Ehlotyeni ka-2017, abaphandi babika ngeziphumo ezivela kwilingo leCANTOS, apho unyango kunye nesicatshulwa esichaphazelayo canakinumab (Illaris, Novartis) banciphise kakhulu umngcipheko weziganeko ezinkulu zenhliziyo kubantu ababesengozini enkulu.
Uninzi lweengcali zikholelwa ukuba iCANTOS izakukhunjulwa njengolu vavanyo oluphawulekayo, kuba luyilo lokuqala lonyango oluqinileyo lokuba unyango lweziyobisi olujoliswe ngokukodwa ekunciphiseni ukuvutha kunokuphucula iziphumo zengqondo.
Ukuchonga ukuvuvukala njengenjongo entsha yokunyanga ukukhusela ngokuqinisekileyo kuyisizathu sokuba nethemba, kwaye sinokulindela inani elikhulu lophando ngoku olujoliswe kulolu hlobo. Nangona kunjalo, simele sibe nokungathemba ukuba isilwanyana esithile esetyenziswe kwiCANTOS-trial canakinumab-iya kuba yinto ekhethiweyo yokonyango kubantu abasengozini enkulu ye-cardiovascular.
Ukuvutha kunye ne-Atherosclerosis
Kuye kwaziwa ngamashumi eminyaka ukuba ukuvuvukala kudlala indima kwi- atherosclerosis , kwaye ngokukodwa, iiseli ezivuthayo ziyinxalenye ephawulekayo yeenatrosclerotic plaques. Kuloo macwecwe, i- macrophage (uhlobo lweseli elimhlophe legazi) elithathile i- LDL ye-cholesterol ene-oxidizedi ekhupha izinto ezininzi ezivuthayo, ezibangela ukuvuvukala. Kukholelwa iminyaka kangangokuba ukuvuvukala kukunceda ekukholeni ukutywala kunye nokuqhekeka kwepenca. Ukuqhekeka kweplate kunokubulala. Ukuphuka kwe-Plaque ngokuqhelekileyo isiganeko ekugqibeleni eshukumisa i -coronary syndrome enzima , ekhokelela ekungeneni okungaqinisekiyo okanye ekuhlaselweni kwentliziyo .
Kukho ubungqina bezilingo zeklinikhi ezibonisa ngokucacileyo ukuba ukuvuvukala kubalulekile ekuqaliseni isiphumo somntu nge-atherosclerosis. Ngokukodwa, amanqanaba egazi aphakamileyo amachibi amabini okuvuvukala- Iprotheyini esebenzayo e-C kunye ne-interleukin-6-inxulumene nobungozi bokuhlaselwa kweentliziyo, kunye nezinye iziganeko zentliziyo.
Ukongezelela, uphando lubonise ukuba izidakamizwa ze-statin-ezo ziyaziwayo ngokunciphisa amazinga e-cholesterol, kodwa eziye zinciphisa ukuvutha-ziphumelela ekuphuculeni iziphumo zeeklinikhi zabantu abaphezulu abasemgangathweni abantu abanamazinga aphezulu e-CRP, nangona iinqwelo zabo ze-cholesterol zingakhange ziphakanyiswe. (Iingcali ezininzi zikholelwa ukuba kuba ama-statins enza okungaphezulu "nje" ekunciphiseni i-cholesterol eyenza ukuba isebenze ngokukodwa ekunciphiseni ingozi ye-cardiovascular risk. Funda malunga nento eyenza ama-statins "ahluke." )
Nangona kunjalo, kwaze kwaba yilapho ityala likaCANTOS lingekho, akukho uphando lwezonyango oluye lwaboniswa ukuba ukunciphisa ukuvutha kwamathambo, ngaphandle kokunciphisa amanqanaba e-cholesterol, kuya kuphucula iziphumo zeklinikhi.
Triant CANTOS
Isilingo seCANTOS sasebenzisa inkunkuma ekhethekileyo ejolise kwicandelo elithile leempendulo ezivuthayo. I-Canakinumab yi-anti-monoglonal antibody enqanda i-interleukin-1b, i- cytokine ebaluleke kakhulu endleleni yokuvuvukala ehlobene ne-interleukin-6. I-Canakinumab ivunyiwe iminyaka emininzi kunyango lweengxaki ezithile ze-rheumatologic, kodwa yayingazange isetyenziswe ukuphatha isifo senhliziyo.
Kwilingo leCANTOS, abantu abangaphezu kwe-10 000 abaye basinda ekuhlaselweni kwentliziyo, kunye nabaphakamisa amanqanaba egazi le-CRP, babengenakulinganiswa ukuba bafumane i-injections ye-canakinumab okanye indawo ye-placebo.
Emva kweminyaka engama-3.7 yokulandelelana, abantu abaye bafumana i-injakumumab engama-150 mg (kodwa kungekhona abo bafumana ama-50 mg okanye 300 mg) banomngcipheko wokunciphisa umngcipheko weemeko zengqondo (njengoko zilinganiswe ngumbono wokugqibela equkethe ukuhlaselwa yintliziyo engabulaliyo, isifo esibulalayo, okanye ukufa kwesifo senhliziyo). Ukufa okuqhelekileyo akuzange kuthinteke yi-canakinumab.
Inzuzo ezuzwe ngama-injini engama-150 mg, ngelixa kubalwa inani elilinganiselweyo, lalilingakanani elincinci, kwaye kubaluleke kakhulu kwiiklinikhi ezingundoqo. Kwiqela le-placebo, kwakukho iziganeko zeklinikhi ezingama-100 ngeminyaka-100 yabantu, vs vs 3.86 iziganeko kwi-100 yabantu-iminyaka kubantu abafumana 150 mg canakinumab.
Ngamanye amazwi, ukunciphisa ngokupheleleyo umngcipheko kwindawo yokufunda kwakungaphantsi kwama-1 ekhulwini emva kweminyaka emine yonyango. Nangona le nqanaba lenzuzo ayinangqangi kakhulu, yayisabonakaliswa ngokubaluleka. Ngaloo ndlela, iziphumo zetyala leCANTOS zibonisa ngokucacileyo, ngokokuqala ngqa, ukuba unyango oluchasayo lunokuphucula iziphumo zentliziyo yomzimba kubantu abasengozini enkulu.
Kubalulekile ukuxininisa kwakhona ukuba i-canakinumab ayiyiyo i-mill-the-mill-anti-inflammatory drug. Esikhundleni salo, ijoliswe kwindawo ethile kunye neyodwa kwi-cascade evuthayo. Akucaci ukuba iziyobisi ezichaphazela ezinye iinkalo zokuvuvuka ziya kuba luncedo. Enyanisweni, kuyaziwa ukuba izidakamizwa ezingekho-steroidal ezichasayo (i-NSAIDS) zibonakala zibuhlungu kakhulu. Ngoko, inzuzo ebonakalayo ye-cardiovascular eyeboniswe nge-canakinumab ayisebenzisi kwezinye iziyobisi ezichasayo.
Njengengxelo yecala, abantu kwi-CANTOS ilingo abafumana i-canakinumab babonwa ukuba banomngcipheko wokufa ngenxa yomdlavuza wamaphaphu-enye imeko apho ukuvutha kucingelwa ukuba kudla indima ebalulekileyo. Ngoko ityala leCANTOS livule indlela entsha yophando malunga nokuvuvukala nomhlaza.
Isiganeko esibi esibonakalayo kunye ne-canakinumab kwilingo leCANTOS yinkwenkwe encinci kodwa ephawulekayo ekufeni ngenxa yezifo. Ekubeni impendulo enamandla yokuvutha ivame ukuyimfuneko ekukhuseleni izifo, ukufumana oku akuzange kumangalise.
Konke oku kuthetha
Akungabazeki ukuba isilingo seCANTOS siya kukhokelela ekusebenziseni jikelele kwe-canakinumab ukwenzela ukunciphisa imicimbi ye-cardiovascular kubantu abasengozini enkulu. Akunakwenzeka nje kuphela ukuba inzuzo yeklinikhi evela kwi-canakinumab ibonakala ihle kakhulu, kodwa kwakhona le nkunkuma ibiza kakhulu. Unyango lwangoku kunye ne-canakinumab, kubantu abaneengxaki ze-rheumatologicalic, zibiza ngee- $ 200,000 ngonyaka. Isisindo esifanelekileyo senzuzo ye-cardiovascular esiboniswe kwilingo leCANTOS ngokuqinisekileyo ayiyi kuqikelela ukusetyenziswa kwezidakamizwa ezibiza.
Ngoko ke, ngokubalulekileyo, ukubaluleka kokufundwa kweCANTOS akukona ukuba kuye kwafumanisa unyango olutsha lokukhusela isifo senhliziyo, kodwa kunoko, ukuba lufumene ithagethi entsha yophando.
Kuze kube ngoku, ukunciphisa umngcipheko we-cardiovascular ngeyeza kuncitshiswa kakhulu kwi-cholesterol yehla (ikakhulukazi kunye nama-statins), kwaye mhlawumbi inqanda i- thrombosis (kunye ne- aspirin ). Ngoku ibonakala, ngokucacileyo ngakumbi kunanini ngaphambili, ukuba kugxininisa imiba ethile yempendulo evuthayo kwimithambo yegazi inokunciphisa iziganeko zeentlekele zenhliziyo.
Sinokulindela ukuba iinkampani zokuxuba imveliso zisebenzise ngokukhawuleza le ndlela entsha yokwenza unyango, kwaye zinyusa kakhulu ukuphuhliswa kwazo ezinye iizithunywa ezinokunciphisa ukuvutha kwamathambo. Ukuba le nzame ikhupha nantoni na enjengezinto ezininzi iingcali eziye zixela kwangaphambili, isilingo seCANTOS ekugqibeleni siza kuthathwa njengento ebonakalayo ekwenzeni unyango lwe-cardiovascular-whether it is not the use of canakinumab ngokwayo.
ILizwi
Ngoku kubonakala ngokuqinisekileyo ukuba ukuvuvukala kudlala indima enkulu ekuphuhlisweni kwe-atherosclerosis, kunye nasiphumo sabantu abane-atherosclerotic vascular disease. Icandelo le-CANTOS liye labonisa ukuba unyango olujoliswe kwiinkalo ezithile zempendulo ezivuthayo zingaphucula kakhulu umphumo wabantu abasengozini enkulu.
Nangona i-canakinumab-isilwanyana esiqashwe kwi-CANTOS-esingaze sisebenzise ngokubanzi isifo se-cardiovascular, abaphandi baye baqalisa indlela entsha yokunyangwa kwesi sifo. Kwiminyaka ezayo singalindela ukuva okungakumbi malunga nokuvuvukala njengesibangeleko se-atherosclerosis, kunye neendlela ezintsha zokwelapha ezijoliswe ekunciphiseni ukuvutha.
> Imithombo:
> Libby P, Ridker PM, uHansson GK, uLeducq Transatlantic Network kwi-Atherothrombosis. Ukuvuvukala kwi-Atherosclerosis: Ukususela kwi-Pathophysiology ukuya kuSebenza. J Am Coll Cardiol 2009; 54: 2129.
> Ridker PM, uEvarett BM, uTyren T, et al. I-Anti-inflammatory Therapy ne Canakinumab ye-Atherosclerotic Disease. N Engl J Med 2017; INGXELO: 10.1056 / NEJMoa1707914.
> Weber C, iiNelsel H. I-Atherosclerosis: I-Pathogenesis yangoku kunye neendlela zokwelapha. Nat Med 2011; 17: 1410.