Ehlobo lika-2017, abaphenyo babika ngemiphumela yecala le-CANTOS, lapho ukwelashwa nge-anti-inflammatory drug canakinumab (Illaris, Novartis) kunciphisa kakhulu ingozi yemicimbi emikhulu yezinhliziyo kubantu abasengozini enkulu.
Ochwepheshe abaningi bakholelwa ukuthi i-CANTOS izokhunjulwa njengesilingo esibucayi, ngoba siwubufakazi bokuqala obuqinile bokuthi ukwelashwa kwezidakamizwa okuhloswe ngokukhethekile ekunciphiseni ukuvuvukala kungathuthukisa imiphumela yomzimba.
Ukubona ukuvuvukala njengenhloso entsha yokwelashwa kokuvimbela ngokuqinisekile kuyisizathu sokulindela, futhi singalindela ukucwaninga okukhulu okwamanje okuzogxila kulolo lwazi. Kodwa-ke, kufanele futhi sibe nokungabaza ukuthi isidakamizwa esithile esetshenziselwa ukuhlolwa kwe-CANTOS-canakinumab-siyoke sibe yindlela yokwelapha ebalulekile kubantu abasengozini ye-cardiovascular.
Ukuvuvukala ne-Atherosclerosis
Kuye kwaziwa amashumi eminyaka ukuthi ukuvuvukala kudlala indima ekutheni i- atherosclerosis , futhi ikakhulukazi, amangqamuzana avuthayo ayingxenye evelele yama-atherosclerotic plaques. Phakathi kwalawo macwecwe, ama-macrophages (uhlobo lwama-white cell cell) asethathe ukukhipha i- LDL cholesterol ukukhipha izinto eziningi ezivuthayo, okubangela ukuvuvukala. Kukholelwa iminyaka eminingi ukuthi lokhu ukuvuvukala kusiza ekuholeni ukukhula kwamapletiki ngisho nokuqhekeka kwepletiki. Ukuphuka kwesikhala kungabulala. Ukuphuka kwama-plaque ngokuvamile kuyisenzakalo esenza ukuthi ekugcineni kuvezwe isifo se-coronary acute , okuholela e- angina engaqiniseki noma ekuhlaselweni kwenhliziyo .
Kukhona nobufakazi obuvela ezivivinyweni zomtholampilo ezibonisa ngokuqinile ukuvuvukala kubalulekile ekunqumeni umphumela womuntu nge-atherosclerosis. Ngokuyinhloko, amazinga egazi aphezulu amamaki amabili okuvuvukala- amaprotheni asebenzayo eC (i-CRP) kanye ne-interleukin-6-ahlobene nengozi eyengeziwe yokuhlaselwa kwenhliziyo, nezinye izenzakalo zenhliziyo.
Ngaphezu kwalokho, ucwaningo luye lwabonisa ukuthi izidakamizwa ze-statin- ezidume ngokunciphisa amazinga e-cholesterol, kodwa okunciphisa ukuvuvukala-ziphumelela ekuthuthukiseni imiphumela yomtholampilo yabantu abanobungozi obuphezulu abanamazinga aphezulu e-CRP, ngisho nalapho amazinga abo e-cholesterol engakhulumi kakhulu. (Ochwepheshe abaningi bakholelwa ukuthi kungenxa yokuthi ama-statins enza okungaphezu nje kokuthi "ukunciphisa" i-cholesterol eyenza ukuthi iphumelele ngokukhethekile ekunciphiseni ubungozi benhliziyo. Funda ngalokho okwenza ama-statin "ahluke." )
Kodwa-ke, kuze kufike isilingo se-CANTOS, akukho ukuhlolwa komtholampilo okwake kwabonisa ukuthi ukunciphisa ukuvuvukala kwamagciwane, ngaphandle kokunciphisa amazinga e-cholesterol, kuzokwenza ngcono imiphumela yomtholampilo.
I-CANTOS Trial
Isivivinyo se-CANTOS sasebenzisa umuthi oyingqayizivele ohlose ingxenye ethile yempendulo yokuvuvukala. I-Canakinumab yi-antibody yamonoclonal evimbela i-interleukin-1b, i- cytokine ebaluleke kakhulu endleleni yokuvuvukala ehlobene ne-interleukin-6. I-Canakinumab ivunyelwe iminyaka eminingana yokwelashwa kwezifo ezinzima ze-rheumatologic, kodwa ayingakaze isetshenziselwe ukuphatha isifo senhliziyo.
Esivivinyweni se-CANTOS, abantu abangaphezu kuka-10 000 abasinde ekuhlaselweni kwenhliziyo, nokuthi ngubani ophakamise amazinga egazi le-CRP, bekungakahleleki ukuthola ama-injection ye-canakinumab noma i-placebo.
Ngemuva kokulinganiselwa kweminyaka engu-3.7 yokulandelwa, abantu abangahle baluthole ukuthola izilonda eziyi-150 mg we-canakinumab (kodwa hhayi labo abanama-50 mg noma 300 mg) banciphise ingozi yemicimbi ye-cardiovascular (njengoba kulinganiswa ngophawu lokugcina ehlanganisa ukuhlasela kwenhliziyo okungenabulawa, isifo esingenabulala, noma ukufa komzimba). Ukufa okuphelele akuzange kuthinteke yi-canakinumab.
Inzuzo ezuzwe ngama-injection angu-150 mg, ngenkathi ibonakala ngokuphawulekayo, yayinobukhulu obuncane, futhi kubaluleke kakhulu emtholampilo. Esikhathini seqembu le-placebo, kwakukhona izenzakalo zemitholampilo ezingu-4.11 ngeminyaka engu-100 yomuntu, vs 3.86 imicimbi engama-100 umuntu-iminyaka kubantu abathola 150 mg canakinumab.
Ngamanye amazwi, ukunciphisa ngokuphelele engozini ebantwini besifundo kwakungaphansi kwamaphesenti angu-1 ngemuva kweminyaka emine yokwelapha. Ngenkathi le nsizakalo ingasihle kakhulu, yayisabonakaliswa ngokuphawulekayo. Ngakho-ke, imiphumela yesilingo se-CANTOS ibonisa ngokucacile, okokuqala, ukuthi ukwelapha okulwa nokuvuvukala kungathuthukisa imiphumela jikelele yezinhliziyo ezinabantu abasengozini enkulu.
Kubalulekile ukucindezela ukuthi i-canakinumab akuyona imithi yokulwa nokuvuvukala. Esikhundleni salokho, kuhloswe ngesici esithile nesingqayizivele sokwehla okuvuthayo. Akucaci ukuthi izidakamizwa ezithinta ezinye izici zokuvuvukala nazo zizozuzisa. Eqinisweni, kwaziwa kahle ukuthi izidakamizwa ezingekho-steroidal ezivuvukala (i-NSAIDS) zibonakala ziba yingozi engozini yomzimba. Ngakho-ke, inzuzo ebonakalayo yenhliziyo ebonwe nge-canakinumab ayisebenzi kwezinye izidakamizwa ezilwa nokuvuvukala.
Njengombhalo ohlangothini, abantu abaseceleni kweCANTOS abathola i-canakinumab babonwa ukuthi banomngcipheko wokunciphisa ukufa komdlavuza wamaphaphu -nye isimo lapho ukuvuvukala kucatshangwa ukuthi kudlala indima evelele. Ngakho isilingo se-CANTOS siphinde savula indlela entsha yokucwaninga ngokuvuvukala nomdlavuza.
Isenzakalo esibi esibucayi esibonakala nge-canakinumab esilingo se-CANTOS kwaba ukwanda okuncane kodwa okuphawulekayo kokufa ngenxa yezifo. Njengoba impendulo enamandla yokuvuvukala ivame ukudingeka ekuvimbeleni izifo, lokhu ukuthola akuzange kusimangaze okukhulu.
Konke lokhu kusho
Akungabazeki ukuthi ukuhlolwa kwe-CANTOS kuzoholela ekusetshenzisweni okubanzi kwe-canakinumab yokunciphisa izenzakalo zenhliziyo kubantu abasengozini enkulu. Akukhona nje ukuthi inzuzo yomtholampilo yangempela evela ku-canakinumab ibukeka kahle, kodwa futhi le mithi ibiza kakhulu. Ukwelashwa kwamanje nge-canakinumab, kubantu abanezimo ezinzima ze-rheumatologic, kubiza cishe u-$ 200,000 ngonyaka. Izinga eliphansi kakhulu lezinzuzo zenhliziyo elibonwe esilingo seCANTOS cishe ngeke livumele ukusetshenziswa kwezidakamizwa ezibizayo.
Ngakho-ke, cishe, ukubaluleka kokucwaninga kwe-CANTOS akukona ukuthi kuye kwaveza ukwelashwa okusha okuvimbela isifo senhliziyo, kodwa kunalokho, ukuthi kuboniswe isisombululo esisha sokucwaninga.
Kuze kube manje, ukunciphisa ingozi yemithwalo yemithwalo ngemithi kuye kwanciphisa kakhulu ukuchithwa kwe-cholesterol (ngokuyinhloko nama-statins), futhi mhlawumbe ukuvimbela ukucindezeleka (nge- aspirin ). Manje ibonakala, ngokucacile nakakhulu kunanini ngaphambili, ukuthi ukucindezela izici eziqondile zokuphendula okuvuthayo emithanjeni yegazi kunganciphisa nesigameko sezinhlekelele zenhliziyo.
Singalindela izinkampani ezenza imithi ukuba zisebenzise ngokushesha le ndlela yokwelapha entsha, futhi zithuthukise kakhulu ukuthuthukiswa kwazo kwamanye ama agent anganciphisa ukuvuvukala kwamasongo. Uma lo mzamo uphuma konke okufana nalokho ochwepheshe abaningi ababikezelayo manje, isivivinyo se-CANTOS empeleni kuzobhekwa njengento eyinhloko ekwelapheni isifo senhliziyo-noma ngabe ukusetshenziswa kwe-canakinumab ngokwayo kuba yindawo evamile.
Izwi elivela
Manje kubonakala ngokuqinisekile ukuthi ukuvuvukala kudlala indima enkulu ekuthuthukiseni isifo sokuqina kwesifo somzimba, futhi emiphumeleni yabantu abane-atherosclerotic vascular disease. Isivivinyo se-CANTOS sibonise ukuthi ukwelashwa okuhlosiwe okuhloswe kuzo izici ezithile zempendulo evuthayo kungathuthukisa kakhulu umphumela wabantu abasengozini enkulu.
Ngenkathi i-canakinumab-isidakamizwa esetshenziselwa ukuhlolwa kwe-CANTOS-angeke isakaze isetshenziselwe ukusetshenziswa kwezifo zenhliziyo, abacwaningi manje sebeyakhe indlela entsha yokwelapha lesi sifo. Eminyakeni ezayo singalindela ukuzwa okuningi mayelana nokuvuvukala njengesisusa se-atherosclerosis, futhi mayelana nemithi emisha ehlose ukuvimbela lokhu kuvutha.
> Imithombo:
> Libby P, Ridker PM, uHansson GK, i-Leducq Transatlantic Network ku-Atherothrombosis. Ukuvuvukala ku-Atherosclerosis: Kusuka ku-Pathophysiology ukuze Usebenze. J Am Coll Cardiol 2009; 54: 2129.
> Ridker PM, u-Everett BM, u-Thuren T, et al. Ukwelashwa Okungenakuvuthayo Nge-Canakinumab ye-Atherosclerotic Disease. N Engl J Med 2017; I-DOI: 10.1056 / NEJMoa1707914.
> Weber C, Noels H. Ukwelashwa Kwegazi: I-Pathogenesis Yamanje Nezinketho Zezokwelapha. Nat Med 2011; 17: 1410.