Tocilizumab: a novel therapy for patients with large-vessel vasculitis

Salvarani, Carlo; Magnani, Luca; Catanoso, Mariagrazia; Pipitone, Nicolò; Versari, Annibale; Dardani, Lucia; Pulsatelli, Lia; Melicòni, Riccardo; Boiardi, Luigi

doi:10.1093/rheumatology/ker296

Cited by 212 publications

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“…[20][21][22] We observed a "reverse remodeling" effect of TCZ on the thickened arterial walls in 2 patients in our study through continuous long-term administration of TCZ (Table II, Figure 1 and Figure 2), while we observed no worsening of the thickened arterial lesions in the other 2 patients. Furthermore, GC was tapered off in two patients (cases 3 and 4) and the dosage of GC was gradually decreased to 2 mg/day (case 1) and 3 mg/day (case 2) during this study period (Table II).…”

Section: Discussionsupporting

confidence: 46%

“…In 2011, Salvarani, et al reported a pilot study of 4 patients with LVV (2 with GCA and 2 with TA) treated with TCZ (8 mg/kg/month) for 6 months followed by MTX maintenance therapy. 20) Two patients were treatment-naïve and the other two patients had relapsing disease. Three patients entered complete clinical remission and 1 case achieved partial response.…”

Section: Discussionmentioning

confidence: 99%

“…In two relapsing patients who had been treated with GC at initial infusion of TCZ, prednisolone was tapered off or gradually decreased to 2.5 mg/day by the end of the TCZ treatment. 20) Urizony, et al treated 10 patients with GCA (n = 7), TA (n = 2), and PMR (n = 1) with TCZ for a mean period of 7.8 months (range, 4-12 months). 22) All patients entered and maintained clinical remission during TCZ therapy.…”

Section: Discussionmentioning

confidence: 99%

“…Several recent studies have reported that IL-6 receptor (IL-6R) blockade with the IL-6R monoclonal antibody tocilizumab (TCZ) might be effective for the treatment of patients with refractory TA. [19][20][21][22] Since the mean time of TCZ administration in 3 recent pilot studies is a bit short (range, 3 to 12), [20][21][22] the safety and effi cacy of TCZ for patients with refractory TA need to be examined for longer periods. Here, we assessed the clinical, serological, and crosssectional imaging outcomes of 4 patients with refractory TA who were administered TCZ more than 24 times.…”

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Tocilizumab for the Treatment of Patients With Refractory Takayasu Arteritis

et al. 2013

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SummaryTreatment of refractory Takayasu arteritis (TA) remains an unresolved clinical issue. Patients usually respond to glucocorticoid (GC) therapy, but often relapse on tapering of the GC dose. The aim of the present study was to assess the safety and effi cacy of the interleukin-6 (IL-6) receptor antibody tocilizumab (TCZ) in patients with TA refractory to conventional therapies including GC. Four patients with TA who had shown GC resistance received TCZ infusions (8 mg/ kg) every 4 weeks a total of at least 24 times (range, 24 to 51). Clinical symptoms, the serum levels of acute phase proteins and IL-6, GC dosage necessary to maintain remission, and cross-sectional imaging by enhanced CT and MRI were assessed. All patients achieved good clinical response and rapid normalization of the acute phase proteins such as C-reactive protein and serum amyloid A during the therapy with TCZ. The mean dosage of prednisolone could be reduced from 21.3 mg/day to 1.5 mg/day. Although the serum IL-6 level was transiently elevated in all patients after several TCZ infusions, it gradually recovered to the initial level. Along with the decrease of serum IL-6, two patients exhibited significant reduction in thickened arterial lesions. No drug-related adverse effects were noted. In this small group of patients with refractory TA, TCZ therapy was effective and well-tolerated. Further larger studies should be conducted to confi rm this fi nding. (Int Heart J 2013; 54: 405-411)

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Section: Discussionsupporting

confidence: 46%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Tocilizumab for the Treatment of Patients With Refractory Takayasu Arteritis

et al. 2013

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“…Számos kisebb tanulmány és esetriport is hatékonynak találta GCA kezelésében [39][40][41][42][43][44][45][46][47][48].…”

Section: öSszefoglaló Közleményunclassified

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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