-gátlókkal, illetve a TCZvel kezeltek hasonló arányban reagáltak a kezelésre, a vascularis szövődmények és a relapsusmentes túlélés tekintetében is [67].…”

Section: A Takayasu-arteritis Kezeléseunclassified

“…Tocilizumabbal az első sikeres kezelésről 2008-ban szá-moltak be [70], ezt követően számos kohorszvizsgálat történt refrakter TA-ban. Ez idáig mintegy 70 eset ismert az irodalomból, ahol 8 mg/kg dózisban négyhe-tente kaptak a betegek tocilizumabot [67,[71][72][73][74][75], több mint 80%-ukban volt hatékony a TCZ, és a kezelés folytatása mellett kevesebb mint 20%-uk relabált. A legnagyobb esettanulmány-sorozat 10, szteroidra és hagyományos DMARD-okra refrakter beteg esetén vizsgálta a szer hatékonyságát és biztonságosságát: a negyedik infú-zió után minden beteg remisszóba került, gyulladásos paramétereik normalizálódtak, azonban a következő há-rom hónap során a betegek harmada angiológiailag is igazoltan relabált [76].…”

Section: A Takayasu-arteritis Kezeléseunclassified

“…A számos kedvező tapasztalat mellett ugyanakkor óva-tosságra int, hogy egy 49 beteg kezelését áttekintő multicentrikus retrospektív tanulmány alapján a betegek 29%-ában legalább egy alkalommal biológiai terápiás szert kellett váltani [79]. Emellett a TCZ nem kuratív, a gyógyszer elhagyása után kettő-négy hónappal gyakoriak a relapsusok.…”

Section: A Takayasu-arteritis Kezeléseunclassified

“…Egyelőre nem állnak rendelkezésre adatok arról, hogy az IL-6-gátló adásának befejezése után fenntartó terápiaként adott konvencionális DMARD-okkal a relapsus kivédhető-e [73,76]. Összes-ségében elmondhatjuk, hogy a TCZ effektívnek tűnik refrakter TA-ban, de a frissen diagnosztizált, konvencionális immunszuppresszívum, illetve TNF-α-gátló naiv betegek körében még kevés adat áll rendelkezésünkre [5, 43,47,67,73]. Egy fázis III-as, nyílt vizsgálat folyamatban van az első vonalbeli szerként adott TCZ haté-konyságának felmérésére TA-betegekben.…”

Section: A Takayasu-arteritis Kezeléseunclassified

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Nagyérvasculitisek korszerű kezelése

Szabó

Kiss

2017

Orvosi Hetilap

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A nagyérvasculitisek közé sorolt óriássejtes arteritisben és Takayasu-arteritisben közös az érfal patogenetikai eltérése, ez alapján felmerül, hogy nem két külön entitásról, hanem egy betegség két megnyilvánulási formájáról van szó. Kezelésükben továbbra is a glükokortikoidé a vezető szerep, szükség esetén cyclophosphamiddal, azatioprinnal, mycofenolat mofetillel kiegészítve. Tekintettel arra, hogy a betegek jelentős része a konvencionális betegségmódosító szerek mellett is szteroiddependens, egyre több klinikai tapasztalat gyűlik a hosszú távú mellékhatások elkerülése ér-dekében adott biológiai terápiás szerek hatékonyságáról. A szerzők célja az új terápiás lehetőségek áttekintése. A tumornekrózis-faktor-alfa-gátlókkal jó terápiás eredmények vannak Takayasu-arteritisben, de óriássejtes arteritisben nem bizonyultak kellően hatékonynak, ugyanakkor az interleukin-6-gátlóval mindkét betegségben szignifikáns javulást sikerült elérni. Az abatacept és az ustekinumab is ígéretesnek tűnik a nagyérvasculitisek kezelésében. Orv. Hetil., 2017, 158(1), 5-12.Kulcsszavak: óriássejtes arteritis, Takayasu-arteritis, tocilizumab, abatacept, ustekinumab Recent advances in the treatment of large vessel vasculitidesGiant cell arteritis and Takayasu arteritis classified to large vessel vasculitides have similar histopathology in the vascular wall proposing that these entities can be different phenotypes on a spectrum of a single disorder. Glucocorticoids are the mainstay of therapy combined with cyclophosphamide, azatioprine and mycofenolate mofetil, when it is required. However, a significant proportion of patients are glucocorticoid-dependent despite of the conventional disease-modifying antirheumatic drugs and suffer from serious side effects of the steroids, therefore alternate options for more effective disease management are needed. The article reviews the advances in the treatment of large vessel vasculitides. Tumor necrosis factor-alpha inhibitors seem to be effective in Takayasu arteritis, but have a little benefit in giant cell arteritis. Interleukin-6 inhibitor appears very promising in both refractory giant cell arteritis and Takayasu arteritis as well. Abatacept and ustekinumab also seem to be a good choice for the therapy. ÖSSZEFOGLALÓ KÖZLEMÉNYRövidítések BAFF = (B-cell activating factor) B-sejt-aktiváló faktor; CTLA-4 = (cytotoxic T-lymphocyte-associated protein 4) citotoxikus Tlymphocyta-asszociált fehérje-4; CYC = cyclophosphamid; DMARD = (disease-modifying antirheumatic drug) betegség-módosító antireumatikus szer; GC = glükokortikoid; GCA = (giant cell arteritis) óriássejtes arteritis; HLA = humán leukocyta-antigén; ICAM-1 = (intercellular cell adhesion molecule-1) intercelluláris sejtadhéziós molekula-1; IFN-γ = interferon-γ; IL = interleukin; ISU = immunszuppresszív; LVV = (large vessel vasculitis) nagyérvasculitis; MTX = methotrexat; PDGF = (platelet-derived growth factor) thrombocytaeredetű növeke-dési faktor; ROCK = (rho kinase) rho-kináz; TA = Takayasuarteritis; TCZ = tocilizumab; TGF-β = (transforming grow...

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2021 American College of Rheumatology/Vasculitis Foundation Guideline for the Management of Giant Cell Arteritis and Takayasu Arteritis

Maz

Chung

Abril

et al. 2021

Arthritis Care & Research

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Objective. To provide evidence-based recommendations and expert guidance for the management of giant cell arteritis (GCA) and Takayasu arteritis (TAK) as exemplars of large vessel vasculitis.Methods. Clinical questions regarding diagnostic testing, treatment, and management were developed in the population, intervention, comparator, and outcome (PICO) format for GCA and TAK (27 for GCA, 27 for TAK). Systematic literature reviews were conducted for each PICO question. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of the evidence. Recommendations were developed by the Voting Panel, comprising adult and pediatric rheumatologists and patients. Each recommendation required ≥70% consensus among the Voting Panel.Results. We present 22 recommendations and 2 ungraded position statements for GCA, and 20 recommendations and 1 ungraded position statement for TAK. These recommendations and statements address clinical questions relating to the use of diagnostic testing, including imaging, treatments, and surgical interventions in GCA and TAK. Recommendations for GCA include support for the use of glucocorticoid-sparing immunosuppressive agents and the use of imaging to identify large vessel involvement. Recommendations for TAK include the use of nonglucocorticoid immunosuppressive agents with glucocorticoids as initial therapy. There were only 2 strong recommendations; the remaining recommendations were conditional due to the low quality of evidence available for most PICO questions.Conclusion. These recommendations provide guidance regarding the evaluation and management of patients with GCA and TAK, including diagnostic strategies, use of pharmacologic agents, and surgical interventions.Guidelines and recommendations developed and/or endorsed by the American College of Rheumatology (ACR) are intended to provide guidance for particular patterns of practice and not to dictate the care of a particular patient. The ACR considers adherence to the recommendations within this guideline to be voluntary, with the ultimate determination regarding their application to be made by the physician in light of each patient's individual circumstances. Guidelines and recommendations are intended to promote beneficial or desirable outcomes but cannot guarantee any specific outcome. Guidelines and recommendations developed and endorsed by the ACR are subject to periodic revision as warranted by the evolution of medical knowledge, technology, and practice. ACR recommendations are not intended to dictate payment or insurance decisions, and drug formularies or other third-party analyses that cite ACR guidelines should state this. These recommendations cannot adequately convey all uncertainties and nuances of patient care.

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Efficacy of tocilizumab in Takayasu arteritis: Multicenter retrospective study of 46 patients

Cited by 69 publications

References 15 publications

A Review of Recent Advances Using Tocilizumab in the Treatment of Rheumatic Diseases

A Review of Recent Advances Using Tocilizumab in the Treatment of Rheumatic Diseases

Nagyérvasculitisek korszerű kezelése

2021 American College of Rheumatology/Vasculitis Foundation Guideline for the Management of Giant Cell Arteritis and Takayasu Arteritis

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