M'chaka cha 2017, ofufuza anafotokoza zotsatira za mayesero a CANTOS, omwe mankhwala omwe amatsutsana ndi zotupa mankhwala a canakinumab (Illaris, Novartis) adachepetsa kwambiri ngozi ya zochitika zazikulu za mtima mwa anthu omwe anali pangozi yaikulu.
Akatswiri ambiri amakhulupirira kuti CANTOS idzakumbukiridwa ngati mayesero ofunika kwambiri, chifukwa ndiyi yoyamba yotsimikiziridwa kuti mankhwala omwe amathandiza kuchepetsa kutupa angathe kusintha zotsatira za mtima.
Kudziwa kutupa ngati chithunzithunzi chatsopano cha chithandizo choteteza ndizo chifukwa chokhalira ndi chiyembekezo, ndipo tikuyembekezerapo kafukufuku wochuluka tsopano kuti ayambe kutsogolo. Komabe, tiyeneranso kukayikira kuti mankhwala omwe akugwiritsidwa ntchito ku CANTOS-canakinumab-adzasanduka chithandizo chofunikira kwa anthu omwe ali pamwambamo wamtima.
Kutupa ndi Atherosclerosis
Zakhala zikudziwika kwa zaka makumi ambiri kuti kutupa kumathandiza kuti matenda a atherosclerosis ayambe kugwira ntchito, ndipo makamaka, maselo otupa ndi ofunika kwambiri pa miyala ya atherosclerotic. M'malo mwake, macrophages (mtundu wa maselo oyera a magazi) omwe atenga zakumwa zotchedwa LDL cholesterol kutulutsa zinthu zambiri zotupa, zomwe zimayambitsa kutupa. Zakhala zikukhulupiriridwa kwa zaka zambiri kuti kutukuka kumathandiza kutsogolera kukula kwa ziphuphu komanso kupasuka kwala. Kutuluka kwa chipika kungakhale chakupha. Kuphulika kwapadera nthawi zambiri kumakhala kovuta kumayambitsa matenda aakulu , omwe amachititsa kuti angina osakhazikika kapena matenda a mtima .
Palinso umboni wochokera ku mayesero a kachipatala omwe amasonyeza kuti kutupa n'kofunika pozindikira zotsatira za munthu ndi matenda a atherosclerosis. Makamaka, kuchuluka kwa magazi m'magazi awiri a kutupa -Puloteni yogwira ntchito (C-reactive protein) (CRP) ndi interleukin-6-zimakhala ndi chiopsezo chowonjezeka cha mtima, ndi zochitika zina zamtima.
Kuwonjezera pamenepo, kafukufuku wasonyeza kuti mankhwala osokoneza bongo, omwe amadziwika kuti amachepetsa kupweteka kwa mafuta m'thupi, komanso amachepetsanso kutupa-amatha kusintha zotsatira zachipatala za anthu omwe ali ndi chiopsezo chachikulu omwe ali ndi miyezo yapamwamba ya CRP, ngakhale kuti cholesterol chawo sichikwera kwambiri. (Akatswiri ambiri amakhulupirira kuti chifukwa chakuti mafano amangochita zambiri kuposa "kuchepetsa" cholesterol chomwe chimapangitsa kuti apindule kwambiri pa kuchepetsa matenda a mtima. Werengani za zomwe zimapangitsa ma statins "osiyana." )
Komabe, mpaka chiyeso cha CANTOS, palibe phunziro lachipatala lomwe lawonetsa kuti kuchepetsa kutupa kwa mitsempha, popanda kuchepetsa kuchepa kwa cholesterol, kungapangitse zotsatira zachipatala.
Chiyeso cha CANTOS
Mayesero a CANTOS adagwiritsa ntchito mankhwala osokoneza bongo omwe amawunikira mbali yeniyeni ya kuyankha kotupa. Canakinumab ndi anti-monoclonal antibody yomwe imaletsa interleukin-1b, cytokine yomwe imakhala yofunika kwambiri mu njira yotupa yokhudza interleukin-6. Canakinumab yavomerezedwa kwa zaka zingapo kuti adziwe matenda oopsa a rheumatologic, koma sanagwiritsidwepo ntchito pochiza matenda a mtima.
Mu kuyesedwa kwa CANTOS, anthu opitirira 10,000 omwe adapulumuka ku matenda a mtima, ndipo amene adakweza kuchuluka kwa magazi a CRP, adapangidwanso kuti alandire jekeseni wa canakinumab kapena placebo.
Pambuyo pa zaka 3.7 zotsatila, anthu omwe sanalandire mavitamini 150 mg a canakinumab (koma osati omwe ali ndi 50 mg kapena 300 mg) adachepetsa chiopsezo cha zochitika za mtima (monga momwe zimakhalira ndi mapeto a gulu kuphatikizapo matenda osokoneza mtima, kupweteka kosapweteka, kapena kufa kwa mtima). Kufa kwathunthu sikudakhudzidwe ndi canakinumab.
Zopindulitsa zomwe zinaperekedwa ndi injini ya 150 mg, pamene ziwerengero zowonjezera, zinali zazing'ono kwambiri, komanso zazing'ono zamakono. Mu gulu la placebo, panali zochitika zachipatala 4.11 pazaka 100 za munthu, vs 3.86 zochitika pa zaka 100 za anthu omwe amalandira 150 mg canakinumab.
Mwa kuyankhula kwina, kuchepetsa kwenikweni mowopsya mu chiwerengero cha ophunzira kunali osachepera 1 peresenti pambuyo pa zaka zinayi za chithandizo. Ngakhale kuti phindu limeneli silili lochititsa chidwi, linali lofunika kwambiri. Motero, zotsatira za mayesero a CANTOS zimasonyeza bwino, kwa nthawi yoyamba, kuti mankhwala odana ndi kutupa amatha kusintha zotsatira za mtima wa anthu omwe ali ndi chiopsezo chachikulu.
Ndikoyenera kupanikizanso kachiwiri kuti canakinumab si mankhwala osokoneza bongo. Mmalo mwake, iwo akuwonekera pa gawo lapadera ndi lapadera la kutupa kotupa. Sizowonekeratu kuti mankhwala omwe amakhudza mbali zina za kutupa angakhale opindulitsa. Ndipotu, zimadziwika bwino kuti mankhwala osagwiritsidwa ntchito poletsa kutupa (NSAIDS) amawoneka oopsa kwambiri. Choncho, kupindula kwa mtima komwe kumapezeka ndi canakinumab sikugwiranso ntchito ndi mankhwala ena odana ndi kutupa.
Monga ndemanga, mbali ya mayesero a CANTOS omwe analandira canakinumab anawonedwa kuti ali ndi chiopsezo chochepa cha imfa kuchokera ku khansa ya m'mapapo - mkhalidwe wina momwe kutukudzidwa kumalingalira kuti kumakhala ndi udindo wapadera. Choncho mayesero a CANTOS atsegulira njira yatsopano yofufuza za kutupa ndi khansa.
Chochitika chachikulu chomwe chinawonetsedwa ndi canakinumab mu kuyesedwa kwa CANTOS chinali kuwonjezeka kwapang'ono koma kodabwitsa kwa imfa chifukwa cha matenda. Popeza kuyankha kwakukulu kotupa kumakhala kofunikira pomenyana ndi matenda, izi sizinali zodabwitsa.
Zomwe Zonsezi Zikutanthauza
N'zosakayikitsa kuti mayeso a CANTOS amachititsa kuti anthu ambiri azigwiritsa ntchito mankhwalawa kuti athe kuchepetsa mavuto a mtima kwa anthu omwe ali pangozi yaikulu. Sikuti kliniki yeniyeni imapindula ndi canakinumab yokongola kwambiri, komanso mankhwalawa ndi okwera mtengo kwambiri. Chithandizo chamakono ndi canakinumab, mwa anthu omwe ali ndi vuto lalikulu, zimayendetsa madola 200,000 pachaka. Mapulogalamu apakati a mtima omwe amapezeka mu mayeso a CANTOS sangavomereze kugwiritsa ntchito mankhwala okwera mtengo ngati amenewa.
Kotero, mwachiwonekere, tanthauzo la kufufuza kwa CANTOS sikuti lapeza njira yatsopano yothandizira matenda a mtima, koma, kuti yatsimikizira cholinga chatsopano cha kafufuzidwe.
Mpaka lero, kuchepetsa kuopsa kwa mtima ndi mankhwala sikungatheke kuchepetsa kupatsirana kwa kolesterolini (makamaka ndi statins), ndipo mwina kuteteza thrombosis (ndi aspirin ). Tsopano zikuwonekera, momveka bwino kuposa kale lonse, kuti kulepheretsa mbali zina za kupweteka kumayendedwe m'mitsempha ya mitsempha kungathandizenso kuchepa kwa mitsempha ya mtima.
Titha kuyembekezera kuti makampani azachipatala azigwiritsa ntchito njira yatsopanoyi popititsira patsogolo mankhwalawa, ndipo akuwongolera kwambiri chitukuko cha ena othandizira kuti athe kuchepetsa kupweteka kwakukulu. Ngati khamali likutulutsa chilichonse monga momwe akatswiri ambiri amaneneratu, yesero la CANTOS lidzatengedwa kuti ndilopambana kwambiri pakuchiza matenda a mtima - kaya ntchito ya canakinumab yokha ingakhale yofala.
Mawu Ochokera
Tsopano zikuwoneka zowona kuti kutupa kumathandiza kwambiri pakukula kwa matenda a atherosclerosis, ndi zotsatira za anthu omwe ali ndi atherosclerotic vascular disease. Chiyeso cha CANTOS chawonetsa kuti chithandizo chowongolera chomwe chimayang'aniridwa pazinthu zina za kutukumula kumatha kusintha kwambiri zotsatira za anthu omwe ali pachiopsezo chachikulu.
Ngakhale canakinumab-mankhwala omwe amagwiritsidwa ntchito pa mayeso a CANTOS-sangagwiritsidwe ntchito mofala kwa matenda a mtima, ofufuza tsopano ayambitsa njira yatsopano yochizira matendawa. M'zaka zikubwera tikhoza kuyembekezera kumva zambiri zokhudza kutupa ngati chifukwa cha matenda a atherosclerosis, komanso za mankhwala atsopano omwe cholinga chake ndi kuchepetsa kutupa uku.
> Zotsatira:
> Libby P, Ridker PM, Hansson GK, Leducq Transatlantic Network pa Atherothrombosis. Kutupa mu Matenda Atherosclerosis: Kuchokera Pathophysiology Kuti Uchite. J Am Coll Cardiol 2009; 54: 2129.
> Ridker PM, Everett BM, Thuren T, et al. Thandizo loletsa kutupa ndi Canakinumab kwa Matenda Atherosclerotic. N Engl J Med 2017; DOI: 10.1056 / NEJMoa1707914.
> Weber C, Noels H. Matenda Atherosclerosis: Masiku Ano Pathogenesis ndi Njira Zothandizira. Nat Med 2011; 17: 1410.