Tocilizumab for induction and maintenance of remission in giant cell arteritis: a phase 2, randomised, double-blind, placebo-controlled trial

Villiger, Peter M.; Adler, Sabine; Kuchen, Stefan; Wermelinger, Felix; Dan, Diana; Fiege, Veronika; Bütikofer, Lukas; Seitz, Michael; Reichenbach, Stephan

doi:10.1016/s0140-6736(16)00560-2

Cited by 497 publications

(386 citation statements)

References 21 publications

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“…У больных ГКА час-тота достижения ремиссии в результате лечения ТЦЗ была достоверно выше, чем в группе плацебо (р=0,03-0,0001), как и безрецидивная выживаемость после 52 нед терапии ТЦЗ (соответственно 85 и 20%; р≤0,001), частота серьез-ных НР составила 14-35% [13][14][15]. Сравнение результатов двух РПКИ позволяет предположить, что внутривенное введение ТЦЗ может быть более эффективным, чем под-кожные инъекции [13][14][15]. Интересно, что при назначе-нии ТЦЗ больным артериитом Такаясу в одном сообщении отмечено развитие рецидива после перевода на подкожное введение [25].…”

Section: Discussionunclassified

“…Опубликованные в 2016 г. ре-зультаты двух двойных слепых рандомизированных плаце-боконтролируемых исследований (РПКИ) ТЦЗ у больных ГКА продемонстрировали его эффективность и приемле-мую безопасность для индукционной и поддерживающей терапии [13][14][15], подтвердив полученные ранее выводы небольших предварительных клинических исследований ТЦЗ при ГКА тяжелого течения, которые публикуют начи-ная с 2011 г. [16,17].…”

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Experience With Tocilizumab, an Interleukin 6 Inhibitor, Used for the Treatment of Giant Cell Arteritis With Severe Comorbidity

Бекетова¹,

Ushakova²,

Никишина³

et al. 2018

rsp

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Section: Discussionunclassified

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Experience With Tocilizumab, an Interleukin 6 Inhibitor, Used for the Treatment of Giant Cell Arteritis With Severe Comorbidity

Бекетова¹,

Ushakova²,

Никишина³

et al. 2018

rsp

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“…Egy év múlva mind a teljes remisszió elérésében (85 vs. 40%), mind a relapsusmentes túlélésben (85 vs. 20%) szignifikánsan jobbnak bizonyult a TCZ a placebó-nál. Súlyos nem kívánt esemény a hatóanyagot kapók 35%-ánál, a placebokar 50%-ánál lépett fel [50]. További adatok várhatóak a szer hatékonyságával és biztonságos-ságával kapcsolatban egy 119 újonnan diagnosztizált és 122 relabáló beteg bevonásával jelenleg is folyó fázis IIIas, multicentrikus, randomizált kettős vak, placebokontrollált vizsgálatból (GiACTA) [51].…”

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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“…Glucocorticoid sparing treatment strategies at best demonstrated moderate effi cacy (methotrexate) or even failed to show a clinically signifi cant eff ect (TNFα inhibitors) [1]. According to several case series, the humanized monoclonal antibody against the Interleukin-6 receptor, tocilizumab (TCZ), could be eff ective in relieving symptoms and reducing the cumulative glucocorticoid dose in patients suff ering from GCA [1].Recently, the fi rst phase 2, randomized, double-blind, placebo-controlled trial assessing tocilizumab for induction and maintenance of remission in giant cell arteritis was published [2].This investigator initiated, single center study randomized (2:1) 30 patients with newly diagnosed or relapsing GCA fulfi lling the 1990 ACR-criteria to receive TCZ (8 mg/kg intravenously) or placebo every 4 weeks until week 52 [2]. All patients were treated with oral prednisolone, initially at a dose of 1 mg/kg/day and then rapidly tapered to 0.1 mg/kg/day at week 12.…”

mentioning

confidence: 99%

“…Recently, the fi rst phase 2, randomized, double-blind, placebo-controlled trial assessing tocilizumab for induction and maintenance of remission in giant cell arteritis was published [2].…”

mentioning

confidence: 99%

Targeting Interleukin-6 in the treatment of giant cell arteritis: hope or hype?

Czihal

2016

Vasa

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Glucocorticoids still are the cornerstone in the medical treatment of giant cell arteritis (GCA), the most common form of the primary systemic vasculitides. However, recurrences are common during glucocorticoid tapering and most of the patients experience treatment-related adverse events. Glucocorticoid sparing treatment strategies at best demonstrated moderate effi cacy (methotrexate) or even failed to show a clinically signifi cant eff ect (TNFα inhibitors) [1]. According to several case series, the humanized monoclonal antibody against the Interleukin-6 receptor, tocilizumab (TCZ), could be eff ective in relieving symptoms and reducing the cumulative glucocorticoid dose in patients suff ering from GCA [1].Recently, the fi rst phase 2, randomized, double-blind, placebo-controlled trial assessing tocilizumab for induction and maintenance of remission in giant cell arteritis was published [2].This investigator initiated, single center study randomized (2:1) 30 patients with newly diagnosed or relapsing GCA fulfi lling the 1990 ACR-criteria to receive TCZ (8 mg/kg intravenously) or placebo every 4 weeks until week 52 [2]. All patients were treated with oral prednisolone, initially at a dose of 1 mg/kg/day and then rapidly tapered to 0.1 mg/kg/day at week 12. The majority (23/30) of patients had new-onset disease. The primary outcome was defi ned as the proportion of patients who achieved complete remission of disease at week 12 and was reached by 17 (85 %) of 20 patients in the TCZ-group and four (40%) of ten patients in the placebo-group (p = 0.03). Secondary effi cacy endpoints such as the relapse-free survival at week 52 (85 % vs. 20 %; p = 0.001) and the cumulative prednisolone dose at week 52 (43 mg/kg vs. 110 mg/kg; p = 0.0005) were also in favour of TCZ-treatment. At the end of the trial, prednisolone treatment could be terminated in 80% of TCZ-treated patients but only 20% of patients in the placebo-group ( p = 0.004). The overall rate of adverse events did not diff er between groups. However, infectious complications were more common in the TCZarm compared to the placebo-arm (10 episodes vs. 1 episode), and 9 episodes of neutropenia occurred in 4 patients treated with TCZ.Although the sample size is small, this well conducted study provides compelling evidence on the clinical efficacy of interleukin-6-inhibition in inducing and maintaining clinical remission in GCA. Of note, glucocorticoid tapering was performed much more rapidly than in usual clinical practice in order to reveal even small clinical eff ects of TCZ-treatment. This explains the high rate of recurrences in the placebo-group. The considerable number of infectious complications under TCZ-treatment must be considered when translating the study`s results to clinical practice.TCZ can now be regarded as the most eff ective glucocorticoid sparing agent in the treatment of GCA. Case reports also documented the feasibility of a glucocorticoidfree treatment regimen with TCZ-monotherapy [3]. However, ongoing arterial infl ammation despite clinical an...

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Tocilizumab for induction and maintenance of remission in giant cell arteritis: a phase 2, randomised, double-blind, placebo-controlled trial

Cited by 497 publications

References 21 publications

Experience With Tocilizumab, an Interleukin 6 Inhibitor, Used for the Treatment of Giant Cell Arteritis With Severe Comorbidity

Experience With Tocilizumab, an Interleukin 6 Inhibitor, Used for the Treatment of Giant Cell Arteritis With Severe Comorbidity

Nagyérvasculitisek korszerű kezelése

Targeting Interleukin-6 in the treatment of giant cell arteritis: hope or hype?

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