Clinical use of subcutaneous Abatacept in the treatment of rheumatoid arthritis Текст научной статьи по специальности «Фундаментальная медицина»

of RHEUMATOLOGY

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ANAXKOnHXH REViEW

H kAivikh xpnoipoinTa tou unoSopiwq xopnYoupevou Abatacept oin Bepaneia inq PeupaioeiSouq ApBpiiiSaq.

BaoiAiKr]-KaAAi6nr| Mnoupvia, neipoq n. I0r|KaKr|q

A' nponaiSeuTiKH naBoAoYiKH KAivikh, IcnpiKfi IxoAfi, EBviKo Kai KanoSioipiaKo navenioTHMio ABnvwv

nEPIAHYH

To abatacept, evaq |3ioAoYiK6q napaYoviaq Yia in Bepaneia inq peupaioeiSouq apBpiiiSaq nou Spa peow avaoioAHq inq ouvSieYeponq iwv T-Aep0oKuTTapwv, anoieAei to npwio oKeuaopa auiqq inq KainYopiaq nou eYive SiaBeoipo tooo oe evSo0Ae|3ia ooo Kai oe unoSopia pop0n xopHYnonq. ^inv napouoa epYaoia avaoKonouviai ia eupHpaia iwv peAeiwv nou Siepeuvouv inv ao0aAeia Kai inv anoieAeopaTiKOTnTa iou unoSopiou abatacept. napoii Sev unapxouv aKopn noAAa SeSopeva Yia in paKpoxpovia eKBeon iwv aoBevwv oio unoSopio abatacept, to oKeuaopa

0aiveiai va eivai e^ioou ao0aAeq Kai anoieAeopaiiKo pe to evSo0Ae|iwq xopnYoupevo. Oi peAeieq Seixvouv oii n avoooYoviKoinia iou unoSopiou abatacept eivai piKpH Kai ia xapaKinpioiiKa ao0aAeiaq Kai anoTeAeopaTiKoTniaq iou ouYKpioipa pe eKeiva iou unoSopiou adalimumab. Me SeSopevn in onpaoia inq oSou xopHYnonq oinv eniAoYH iou KaiaAAnAoiepou Yia iov KaBe aoBevH |ioAoyikou napaYovia, n SiaBeoipoTnia iou abatacept tooo oinv evSo0Ae|ia ooo Kai oinv unoSopia pop0n anoieAei pia eunpooSeKin npooB^n oin BepaneuiiKH 0apeipa iou peupaioAoYou.

Ynsu8uvoq AAAr|Aoypa0iaq;

Ka8nvnTnQ nexpoQ n.

MovaSa PeupaToAoyiaQ A' nponaiSeuTiKiiq

na8oAoyiKHQ KAIVIKHQ,

AaiKO NoaoKopeio, laTpiKi 2xoAi

E8viKO Kai KanoSiCTrpiaKO naveniCTiiMio A8qvuv

TnA:213-2061061, 213-2061307

210-7791839 E-mail: psfikakis@med.uoa.gr Corresponding author; Professor Petros P. Sfikakis

Rheumatology Unit, 1st Departemnt of Propedeytic

Internal Medicine

Laiko Hospital, Medical School

National kapodistrian University of Athens, Athens

Tel: 213-2061061, 213-2061307

Fax: 210-7791839

E-mail: psfikakis@med.uoa.gr

Mediterr J Rheumatol 2015; 26(2): 44-53

Ae^eiq-KAeiSia: PeupaioeiSnq apBp'mSa, unoSopio abatacept

of RHEUMATOLOGY

eaahnikh peymatqaoria

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2015

Clinical use of subcutaneous Abatacept in the treatment of rheumatoid arthritis.

Vasiliki-Kalliopi Bournia, Petros Sfikakis

Rheumatology Unit, First Department of Propedeutic and Internal Medicine, Athens University Medical School.

ABSTRACT

Abatacept, a biologic disease modifying anti-rheumatic drug approved for the treatment of rheumatoid arthritis acting through inhibition of T-cell co-stimulation, is the first drug of this group to be available for both intravenous and subcutaneous administration. In the present work, we critically review the results of the available studies on the safety and efficacy of subcutaneous abatacept. Although there is no sufficient evidence yet regarding long-term exposure to subcutaneous abatacept, studies show that the subcutaneous form of administration is as equally safe and effective as the intravenous form of abatacept. Immunogenicity does not seem to be an important issue, while a head-to-head trial comparing subcutaneous abatacept to subcutaneous adalimumab supports a similar safety and effectiveness profile of the two biologics. Given the importance of the administration route for choosing the most appropriate biologic drug in each case, the addition of a subcutaneous form of abatacept to the already available intravenous drug is very welcomed by rheumatologists that can now be more flexible in defining their patients' treatment.

Mediterr J Rheumatol 2015; 26(2): 44-53

Keywords: Rheumatoid arthritis, subcutaneous abatacept

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e л л h n i к h реуматолопа 2015

ЕПАГПГН

Тa тeЛeuтaía xpóvía éxouv au^eí oпpavтlкá о1 9e-paпeuтlкéQ eпlЛoYéQ Yía тп peupaтoelбП apBpnrôa, pe тпv epфávloп véwv ßюЛoYlкшv пapaYÓvтwv. H прш^п Kaí eпl9eтlкП 9epaпeía pe oтóxo тпv впи-в^п úфeoпQ п XapпЛПç evepYóтптaQ vóoou aпoтeЛeí пЛе-ov пaYlшpévп пpaктlкП, Ka9wç о1 ao6eveíQ pe 6uopb-veíQ пpoYvwoтlкoúç пapáYovтeQ Kaí vóoo av6eKHKn oтпv aY^Yn прштпс YPappnç avтlpeтwпíZovтаl кaтá Kavóva pe ouvбuaopó тропопо^тиш' i^ç vóoou фappáкwv (DMARDs) п pe тп XPПoп ßюЛoYlкшv пa-paYÓvтwv.1 Oí ßюЛoYlкoí пapáYOvтeQ пои éxouv péxpí onpepa eYKpí6eí Yía тп 9epaпeía i^ç peupaTOe^ùç ap9píтlбaQ бpouv eíтe avaoтéЛЛovтaç pía фЛeYpovw-бп кuттapoкívп, óпwç о пapáYWv véкpwoпç ÓYKwv-a (TNF-a), п lvтepЛeuкívп-1 (IL-1)Kaí п lvтepЛeuкívп-6 (IL-6), eíтe e^aЛeíфovтaç тa B-Лepфoкúттapa, eíтe пape-pпoбíZovтaç то pnvupa ouvбléYepoпç пои aпalтeíтal Yía ir|v пЛпрп evepYOпoíпoп тwv Т-Лepфoкuттápwv.2 То abatacept eívaí pía прштёуп oúviri^ тои Kuira-рото^ю^ Т-Лepфoкuттaplкoú avтlYÓvou 4 (CTLA-4) pe то тpoпoпolПpévo Fc тpПpa тпç av9pwпlvпç avo-oooфalpívпç IgG1. 'Exeí тпv ^ютпто va пpooбéveтal eкЛeкгlкá oтa pópía CD80 Kaí CD86 тпç eпlфávelaç тwv avтlYovoпapouolaoтlкшv Kuirápwv пapepпoбíZo-vтaç éтol тп oúvбeoП тouç otov uпoбoxéa CD28 тwv

Т-Лepфoкuттápwv. Аитп п oúvбeoп кaтaoтéЛЛel тп

peтáбooп evôç пoЛú oпpavтlкoú бeúтepou pпvúpaтoç пои aпalтeíтal Yía тп бléYepoп тwv Т-Лepфoкuттápwv.2 То abatacept, пои péxpí пpóтlvoç Птаv бla9éolpo am^íonrá Yía evбoфЛéßra xopПYПoп, aпoтeЛeí tov пршто ßloЛoYlкó пapáYovтa пои кuкЛoфópпoe iaí wç ипоб0рю oieúaopa. H бleúpuvoп тwv eпlЛoYШv oтп BepaTOía тпç peupaтoelбoúç ap9píтlбaç, pe то peYá-Ло пЛП9oç тим бra9éOlpwv ßk^YHuv пapaYÓvтwv, тп бuvaтóтптa xpПoпÇ Kaí áЛЛwv пapaYÓvтwv пЛпv тwv anti-TNF-a wç aYWYnç прштк YPappnç, aЛЛá Kaí nç бlaфopeтlKéç oбoúç xopПYПOПÇ тим фappáкwv, пapéxel peYaЛúтepп eueЛl^ía oтo 9epáпovтa, avará-фeuкш ôpwç бпploupYeí Kaí пoЛЛá epumipanrá. Zir|v пapoúoa avaoкóппoп Yíveтal пpooпá9ela va ouvoфl-o9oúv тa eupПpaтa тим peЛeтwv пои бlepeuvoúv ir|v aoфáЛela Kaí тпv aпoтeЛeopaтlкóтптa тои uпoбopíwç XopпYoupévou abatacept Kaí va a^;юЛoYп9eí п oпpaoía тпç бuvaтóтптaç xopПYПOПÇ тои oкeuáopaтoç тóoo oe evбoфЛéßla óoo Kaí oe ипоб0рга popфП.

МЕООЛОЕ

AvaZптПoape oтo PubMed пpóoфaтeç бпpooleú-oelç oe ßá9oç 10eтíaç, xPП0lpoпolwvтаç тouç ópouç "abatacept" Kaí "subcutaneous". Пpoéкuфаv 49 aro-тeЛéopaтa, eK тwv oпoíwv тa 10 aфopoúoav oe kM-vlKéç peЛéтeç Kaí onç eTOKraoe^ touç (oe a^éç ou-YкaтaЛéYovтal pía peЛéтп фáoпç II/III, pía фáoпç III Kaí пévтe peЛéтeç фáoпç IIIb).

АПОТЕЛЕЕМАТА

а. Лебореуа АпотеЛеамат1к0тптад

То пршто epú^pa пои avaKúm"eí avaфoplкá pe тпv aпoтeЛeopaтlкóтптa тои uпoбopíшç xopПYoúpevou abatacept oxenZeTOí pe то кaтá пóoov п ßюбra9eol-póтптa тои oкeuáopaтoç e^peáCeraí aró тпv об0 XopПYПOПÇ. Mía 61пЛП тифЛп, тuxaюп0lпpévп, eЛeY-xópevп pe e^vírá фáppaкo peЛéтп фáoпç IIa, eÇé-тaoe бláфopa бoooЛoYlкá oxПpaтa sc abatacept oe 68 ao9eve^ pe peupaтoelбП ap9píтlбa Kaí кaтéЛп^e oтo ouprápaopa ón п X0pПYП0П 125mg abatacept uпoбopíwç avá eßбopáбa, ave^ap^wç oupanraú ßápouç тои ao9evoúç, eпlтuYXável eпíпeбa фappá-Küu oto nAáopa пapópola pe eKeíva пои eпeтeúx9п-oav oe 149 ao9eve^ pe peupaтoelбП ap9píтlбa пои éЛaßav то eYкeкplpévo evбoфЛéßю бoooЛoYlкó oxnpa тwv 10mg/Kg.3

Oí é^í кuplóтepeç тuxaюпolПPéveç peЛéтeç, фáoпç III, пои eпéтpeфav тпv a^;юЛóYП0П тпç aпoтeЛeopaтlкó-тптaç тпç uпoбóplaç popфПç тои abatacept nrav п ACQUIRE (Abatacept Comparison of Subcutaneous versus Intravenous in Inadequate Responders to Methotrexate),4 п ACCOMPANY (Abatacept in Subjects with Rheumatoid Arthritis Administered Plus or Minus Background Methotrexate Subcutaneously),5 п ALLOW (Evaluation of Abatacept Administered Subcutaneously in Adults with Active Rheumatoid Arthritis: Impact of Withdrawal and Reintroduction on Immunogenicity, Efficacy and Safety),6 п ATTUNE (Abatacept in Subjects who Switch from Intravenous to Subcutaneous Therapy),7 п AMPLE (Abatacept versus Adalimumab Comparison in Biologic-Naïve Rheumatoid Arthritis Subjects with Background Methotrexate)8 Kaí П AVERT (Assessing Very Early Rheumatoid Arthritis Treatment). 9 Та oпpavтlкóтepa eupnpara тwv peЛe-iúv au^v ouvoфíZovтal oтov nívaKa 1. H прштп aпó nç пpoavaфep9eíoeç peЛéтeç, п ACQUIRE4, ouvéKpíve тпv aoфáЛela Kaí aпoтeЛe-opaтlкóтптa тои ипоборюи évavn тои evбoфЛeßíou abatacept oe ao9eve^ pe evepYó peupaтoelбП ap9pí-тlбa пои eíxav aпoтúxel oe 9epaTOía pe pe9oтpe^áтп. Ze au^ тп бlпЛá тифЛп peЛéтп aпóбel^пç PП гатш-тepóтптaç, бlápкelaç 6 pпvшv, 693 ao9eveíç iuxaí-oпolП9пкav va Лáßouv pía apxíKn evбoфЛéßla бóoп фópтloпç 10mg/Kg, aкoЛou9oúpevп ará 125mg abatacept uпoбopíшç avá eßбopáбa, evú 676 ao9e-veíç тuxaloпolП9пкav oтпv opáбa тou evбoфЛeßíou abatacept, oir| ouvП9п бóoп тwv 10mg/kg катá nç Пpépeç 1, 15, 29 Kaí aкoЛoú9wç avá 4 eßбopáбeç. То apxíKó кaтaЛпкгlкó oпpeío тпç peЛéтпç Птav п avra-пóкploп oúpфwva pe то бeíкгп ACR20 oтouç 6 pnveç. H aпávтпoп oтп 9epaпeía Птav ouy^o^ onç бúo opáбeç, тóoo Yía то бeíкгп ACR20 (76% vs 75.8%), óoo Kaí Yía touç ACR50 Kaí ACR70 (50.2%

vs 48.6% Kaí 25.8% vs 24.2% Yía тпv opáбa тou uпo-

H KAINIKH XPHIIMOTHTATOY YnOAOPIQI XOPHEOYMENOY ABATACEPT ITH QEPAnEIATHI PEYMATOEIAOYI AP0PITAAI CUNiCAL USE OF SUBCUTANEOUS ABATACEPT iN THE TREATMENT OF RHEUMATOiD ARTHRiTiS

nivaKaç 1. tou oxeôiaoMoû Kai twv ßaoiKwv eupnMâTwv twv meAetwv фаопс lllb nou açioÀoYoûv то

unoôôpio Abatacept.

мелетп ACQUIRE (4) ACCOMPANY(5) ALLOW (6) ATTUNE (7) AMPLE (8) AVERT (9)

Ixs6iaojôç SinAa ru$Ar|, anOSsi^nQ Mn KaTWTspoTnTaQ avoixroi oxs6iaojoi, |jr| sЛsYXÖJSVn, jn ruxaionoinjsvn ôinÀâ TU$Àn, £À£YXÔMsvn |j£ placebo, Tuxaionoinjsvn avoixroi oxsöiaojiou, jn sЛsYXÔJsvn, jn ruxaionoinjsvn апЛâ тифЛг|, ruxaionoinjsvn JsЛsтn oÙYKpionç 2 ßюЛoYlкшv napaYÔvrov бтЛа ^фЛ!, ruxaionoinjsvn

AiâpKsia 6 MivsQ 4 jnvsç 9 jnvsç 12 jnvsç 24 jnvsç 24 jnvsç

ПЛг|Эиорс^ ао9еушу 1457 aa8svsic; Ms svspyo PA (Mn avranoKpian dn MTX) 100 ao9svsiç js svspYÖ PAKai anoruxia os 1 TC^axioro DMARD 167 aoGsvsiç js svspYÔ PA (jn avranoKpion oTn MTX) 123 ao9svsiç js svspYÖ PA (jn avranÔKpion os MTX n anti-TNFa) 646 ao9svsiç js svspYÖ PA xwP'ç nponYoijsvn л|фп PloЛoYlкшv (jn avranÔKpion orn MTX) 351 ao9svsiç js npwijn svspYÔ PA (nponYoijsvn лпфп MTX<4wks)

Аушуп sc ABA + MTX vs iv ABA + MTX sc ABA+ MTX vs sc ABA sc ABA (phase I)à sc ABA vs Placebo (Phase II)à sc ABA (Phase III) sc ABA sc ABA + MTX vs sc ADA+MTX sc ABA + MTX vs sc ABA vs MTX

noooorô DAS28<2.6

Прштарх1ко КатаЛпкт1ко Injsio nOOOOTO avranoKpianQ Kara ACR20 otouq 6 MivsQ Avoooyoviko-rnra orouç 4 jnvsç AvoooYoviKÔTn-Ta Kai ao^âÀsia otouç 6 jnvsç AoфclЛsla orouç 3 jnvsç jsra rnv c^aYn anô iv Abatacept noooorô avranÔKpionç Kara ACR20 oro sroç orouç 12 jnvsç Kai noooorô DAS28<2.6 orouç 12 Kai 18 jnvsç Yia to sc ABA + MTXvsMTX

noooorô avranÔKpionç ACR20 otouq 6 MivsQ: 76% (sc ABA) vs. 75.8% (iv ABA) DAS28<2.6 orouç 4 jnvsç: 32.6% (sc ABA) vs. 29.8% (sc ABA+MTX) DAS28<2.6 otouç 9 jnvsç: 69.8% (sc ABA-phaselI) vs. 63.5% (placebo phase II) DAS28<2.6 oro sroç: 39.8% ACR20 oro sroç: 64.8% (sc ABA) vs 63.4% (sc ADA) DAS28<2.6 oro sroç: 60.9% (sc ABA+MTX) vs 45.2% (MTX) vs 42.5% (scABA)

lopapsç Avsm9ùjnrsç Evépysisç 4.2% sc ABA) vs. 4.9% (iv ABA) 3.9% sc ABA+ MTX vs. 6.1% sc ABA 1,8% phase I, 2.5% phase II, 2.3% phase III 10.6% 10,1% (sc ABA) vs 9.1% (sc ADA) 6.7% (sc aba+mtx) vs 7.8% (MTX vs 12.1% (sc ABA)

ABA: abatacept, MTX: je6oTpeE;âTn, ADA: adalimumab, sc: subcutaneous, iv: intravenous.

ôopiou Kai Tou ev6oфЛeßíou abatacept, avTioToixwç). Omoîwq Kai ме тг| ХРПОП тои ôeÎKTn Disease Activity Score 28-CRP (DAS28-CRP), ôianioTw9nKe napôMoio nooooTô enÎTeu^HQ ифеопс (DAS28-CRP<2,6) Kai xa-Mn^ÎQ evepYÔTHTaQ vôoou (DAS28-CRP<3,2) otouq 6 MnvEQ METa^û twv ôûo oMâôwv (24,2% vs 24,8% i^eon Kai 39,5% vs 41,3% xaMH^Î evepYôTnTa vôoou Yia Tnv oMâôa тои unoSopiou Kai тои evôoфÀeßюu abatacept, avTioToixwQ). EninAéov, Ta ôeôoMéva anô Tnv avoiXTn ф^п enéKTaonQ тпс меАетпс ACQUIRE10 KaTâ Tnv onoia ôÀoi oi ao9eveiç eAaßav unoôôpio abatacept, KaTaôeiKvûouv ôti Ta nooooTâ avTanôKpi-onQ oTnv aY^Yn nou napaTnpn9nKav otouq 6 Mnveç

9epaneiaç ôiaTnpn9nKav Méxpi Kai touq 32 MnveQ Kai napéMeivav ouYKpioiMa MeTa^û twv ôûo apxiKwv 9e-paneuTiKwv oMâôwv.

AvâÀoYa anoTeAéoMaTa éôeiÇe Kai Mia lanwviKn ме-Летп11 ме avTÎoToixo TnQ ACQUIRE oxeôiaoMô, nou npaYMaTonoin9nKe oe ôeÎYMa 118 evnAÎKwv ianwviKnQ KaTaYWYnQ Me evepYô peuMaToeiôn ap9pÎTiôa (> 12 enwôuveQ ap9pwoeiQ, > 10 Sioykwmeveq ap9pwoeiQ Kai CRP > 0.8 mg/dL). Ztiq 169 nMépeQ, n oMâôa nou eAaße unoôôpio abatacept Kai Me9oTpeÇâTn eixe ou-YKpioiMn anôKpion KaTâ ACR20, ACR50 Kai ACR70 Me Tnv oMâôa nou eAaße to ouvôuaoMô evôoфЛeßíou abatacept Me Me9oTpeÇâTn. Omoîwq, ouYKpioiMn MeTa-

of RHEUMATOLOGY 2

e л л h n i к h реуматолог1а 2015

ft тwv 6úo opáбwv Птav п peíwoп тou HAQ-DI, Ka-9ùç Kaí тa пooooтá тwv ao9evúv пou ráTOxav úфe-oп pe ßáoп то бeíкгп DAS28-CRP. Oí 112 ao9eve^ пou пpoxШpпoav oтпv avolxтoú oxeбlaopoú фáoп eпéкгaoпç auтПç тпç peЛéтпç, кaтá i^v oпoía 0Ло1 oí ouppeтéxovтeç éЛaßav uпoбóplo abatacept, бraтПpп-oav i^v úфeoп onç 52 eßбopáбeç, aveftpтПтwç тпç apxlкПç тouç тa^lvópпoпç.12 H peЛéтп ACCOMPANY,5 pía пoЛuкevтplкП, avoíx^ peЛéтп фáoпç IIIb oxeбláo9пкe Yía va aпavтПoel oтo epú^pa av п avoooYovlкóтптa, п aoфáЛela Kaí п aпoтeЛeopaтlкóтптa тou uпoбopíou abatacept впп-peáCeraí aпó тп xopПYПoП тou wç povo9epaпeíaç п oe ouvбuaopó pe pe9oтpeÇáтп. Ап0 touç 100 ao9e-veíç пou evтáx9пкav oтп peЛéтп, 96 oЛoкЛПpwoav i^v apxlкП фáoп бlápкelaç 4 pпvúv Kaí 90 пpoxú-pПoav 0тп фáoп eró^a^. Ап0 auтoúç oí 75 eÇa-кoЛou9oúoav va пapaкoЛou9oúvтal oтa 6úo xpóvía. ПevПvтa évaç ao9eve^ éЛaßav ouvбuaopó uto6opí-ou abatacept pe pe9oтpeÇáтп, evú oí uпóЛolпol 49 éЛaßav uпoбóplo abatacept wç povo9epaTOÍa, xwpíç va пpoпYП9eí evбoфЛéßla бóoп фópтloпç oe Kavéva aпó тa 6úo жёЛп ir|ç peЛéтпç. ztouç 4 pПveç пa-paтпpП9пкe 0UYкpÍ0lpп peíwoп тou DAS28,тпç тáftç тou -1.67 (95% ópía aftorao^ [95% CI] -2.06, -1.28) o^v opáбa тou ouvбuaopoú Kaí -1.94 [95% CI -2.46, -1.42] o^v opáбa тпç povo9epaпeíaç, avnoTOíxa. ПapáЛЛпЛa, бraпloтú9пкe ßeЛтíwoп Kaí ^ç Лelтoup-YlкПç кaтáoтaoпç тwv ao9evúv pe peíwoп тou Health Assessment Questionnaire Disability Index (HAQ-DI) катá -0.3 (95% CI -0.4, -0.2) o^v opáбa тou ouv6u-aopoú Kaí кaтá -0.6 (95% CI -0.7,-0.4) o^v opáбa тпç povo9epaпeíaç. Oí pelûoelç oтпv evepYóтптa ir|ç vóoou пou eпeтeúx9пoav кaтá tov 4o pПva, бют^-9пкav сп"п фáoп eпéкгaoпç тпç peЛéтпç péxpí Kaí тov 18o pПva Yía тouç ao9eveíç пou ouvéxíoav тп Лпфп sc abatacept, ave^ap^wç i^ç тauтóxpovпç ЛПФпç п pп pe9oтpeftтпç кaтá тпv apxlкП фáoп i^ç peЛé-тпç. Kaтá тп фáoп eпéкгaoпç тпç peЛéтпç5 u^pft aváYrai пpoo9Пкпç pe9oтpeftтпç oтo 23,3% тwv TOplrn^ewv пou apxíKá eЛápßavav povo9epaTOÍa. Ztouç 18 pПveç п Pé0П peтaßoЛП тou DAS28 oe oxé-oп pe тпv apxlкП tou тlpП Птav -1.84 (95% CI -2.23, -1.34) Yía тпv opáбa тou ouvбuaopoú pe pe9oтpeÇáтп Kaí -2.86 (95% CI -3.46, -2.27) Yía тпv opáбa тпç po-vo9epaпeíaç pe uпoбóplo abatacept. H peЛéтп ALLOW6 eíxe wç otoxo va eftтáoel тпv avo-ooYovlкóтптa, тпv aoфáЛela Kaí тпv aпoтeЛeopaтl-кóтптa тou ouvбuaopoú тou uto6opíou abatacept pe pe9oтpeftтп oe ao9eve^ pe peupaтoelбП ap9píтlбa oтouç orafouç п X0pПYП0П тou uпoбopíou abatacept бгашпп^ пpoowplvá. H peЛéтп ouprap^aße 167 ao9eveíç pe peupaтoelбП ap9píтlбa, oí oпoíol, aфoú пПpav pía evбoфЛéßla б00П фópтloпç (10mg/Kg), aKo-Лou9oúpevп aпó uпoбóplo abatacept 125mg/eßбo-

páба Yía 12 eßбopáбeç, тuxaloпolП9пкav oe avc^o-Yía 2:1 pe бlпЛá тuфЛó oxeбlaopó, eíтe va ouvexíoouv то uпoбóplo abatacept, efre va Лáßouv placebo Yía áЛЛeç 12 eßбopáбeç. Ii^v тpíтп фáoп тпç peЛéтпç oí ao9eveíç tou eЛápßavav placebo ftK^oav £avá то uto6ópio abatacept Yía nç eràpeveç 12 eßбopáбeç, aфoú пpúта oí píooí topítou aпó auтoúç ^aíoraí-П9пкav va Лáßouv evбoфЛéßla б00п фópтloпç Kaí oí áЛЛol píooí placebo. Ztouç аo9eveíç пou бléкoфav то uпoбóplo abatacept паpатпpП9пкe pí^ eпlбeívwoп тou DAS28 кaтá тп фáoп aпóoupoпç, пou ßeЛтlú-9п!в ôpwç pe тпv eпaveloaYWYП tou фappáкou, éTOí Ш0тв 0то тéЛoç тпç тpíтпç фáoпç тпç peЛéтпç va pпv uпápxel бlaфopá peraft тwv 6úo opáбwv 0то п000-0т0 тwv ao9evúv пou ráTOxav xapпЛП evepYóтптa vóoou (79.7% [95% CI 70.6%, 88.9%] Yía тпv opáбa пou бléкoфe vs 69.2% [95% CI 54.7, 83.7%] Yía тпv opáбa пou ouvéxíoe то abatacept) п úфeoп (63.5% [95% CI 52.5%, 74.5%] Yía тпv opáбa пou бléкoфe vs 51.3% [95% CI 35.6%, 67.0%] Yía тпv opáбa пou ouvéxíoe то abatacept). Ka^ avaЛoYÍa pe tov DAS28 Kaí o бeílкгnç HAQ-DI epфávloe plкpП eпlбeÍvwoп кaтá тп фáoп aпóoupoпç тou abatacept orouç аo9eveÍç пou éЛaßav placebo, п oпoÍа aкoЛoú9wç avaoтpáфпкe pe i^v eпaveloaYWYП тou фappáкou. H peЛéтп ATTUNE7 Птav pía avolx^ peЛéтп фáoпç IIIB пou oxeбláo9пкe Yía va eкпpПoel тпv aoфáЛela, тпv avoooY0vlкóтптa Kaí тпv aпoтeЛeopaтlкóтптa тпç aЛЛaYПç 9epaпeíaç aпó paкpoxpovÍwç X0PПY0Ú-pevo evбoфЛéßlo abatacept oe uto6ópio abatacept, oe аo9eveÍç pe peupaTOe^ ap9píтlбa. !тп peЛéтп evтáx9пкav 123 ao9eveÍç пou eíxav пбп Лáßel bv6o-фЛéßlo abatacept Yía тouЛáxloтo 4 xpóvía. EÇ arn"úv, по0о0т0 32% ßploкóтav oe úфeoп (DAS28-CRP<2,6) evú то 43.4% eíxe xapпЛП evepYÓтптa vóoou (DAS28-CRP<3,2) кaтá тпv évraft 0тп peЛéтп. Meтá aпó 12 pПveç 9epaпeíaç pe uпoбóplo abatacept oe бóoп 125mg/ eßбopáба тa пooooтá úфeoпç Kaí xapпЛПç evepYóтптaç vóoou бlaтпpП9пкav oe oтa9epá era-пeбa (39,8% úфeoп Kaí 51,3% xapпЛП evepYÓтптa vóoou). ЛÍY0 бlaфopeтlкá пapouoláZovтal та aro-тeЛéopaтa plaç plкpПç povoкevтplкПç peЛéтпç aпó тпv IтaЛÍa,13 o^v oпoÍa ouppeтeÍxav 51 ao9eveÍç pe peupaTOe^ ap9píтlбa пou peтaпПбпoav aró тпv evбoфЛéßla oтпv uпoбópla popфП тou abatacept. Лeкатéooepelç aпó auTOùç тouç ao9eveÍç (27,5%) Xpeláoтпкe va eпloтpéфouv oтпv evбoфЛéßla popфП X0pПYП0ПÇ, кaтá péoov ópo peтá aró 11 бóoelç тпç uпoбóplaç popфПç (eùpoç 5-30 бóoelç). Ze 13 TOpí-mùoelç п aЛЛaYП avaYKaía ЛÓYW éÇapoпç

тou vooПpaтoç ^£п0п тпç pé0пç тlpПç tou DAS28 oe 3.96 aró 2.19 кaтá тпv évapfti, p=0.002), evú oe éva ^plOTOn^ п бгаюопп Птav eпlßeßЛпpévп ЛóYw epфávloпç aveпl9úpптwv evepYeíúv (vauтía Kaí Ke-фaЛaЛYÍa). 'Exeí evбlaфépov va oпpelw9eÍ ón п plкpП

H КЛМКН XPHIIMOTHTA TOY YnOAOPIQI XOPHTOYMENOY ABATACEPT ITH 0ЕРАПЕ1А THI PEYMATOEIAOYI AP0PITAAI CUNiCAL USE OF SUBCUTANEOUS ABATACEPT iN THE TREATMENT OF RHEUMATOiD ARTHRiTiS

auTn MeAéTn nrav avaôpoMirai xwpÎQ npoKa9opioMévo opioMô TnQ é^aponQ. Anô touq ao9eveÎQ nou ené-oтpeфav oe evôoфЛéßlo abatacept, to 43% eixe xaMn-ЛП evepYôTnTa vôoou (DAS28<3,1), evw n ouммôpфw-on twv ao9evwv ôev кaтaYpâфnкe Kai ouvenwQ ôev YvwpiZouMe av n avâYKn aAAaYnQ oфelЛôтav oe napâ-Ae^n twv ôôoewv, éAAe^n eKnaiôeuonQ oTnv unoôô-pia xopnYnon П ioxupn npoTÎMnon tou ao9evoûQ oe evôoфЛéßla xopnYnon évavTi TnQ unoôôpiaQ. EninAé-ov, to nooooTô twv ao9evwv nou éЛaßav unoôôpio abatacept oe ouvôuaoMô Me Kânoio DMARD oe auTn Tn MeAéTn nrav MiKpôTepo anô ôti oTnv ACQUIRE4 (84% vs 99.6%) Kai oi ouYYPaфeÍQ ni9avoAoYoûv ôti auTô evôexoMévwQ ennpéaoe Ta anoTeAéoMaTâ touq. ZnMavTiKô eivai aKôMn ôti oi 13 anô touq ouvoÀiKâ 14 ao9eveÎQ nou eпéoтpeфav oTnv evôoфÀéßla мopфп xopnYnonQ rou abatacept ÇavaMnnrav oe ûфeon MeTâ anô 1 éwQ 2 evôoфЛéßleQ eYxûoeiQ tou фapмâкou, ye-YovôQ nou unoônAwvei ôti aKôMn Kai Mia anoTuxnMévn 9epaneuTiKn ôoKiMn Me unoôôpio abatacept ôev avai-pei Tnv aoфâЛela Kai Tnv anoTeAeoMaTiKôTnTa TnQ ev-ôoфЛéßlaQ мopфПQ.

H MeAéTn AMPLE8 napouoiâZei iôiaÎTepo evôlaфé-pov, Ka9wQ anoTeAei Mia anô tiq Aîyeq Méxpi oTiYMnQ ôia9éoiMeQ MeAéTeQ oûYKpionQ ôûo ßioAoYiKwv na-paYôvrwv MeTa^û touq. Ztôxoq nrav va ouYKpi9ei n xopnYnon unoôopiou abatacept 125mg^ôoMâôa Me unoôôpio adalimumab 40mg/ôûo eßôoмâôeQ oe ao9eveÎQ Me evepYô peuMaToeiôn ap9pÎTiôa, av9eKTi-koûq oTn 9epaneia Me Me9oTpeÇâTn Kai oi onoioi ôev eixav Çavanâpei aYwYn Me ßioAoYiKä фâpмaкa oto napeA9ôv. Ze auTnv Tnv noAuKevTpiKn, TuxaionoinMé-vn, npoonriKn, фâonQ lllb MeAéTn nou ouMnep^Aaße 646 ao9eveÎQ, to npwTapxiKô KaTaAnKTiKô onMeio nTav n anôKpion oTn 9epaneia KaTâ ACR20 otouq 12 MnveQ. Oi ao9eveÎQ Tuxaionoin9nKav oe avaAoYÎa 1:1 va Aâßouv évav anô touq ôûo пpoavaфep9évтeQ ßioAoYiKoüQ napâYovTeQ oe ouvôuaoMô Me oTa9epn ôôon Me9oTpe£;âTnQ15-25mg^ôoMâôa. Zto TéAoQ tou npwTou xpôvou, to nooooTô twv ao9evwv nou eмфâvloav avTanôKpion KaTâ ACR20 nrav 64.8% (95% CI 59.5%, 70.0%) oTnv oMâôa tou unoôopiou abatacept Kai 63.4% (95% CI 58.2%, 68.6%) oTnv oMâôa tou unoôopiou adalimumab. H EKTiMwMevn ôia-фopâ MeTaÇû twv 2 oMâôwv nTav 1.8% (95% CI 5.6%, 9.2%), KaTaôeiKvûovTaQ éToi Tn Mn KaTwTepôTnTa tou unoôopiou abatacept ev ouYKpioei npoQ to unoôôpio adalimumab. Omoîwq, ouYKpioiMa METa^û twv ôûo oMâôwv nTav otov éva xpôvo Kai Ta nooooTâ avra-nôKpionQ KaTâ ACR50 (46.2% [95% CI 40.7%,51.7%] vs 46% [95% CI 40.6%, 51.4%]) Kai ACR70 (29.2% [95% CI 24.2%, 34.2%] vs 26.2% [95% CI 21.5%, 31.0%] Yia touq ao9eveÎQ nou éAaßav unoôôpio abatacept Kai unoôôpio adalimumab, avTioToixwQ). H ßeATiwon tou ôeÎKTn DAS28-CRP oto éToQ nrav

2.30±0.08 Yia Tnv oMâôa tou unoôopiou abatacept Kai 2.27±0.08 (mean±SEM) Yia Tnv oMâôa tou unoôopiou adalimumab, evw ouYKpioiMa nrav Ta nooooTâ twv ao9evwv nou néTuxav ûфeon Kai xaMnAn evepYôTnTa vôoou Me ßâon auTô to ôeÎKTn. Qq npoQ Tn AeiToup-YiKn KaTâoTaon twv ao9evwv, ôev napaTnpn9nKe ôlaфopâ MeTaÇû twv ôûo oMâôwv oTn MeTaßoAn tou HAQ-DI otov éva xpôvo (Meiwon 0.60±0.04 Yia to unoôôpio abatacept Kai 0.59±0.03 [mean±SEM] Yia to unoôôpio adalimumab). Eivai onMavTiKô va avaфep9eí ôti oTn MeAéTn AMPLE n oMâôa tou abatacept Kai n oMâôa tou adalimumab ôe ô^epav oûTe wq npoQ to xpôvo évap^nQ rnQ ßeATiwonQ ôAwv twv napanâ-vw ôeiKTwv (ACR20, 50, 70, DAS28-CRPKai HAQ-DI). TéAoQ, avaфoplкâ Me Tnv aKTivoAoYiKn npôoôo tou voonMaToQ, n MeTaßoAn tou oAikoû TpononoinMévou Sharp/van der Heijde score nTav ouYKpioiMn otiq ôûo oMâôeQ, 0.58±3.22 (mean±SD) otouq ao9eveÎQ nou éAaßav unoôôpio abatacept, évavTi 0.38±5 otouq ao9eveÎQ nou éAaßav unoôôpio adalimumab, Me éva nooooTô 84.8% va eмфavíZel aKTivoAoYiKn oTaoiMô-TnTa oTnv npwTn oMâôa évavTi 88.6% oTn ôeûTepn (eKTiMwMevn ôlaфopâ 4.1% [95% CI 1.5%, 9.6%]). TéAoQ, n AVERT9 nTav Mia noAuKevTpiKn, Tuxaionoin-Mévn MeAéTn фâonQ lllb, ôiâpKeiaQ 24 Mnvwv, nou ne-plAâмßave Mia 12Mnvn nepioôo xopnYnonQ фapмâкou Me ôinAâ тuфAô oxeôiaoMô. Ztôxoq nTav va eKTiMn9ei n anoTeAeoMaTiKôTnTa tou unoôopiou abatacept, xopn-YoûMevou Môvou tou п oe ouvôuaoMô Me Me9oTpeÇâ-Tn, oTnv noAû npwiMn peuMaToeiôn ap9pÎTiôa, Ka9wQ Kai n iKavôTnTa TnQ Movo9epaneiaQ Kai tou ouvôua-omoû va ôiaTnpnoouv Tnv ûфeon otouq é^i MnveQ MeTâ Tn ôiaKonn xopnYnonQ aYwYnQ. Kpmipia évTa^nQ oTn MeAéTn anoTéAeoav - METa^û âAAwv - n enÎMovn na-pouoia ouMnTwMâTwv Yia xpoviKô ôiâoTnMa <2etwv, to DAS28-CRP>3.2 Kai n napouoia avTiowMâTwv KaTâ KiTpouAAivwMévwv nenTiôiwv. Oi ao9eveÎQ énpe-ne va Mnv éxouv Aâßel Me9oTpeÇâTn oto napeA9ôv П va éxouv Aâßel Yia ôiâoTnMa MiKpôTepo twv Teooâ-pwv eßôoмâôwv, evw oTa9epn énpene va napaMei-vei n ôôon rwv KopTiKoeiôwv oe ôoouq eAâмßavav. H MeAéTn ouмпepléAaße 351 ao9eveÎQ nou Tuxaionoi-n9nKav oe avaAoYÎa 1:1:1 va Aâßouv eÎTe unoôôpio abatacept 125mg^ôoMâôa wq Movo9epaneia, eÎTe unoôôpio abatacept 125mg/eßôoмâôа oe ouvôuaoMô Me Me9oTpeÇâTn, eÎTe Movo9epaneia Me Me9oTpeÇâTn oe ôôon 15-20mg/eßôoмâôa, Yia 12 MnveQ. 'Oooi ек twv ao9evwv néTuxav DAS28-CRP<3.2 oTnv npwTn фâon Mnopoûoav va eioéA9ouv oTn фâon anôouponQ twv фapмâкwv Yia touq enôMevouQ 12 MnveQ. MeTâ to 15o Mnva пpoßAeпôтav 9epaneia ôiâowonQ ме ouvôuaoMô unoôopiou abatacept Kai Me9oTpe^âTnQ av KânoioQ ao9evnQ éKave é^apon. Ztouq 12 MnveQ, o ouvôuaoMôQ tou unoôopiou abatacept ме me9o-Tpe^âTn фâvnкe nio anoTeAeoMaTiKôQ anô Tn Movo-

of RHEUMATOLOGY 2

e л л h n i к h рeymaтoлoгia 2015

9epaTOÍa pe pe9oтpe^áтп, pe 60.9% (70/115)iwv ao9evúv va epфavÍZouv DAS28-CRP<2.6 oтпv opá-бa тou ouvбuaopoú, évavn 45.2% (52/115) oтпv opá-бa тпç povo9epaпeÍaç (OR [95%CI] 2.01 [1.18,3.43], p=0.010). H povo9epaTOÍa pe uпoбóplo abatacept eíxe ouYкpÍolpп апoтeЛeopатlкóтпта 0т0 éva éTOç pe тп povo9epaTOÍa pe pe9oтpeÇáтп, Ka9^ 42.5% (48/113) тwv ao9evúv tou éЛaßav auтП тпv aYWYП p^Kav oe úфeoп. Zтouç 18 pПveç тa пooooтá тwv ao9evúv tou пapépevav oe úфeoп peтá m|v aráoup-0П тпç 9epaпeíaç Птav 14.8% (17/115) oтпv opáбa tou ouvбuaopoú Kaí 7.8% (9/115) o^v opáбa тпç povo9epaпeÍaç pe pe9oтpe^áтп (OR [95% CI] 2.51 [1.02,6.18], p=0.045). H povo9epaпeÍa pe uto6ópio abatacept бlатПpпoe 12.4% (14/113) тwv ao9evúv oe úфeoп oтouç 18 pПveç, пooooтó ouYKpíoípo pe eKeívo тпç povo9epaпeÍaç pe pe9oтpeÇáтп.

ß. Лебореуа АaфаЛeíаç

Тa бeбopéva aoфaЛeÍaç пou пeplЛapßávovтal onç пpoavaфep9eÍoeç peЛéтeç ouYкЛÍvouv 0т0 ón то uto6ópio abatacept апoтeЛeÍ pía páЛЛov aoфaЛП 9epaпeuтlкП eпlЛoYП peraft тwv бra9éolpwv ßloЛo-YíKúv пapaYóvтwv Yía тп peuparae^ ap9píтlбa. Oí Alten Kaí ouvepYáтeç14 ouYKévipwoav Kaí avéЛuoav та paKpoxpóvía бeбopéva aoфaЛeÍaç тou uto6opí-ou abatacept апó pía 61пЛп тuфЛП peЛéтп фáoпç IIa,3 6úo бlпЛéç тuфЛéç peЛéтeç фáoпç IIIb (ALLOW6 Kaí ACQUIRE4) Kaí 6úo avolxтoú oxeбlaopoú peЛéтeç, фáoпç IIIb (ACCOMPANY5 Kaí AТТUNE7). H aváЛuoп oupTOp^aße ouvoЛlкá 1879 ao9eveÍç pe 4214.6 ao9eveÍç-éтп éк9eoпç 0то oKeúaopa. Ze auтП тп ouYкevтpwтlкП aváЛuoп, п eпÍптwoп ooßapúv ave-пl9úpптwv evepYeíúv Птav 9.97 (95% CI 9.02-11.02) Kaí aфopoúoe кupíwç е^пЛ^ею aпó то puoo^e-rnó Kaí Ло^^е^. H eпÍптwoп ooßapúv Ло^^е-wv Птav 1.79 (95% CI, 1.42-2.24) pe rao ouxvП rniv пveupovÍa, тпv oupoЛoÍpw^п Kaí тп YaoтpevтepÍтlбa. Тa пeploтaтlкá фupaтÍwoпç Птav oпávla, pe eramw-0П 0.09 (95% CI, 0.04-0.25). H eпÍптwoп Kaw^eraç Птav 1.32 (95% CI 1.01-1.72) pe пю ouxvoûç тouç oupпaYeÍç óYкouç, evú тa auTOávooa oupßápaтa eíxav eпÍптwoп 1.37 (95% CI 1.06-1.78), pe пю ou-XvП тпv epфávloп фwpÍaoпç Kaí ouv6pópou Sjögren. ZuvoЛlкá oпpelú9пкav 25 9ávaтol (eпÍптwoп 0.59 [95% CI 0.40-0.88]), eK тwv oпoÍwv 7 ouoxeтÍo9пкav пl9avúç п pe ßeßaютnта pe то oKeúaopa. Oí TOraKéç avтlбpáoelç 0т0 oпpeÍo тпç éveoпç Птav apкeтá oпá-vleç, пп^ Kaí кaЛúç avenreç Kaí ouvП9wç eЛápßa-vav xúpa péoa oto пpúтo eÇápпvo aпó тпv évapft тпç aYWYПç. Aпó pía aváЛuoп uпoopáбwv бlaпloтú-9пкe órn ao9eve^ пou eíxav xapпЛóтepo owpaтlкó ßápoç (<100Kg) Kaí plкpóтepп пЛlкÍa (<65 ётп) кaтá тпv évapfti ^ç 9epaпeíaç pe uпoбóplo abatacept eíxav plкpóтepп пl9avóтптa epфávloпç aveпl9úpп-

тwv evepYeíúv. ZuvoЛlкá, то пpoфÍЛ aoфaЛeÍaç тou uпoбopÍou abatacept фаíveтаl ón eívaí ouYKpíoípo pe auтó tou evбoфЛeßÍou oкeuáopaтoç, óпwç пpoкúптel aró тпv avтlпapaßoЛП тwv бeбopévwv ^ç aváЛuoпç тwv Alten Kaí ouvepYaiúv pe тa бeбopéva plaç пa-Лalóтepпç, avтÍoтolxпÇ ouYкevтpwтlкПç aváЛuoпç, П oпoÍa oupTOp^aße 4149 ao9eveÍç pe peupaTOe^ ap9píтlбa пou éЛaßav evбoфЛéßlo abatacept ouve-Xúç, Yía péxpí Kaí 7 ётп.15

Тa aпoтeЛéopaтa тпç AMPLE8 Kaí тпç AVERT,9 6úo пoЛuкevтplкúv, тuxaloпolПpévwv peЛeтúv tou 6bv пeplЛapßávovтal oтпv aváЛuoп тwv Alten Kaí ouvep-Yaтúv, eпÍoпç evíoxúouv тпv áпoфп ón то uto6ó-pío abatacept бra9éтel éva páЛЛov euvoiKó пpoфÍЛ aoфaЛeÍaç. H AMPLE,8 tou óпwç пpoavaфép9пкe ouvéKpíve то uпoбóplo abatacept pe то uto6ópio adalimumab oe пЛп9uopó 646 ao9evúv pe peupa-тоейп ap9píтlбa, кaтéЛп^e 0т0 oupпépaopa ón та XapalкгnPloтlкá aoфaЛeÍaç тwv 6úo ßloЛoYlкúv пa-paYóvтwv Птav ouYKpíoípa. Zoßapéç aveпl9úpптeç evépYeleç epфavÍoтпкav 0т0 10.1% тwv ao9evúv uпó uпoбóplo abatacept, évavn 9.1% тwv ao9evúv uto uto6ópio adalimumab. Пooooтó 1.3% óowv eЛápßа-vav uпoбóplo abatacept аvаYкáoтпкаv va бlaкóфouv то фáppaкo ЛóYw ooßapúv aveпl9úpптwv evepYeíúv, évavn 3% o^v opáбa тou uпoбopÍou adalimumab. OpoÍwç, ouYKpíoípa peraft тwv 6úo opáбwv Птav тa пooooтá epфávloпç ooßapúv ЛolpúÇewv (2.2% oтпv opáбa тou sc abatacept, évavn 2.7% o^v opáбa тou sc adalimumab), какoп9elúv (1.6% oтпv opáбa tou sc abatacept, évavn 1.2% o^v opáбa тou sc adalimumab) Kaí auтoávoowv oupßávтwv (3.1% oтпv opáбa тou sc abatacept, évavn 1.2% o^v opáбa тou sc adalimumab). Qotooo, апó тouç 9 ao9eve^ пou epфávloav ooßapП ЛoÍpw^п oi^v opáбa тou uto6opí-ou adalimumab, oí 5 аvаYкáoтпкаv va бlaкóфouv тпv aYWYП, evú Kapía бгагапп ЛóYw ooßapПç ЛoÍpw^пç 6b oпpelú9пкe oтпv opáбa тou abatacept. ТéЛoç, 0П-pavnKá ЛlYóтepol ao9eveÍç o^v opáбa тou uto6opí-ou abatacept epфávloаv топип avтÍбpaoп 0то oпpeÍo тпç éveoпç (3.8% oтпv opáбa тou sc abatacept, évavn 9.1% o^v opáбa тou sc adalimumab, p=0.006). Та бeбopéva aoфaЛeÍaç Yía то uпoбóplo abatacept tou пpoépxovтаl aпó тп peЛéтп AVERT,9 eívaí eпÍoпç ev9appuvnKá. Zoßapéç aveпl9úpптeç evépYeleç eK-бпЛú9пкav oe 12.1%, 6.7% Kaí 7.8% óowv eЛápßa-vav povo9epaпeÍa pe uпoбóplo abatacept, ouvбuаopó uпoбopÍou abatacept pe pe9oтpeÇáтn Kaí povo9epa-пeía pe pe9oтpeÇáтn, avтÍoтolxa. Zoßapéç Ло^^е^ epфávloe то 3.4%, 0.8% Kaí 0% тwv ao9evúv avrí-oтolxa, evú oe бгагапп тпç aYWYПç ЛÓYW ooßapПç aveпl9úpптпç evépYelaç пpoxúpпoe то 4.3%, 1.7% Kaí 2.6% тwv ao9evúv oe Ká9e opáбa, avтloтoÍxwç.

H KANIKH XPHIIMOTHTA TOY YnOAOPIQI XOPHTOYMENOY ABATACEPT ITH 0ЕРАПЕ1А THI PEYMATOEIAOYIAP0PITIAAI CLiNiCAL USE OF SUBCUTANEOUS ABATACEPT iN THE TREATMENT OF RHEUMATOiD ARTHRiTiS

y. AvoooyoviKoxnTa тои unoööpiou Abatacept

ZnMavTiKn ouvioTwoa TnQ aoфâAelaQ twv ßioAoYiKwv napaYôvTwv anoTeAei n avoooYoviKôTnTâ touq, Ka9wQ o oxnMaTioMôQ avTiowMâTwv évavTi twv Mopiwv auTwv ouvoôeûeTai ouxvâ anô anwAeia TnQ anoTeAeoMaTi-KôTnTâQ touq Kai anô eмфâvlon aveni9ûMnrwv evep-Yeiwv. Ze TpeÎQ anô tiq пpoavaфep9eíoeQ MeAéTEQ, oTnv ACCOMPANY,5 Tnv ALLOW6 Kai Tnv ATTUNE,7 n avoooYoviKôTnTa tou unoôopiou abatacept anoTé-Aeoe npwTapxiKô KaTaAnKTiKô onMeio. ZTnv avoixToû oxeôiaoMoû MeAéTn ACCOMPANY,5 n xopnYnon sc abatacept Yia ôiâoTnMa 4 Mnvwv, eîte oe ouvôuaoMô Me Me9oTpeÇâTn П xwpÎQ, npoKâAeoe Tnv napoôiKn eмфâvlon avTiowMâTwv KaTâ tou фapмâкou oe 3.9% twv ao9evwv oTnv oMâôa tou ouvôuaoMoû ме me9o-Tpe^âTn Kai oe 4.1% twv ao9evwv oTnv oMâôa TnQ Movo9epaneiaQ. OuôeÎQ ек twv ao9evwv napéMeive 9etikôq Yia avTiowMaTa KaTâ tov TéTapTo Mnva. ZTn фâon enéKTaonQ TnQ MeAéTnQ Môvo oe évav ao9evn (1.1%) ôianioTw9nKe avoooYoviKôTnTa tou unoôopiou abatacept. ZuMnepaoMaTiKâ, n avoooYoviKôTnTa tou unoôopiou abatacept eivai xaMnAn Kai ôev enn-peâZeTai anô Tn ouYxopnYnon П Mn Me9oTpeÇâTnQ. ZTn ôinAn тuфAп, TuxaionoinMévn MeAéTn ALLOW6 n ôiaKonn TnQ xopnYnonQ sc abatacept Yia 12 eßôoмâ-ôeq Kai n enavévapÇn rnQ, фâvnкe va npoKaAei Mia Mn oTaTioTiKâ onMavTiKn aûÇnon TnQ avoooYoviKôTn-TaQ tou oKeuâoMaToQ KaTâ Tn фâon anôouponQ (7/73 ao9eveÎQ eixav avTiowMaTa oTnv oMâôa nou ôléкoфe évavTi 0/38 oTnv oMâôa nou ouvéxioe to abatacept, p=0.119), nou аveoтpâфn ме Tnv enavévapÇn rnQ 9e-paneiaQ (2/73 ao9eveÎQ ме avTiowMaTa oTnv oMâôa nou ôléкoфe évavTi 1/38 oTnv oMâôa nou ouvéxioe to abatacept). KaTâ ouvéneia Kai auTn n MeAéTn TEKMnpi-wvei ôti n avoooYoviKôTnTa tou unoôopiou abatacept eivai MiKpn Kai ôev ennpeâZeTai anô Mia ßpaxuxpô-via ôiaKonn oTn Aпфn tou oKeuâoMaToQ. EninAéov, n avoixToû oxeôiaoMoû MeAéTn ATTUNE,7 oTnv onoia ao9eveÎQ nou eAâмßavav MaKpoxpoviwQ evôoфAé-ßio abatacept âAAaÇav oe unoôôpia мopфп xopnYnonQ, aпoкâAuфe ôti n aAAaYn auTn eixe noAû MiKpéQ eninTwoeiQ oTnv avoooYoviKôTnTa tou фapмâкou. Ztouq TpeiQ MnveQ Môvo 8 anô touq 123, ouvoAiKâ, ao9eveÎQ ßpé9nкav opo9eTiKoi Yia avTiowMaTa évavTi tou nAnpouQ Mopiou П rou CTLA4 TMnMaToQ tou abatacept, ек twv oi 6 eixav YvwoTâ avTiowMaTa Kai npiv Tnv aAAaYn oe unoôôpio oKeûaoMa. EninAéov oe 6/8 auToûQ ao9eveÎQ n кЛмкП anoTeAeoMaTiKôTnTa tou unoôopiou abatacept ôiaTnpn9nKe Kai Môvo oe 2 napaTnpn9nKe eniôeivwon. TéAoQ, n ôinAâ тuфAп, TuxaionoinMévn MeAéTn ACQUIRE4 oTa nAaioia TnQ onoiaQ enionQ eÇeTâo9nKe n avoooYoviKôTnTa, ôev éôeiÇe ôlaфopâ tou unoôôpiou oe oxéon ме to evôo-фAéßlo abatacept (avTiowMaTa avixveû9nKav oe 1,1% vs. 2.2% twv ao9evwv otiq ôûo oMâôeQ avTÎoToixa).

ZnMeiwTéov n napouoia avTiowMâTwv oe auToûQ touq ao9eveÎQ ôe фâvnкe va ennpeâZei Tnv aoфâAela Kai Tnv anoTeAeoMaTiKôTnTa tou oKeuâoMaToQ.

IYZHTHIH

napôTi oi ßioAoYiKoi napâYovTEQ Yia Tn 9epaneia TnQ peuMaToeiôoûQ ap9pÎTiôaQ eivai onMepa nepiooôTepoi anô noTé, n eniAoYn rou KaTaAAnAôTepou oKeuâoMaToQ Yia tov Kâ9e ao9evn eÇaKoAou9ei va Ka9opiZeTai oe MEYâAo ßa9мô EMneipiKâ. H oeipâ ме Tnv onoia oi ßioAoYiKoi napâYovTEQ KaTéoTnoav ôia9éoiMoi, ôia-MopфWvel Tnv EMneipia MaQ oTn xpnon touq Kai nai-Zei onMavTiKô pôAo oTnv eniAoYn rou evôq évavTi tou âAAou. Auotuxwq, n KaTavônon TnQ пa9oфuoloAoYÍaQ tou voonMaToQ ôev eniTpénei aKôMn rnv e^aToMiKeu-Mévn xpnon rwv фapмâкwv ме ßâon to MnxavioMô ôpâonQ touq. E^âAAou, Ta ôeôoMéva oûYKpionQ METa-Çû ôûo П nepioooTépwv ßioAoYiKwv napaYôvTwv eivai Méxpi oTiYMnQ AÎYa,8'16'17 evw môAiq пpôoфaтa Kânoia ßloAoYlкâ фâpмaкa nnpav éYKpion va xpnoiMonoioû-vTai wq aYwYn npwTnQ YpaMMnQ.1 Ze auTâ Ta nAaioia, Mia anô tiq onMavTiKôTepeQ napaMéTpouQ nou Ka9o-piZouv Tnv eniAoYn ßioAoYiKo! napâYovTa napaMévei n oôôq xopnYnonQ rou фapмâкou. Aev npénei va na-paYvwpiZeTai n onMaoia TnQ oôoû xopnYnonQ rôoo Yia Tnv noiôTnTa ZwnQ tou ao9evoûQ, ôoo Kai Yia to kôotoq TnQ 9epaneiaQ, aAAâ Kai Yia Tnv npooßao^-TnTa tou ao9evoûQ oto фâpмaкo, eiôiKâ oe Mia xwpa ônwQ n ôiKn MaQ ме touq YewYpaфlкoûQ nepiopioMoûQ nou ouvenâYETai to nAn9oQ twv anoMovwMévwv vn-oiwtikwv Kai opeivwv oikiomwv. To abatacept eivai o npwTOQ ßloAoYlкôQ napâYovTaQ Yia Tn peuMaToeiôn ap9pÎTiôa nou KaTéoTn ôia9éoiMoQ Tôoo wq evôoфAé-ßio, ôoo Kai wq unoôôpio oKeûaoMa Kai auTô avaмфí-ßoAa ôivei nepiooôTepeQ ôuvaTôTnTEQ oto 9epânovTa va eÇaToMiKeûoei Tnv aYwYn.

Ooov aфopâ oTnv npoTÎMnon twv ao9evwv oxeTiKâ ME Tnv oôô xopnYnonQ rwv ßioAoYiKwv napaYôvTwv oi yvwmeq eivai MoipaoMéveQ. Ze Mia пpôoфaтn lTa-AiKn MeAéTn18 802 ao9eveÎQ ме peuMaToeiôn ap9pÎTi-ôa, nou ôev eixav Aâßel noTé anti-TNF-a napâYovTa, pwTn9nKav Yia Tnv npoTiMwMevn oôô xopnYnonQ rou фapмâкou. KaTâ evôlaфépovтa Tpôno, to 50,2% ené-AeÇe Tnv evôoфAéßla oôô, evw to 49,8% Tnv unoôôpia oôô xopnYnonQ rou anti-TNF-a. To aio9nMa aoфâAel-aQ nou ônMioupYei n napouoia tou iaTpoû KaTâ Tnv evôoфAéßlo xopnYnon nrav Ka9opioTiKôQ napâYovTaQ oTnv npwTn nepinTwon, evw n MEYaAûTepn eueAiÇia Kai n ôuvaTôTnTa napaMovnQ oto onÎTi énaiZe onMavTiKô pôAo oTn ôeûTepn eniAoYn.

napôTi ôev unâpxouv aKôMn enapKn KAiviKâ ôeôoMéva anô MaKpoxpôvia éK9eon oto unoôôpio abatacept, Ta eupnMaTa TnQ ACQUIRE4 Kai n ouYKevTpwTiKn avâAuon twv ôeôoMévwv aoфaAeíaQ 5 meAetwv anô

of RHEUMATOLOGY 2

eaahnikh peymatqaoria 2015

touq Alten Kai ouvepYáTeQ,14 éSei^av óti to unoSó-pio abatacept éxei ouYKpíoipo npo0íÁ ao<J>áÁeiaQ Kai anoTeÁeopaTiKóTnTaQ pe to evSo0ÁéPio oKeúaopa. Iúp0wva pe Tn peÁéTn ATTUNE,7 n aÁÁaYñ anó Tnv evSo0ÁéPio pop0ñ xopñYnonQ oTnv unoSópio pop0ñ eívai pia ao0aÁñQ eniÁoYñ, nou ouvoSeúeTai anó Si-aTnpnon TnQ anoTeÁeopaTiKóTnTaQ tou 0appáKou. AKópn ópwQ Kai oe nepírnwon é^aponQ TnQ vóoou peTá Tnv aAAaYñ oto unoSópio oKeúaopa, n ena-va0opá TnQ ev6o0ÁéPiaQ xopñYnonQ eívai enapraíQ Yia va anoKaTaoTiíoei tov éÁeYxo tou vooñpaToQ, ónwQ éSeift pía piKpñ, ave^ápTnTn peAéTn anó Tnv iTaAía.13 iTn ouv|9n KÁiviKñ npaiKTiKñ, npoTeíveTai n xopiYnon píaQ evSo0ÁéPiaQ SóonQ 0ópTionQ tou abatacept, npiv Tnv évapfti tou unoSopíou oKeuá-opaToQ. OnwQ ópwQ éSei^av Ta SeSopéva TnQ pe-AéTnQ ACCOMPANY aAAá Kai TnQ peÁéTnQ AMPLE, otiq onoíeQ Sev nponYñ9nKe evSo0ÁéPia 0ópTion, n napáÁei^n auToú tou PñpaToQ Sev ennpeáZei Tnv anoTeÁeopaTiKóTnTa. EníonQ, n npoowpivñ SiaKonñ TnQ xopñYnonQ unoSopíou abatacept pe enavévap-ft TnQ aY^YÍQ peTá anó xpoviKó SiáoTnpa 3 pnvúv, napóTi ouvoSeúTnKe anó napoSiKñ peíwon TnQ anoTeÁeopaTiKóTnTaQ Kai aúftion TnQ avoooYoviKóTnTaQ tou 0appáKou KaTá Tn 0áon anóouponQ, Se 0ávn-Ke va éxei TeÁiKá eninTúoeiQ oTnv ao0áÁeia Kai Tnv anoTeÁeopaTiKóTnTa tou oKeuáopaToQ, Ka9óoov n apxiKñ eniSeívwon avaoTpá<J>nKe peTá Tnv enavévap-ft TnQ aY^YÍQ.6 ^Q npoQ Tnv anoTeÁeopaTiKóTnTa tou unoSopíou abatacept óTav auTó xpnoiponoieÍTai wq povo9epaneía ñ oe ouvSuaopó pe pe9oTpe£áTn, n peÁéTn ACCOMPANY5 éSeift óti otouq 4 p|veQ n PeÁTíwon ñTav ouYKpíoipn otiq Súo opáSeQ. BéPaia, oTn 0áon enéKTaonQ auT|Q TnQ peÁéTnQ xpeiáoTnKe va npooTe9eí pe9oTpe£áTn oto 23.3% twv ao9evúv nou eÁápPavav apxiKá povo9epaneía, npoKeipévou va SiaTnpñoouv Tnv ú0eoñ touq. EninÁéov n peÁéTn AVERT,9 nou SievepYñ9nKe oe ao9eveíQ pe noÁú npú-ipn peupaToeiSñ ap9píTiSa Kai eíxe Tpía 9epaneuTiKá oKéÁn: povo9epaneía pe unoSópio abatacept, ouvSuaopó unoSopíou abatacept pe pe9oTpe£áTn Kai povo-9epaneía pe pe9oTpe£áTn, éSeift oa0ñ unepoxñ tou ouvSuaopoú oe oxéon pe tiq povo9epaneíeQ. TéÁoQ, iSiaíTepo evSia^épov napouoiáZouv Ta anoTeÁéopa-Ta TnQ ápeonQ oúYKpionQ tou unoSopíou abatacept pe to unoSópio adalimumab oTn peÁéTn AMPLE,8 anó Tnv onoía npoKúnTei óti oi Súo Pioáoyikoí napáYovTeQ Se Sia0épouv wq npoQ Tnv anoTeÁeopaTiKóTnTa, to xpóvo évap^nQ TnQ SpáonQ touq, Kai Tnv ao0áÁeiá touq, pe to abatacept va unepTepeí wq npoQ Tnv ep-0ávion ÁiYóTepwv ToniKúv avTiSpáoewv oto onpeío TnQ éveonQ.

ZYMnEPAZMATA

^Tnv napoúoa epYaoía avaoKonoúvTai Ta SeSopéva ao0aÁeíaQ Kai anoTeÁeopaTiKóTnTaQ tou unoSopíou abatacept, evóQ Pioáoyikoú napáYovTa nou oTnv evSo^ÁéPia pop0ñ xopñYnonQ KaTéxei |Sn onpavTi-kó póÁo oTn 9epaneuTiK| TnQ peupaToeiSoúQ ap9pí-TiSaQ. napóTi o xpóvoQ éK9eonQ twv ao9evúv oto unoSópio abatacept eívai aKópn PpaxúQ, Ta anoTe-ÁéopaTa anó tiq Sia9éoipeQ peÁéTeQ Seíxvouv óti to unoSópio oKeúaopa eívai ouYKpíoipo pe to evSo0Áé-Pio wq npoQ Tnv iKavóTnTá tou va npoKaÁeí ú0eon, va PeÁTiúvei touq ÁeiToupYiKoúQ SeíKTeQ twv ao9evúv Kai va avaoTéÁÁei Tnv aKTivoÁoYiKñ eftÁift TnQ peupaToeiSoúQ ap9píTiSaQ, evú peÁéTeQ oúYKpionQ Seí-xvouv óti eívai e^íoou anoTeÁeopaTiKó Kai pe to unoSópio adalimumab. EninÁéov, ónwQ Kai to evSo0ÁéPio oKeúaopa, to unoSópio abatacept anoTeÁeí pia páÁ-Áov ao0aÁ| 9epaneuTiK| eniÁoYñ. H npóo0aTa Sia-9éoipn SuvaTóTnTa xopñYnonQ tou abatacept eíTe wq evSo^ÁePíou eíTe wq unoSopíou oKeuáopaToQ, éxei iSiaíTepn onpaoía Yia touq peupaToÁóYouQ Kai touq ao9eveíQ touq, a0oú au^ávei Tnv eueÁi^ía otov Ka9o-piopó TnQ 9epaneuTiK|Q aYWYñQ Kai napioTá pía eu-npóoSe^n Áúon Yia touq ao9eveíQ eKeívouQ nou Se 9éÁouv ñ Se pnopoúv va ÁáPouv evSo0ÁéPio aYWYñ.

H КЛМШ XPHIIMOTHTA TOY УПОЛОРЮ! XOPHTOYMENOY ABATACEPT ITH QEPAnEIA THI PEYMATOEIAOYI APQPITIAAI CLiNiCAL USE OF SUBCUTANEOUS ABATACEPT iN THE TREATMENT OF RHEUMATOiD ARTHRiTiS

BißAioypa0ia

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