Muzhizha ra2017, vanotsvakurudza vanorondedzera nezvezviitiko zvekuedzwa kweCANTOS, umo kurapwa nemishonga inopesana nemaperembudzi canakinumab (Illaris, Novartis) yakaderedza zvakanyanya ngozi yezviitiko zvikuru zvepfungwa mukati mevanhu vakanga vari pangozi.
Nyanzvi dzakawanda dzinofunga kuti CANTOS ichayeukwa semuedzo unokosha, sezvo ihwo huno huchapupu hwekutanga hwechokwadi hwechirwere chekuti mushonga wezvinodhaka zvakananga kuedza kuderedza kupisa kunogona kuvandudza migumisiro yemoya.
Kuziva kurwiswa sechinhu chitsva chekurapa kunodzivirira zvechokwadi chikonzero chekutarisira, uye tinogona kutarisira kuwanda kwekutsvakurudza iye zvino kuti kuve kwakananga mune izvozvi. Zvisinei, isu tinofanirawo kunge tisina chokwadi kuti mishonga inoshandiswa mumutambo weCANTOS-canakinumab-ichazombova yakakosha kurapa kwevanhu vari pamatambudziko epfungwa.
Kuvhiringidza uye Atherosclerosis
Izvo zvave zvichizivikanwa kwemazana emakore kuti kuputira kunobatsira pane atherosclerosis , uye kunyanya, masero aya anopisa anonyanya kukosha kwe atherosclerotic plaques. Mukati mawo makanda, macrophage (rudzi rwechichena chemuviri weropa) iyo yatora oxidized LDL cholesterol kusununguka pane zvakawanda zvekuvhiringidza zvinhu, zvichikonzera kuputika. Ive yakatendwa kwemakore kuti kupisa uku kunobatsira kutungamirira kukura kwemavara uye kunyange kuputika kwemavara. Kuputika kwemukati kunogona kuuraya. Kuparara kwepara inowanzova chiitiko chinoguma chichikonzera chirwere chinonzi coronary syndrome , zvichiita kuti angina isina kugadzikana kana chirwere chemwoyo .
Pane humwe uchapupu hunobva kuchipatara miedzo inonyatsoratidza kuti kupisa kunokosha mukugadzirisa mhinduro yemunhu ne atherosclerosis. Kunyanya, kukwidziridzwa kweropa kwemavara maviri ekuvhiringidza -C-reactive protein (CRP) uye interleukin-6-inobatanidza nehuwandu hwekukuvara kwemoyo, uye zvimwe zviitiko zvepfungwa.
Uyezve, zvidzidzo zvakaratidza kuti chimiro chemishonga -iyo inozivikanwa nekuderedza cholesterol, asi iyo inoderedza kupisa-inobudirira mukuvandudza migumisiro yekliniki yevanhu vane ngozi yakawanda vane mazinga akakura eRPP, kunyange kana cholesterol yavo isinganyanyi kukwirira. (Nyanzvi dzakawanda dzinofunga kuti ndeyekuti mitemo inowedzera zvinopfuura "kungoita" kuderedza cholesterol inoita kuti iite zvakakwana mukuderedza mungozi yemwoyo.) Verenga pamusoro pezvinoita kuti mitemo "yakasiyana." )
Zvisinei, kusvikira chirongwa cheCANTOS, hapana kliniki yekudzidza yakanga yakamboratidza kuti kuderedza kuputika kwemavhutuko, pasina kuderedza chelesterol mazinga, zvingagadzirisa zvibereko zvechipatara.
The CANTOS Trial
Chirwere cheCANTOS chakashandisa mukana wakasiyana-siyana wezvinodhaka unofungidzira chimwe chinhu chekuvhiringidza kupindura. Canakinumab inonzi monoclonal antibody inhibits interleukin-1b, cytokine iyo inonyanya kukosha mumugwagwa unovhiringidza une chokuita ne interleukin-6. Canakinumab yakagamuchirwa kwemakore anoverengeka kuitira kurapwa kweimwe dambudziko rerheumatologic, asi yakanga isina kumboshandiswa kurapa chirwere chemwoyo.
Muchiedzo cheCANTOS, vanhu vanopfuura 10 000 vakanga vapona marwadzo emwoyo, uye avo vainge vakwidziridza mapuropa eRPP, vakashandurwa kuti vawane majekiseni e-canakinumab kana placebo.
Mushure mekuvhara kwemakore 3.7 ekutevera, vanhu vainge vakagadziriswa kugamuchira 150 mg injection ye canakinumab (asi kwete avo vakagamuchira 50 mg kana 300 mg) vakawandisa kuderedza mungozi yezviitiko zvepfungwa (sezvinoenzaniswa nemagumo ekupedzisira iyo inosanganisira kwete-inouraya mwoyo yekurwisa, chirwere chisina kuuraya, kana kufa kwemwoyo. Kufa kwepasi rose kwakanga kusina kukanganiswa ne canakinumab.
Kubatsirwa kwakagadziridzwa nemishonga 150 mg, iyo inoratidzika, inokosha, uye yekukosha kwekliniki yakakosha. Muboka re-placebo, pakanga pane zviitiko zvekliniki 4.11 zvevanhu 100-makore, vs 3.86 zviitiko zvevanhu 100-makore muvanhu vanogamuchira 150 mg canakinumab.
Mune mamwe mazwi, kurerutsa zvachose muhutachiwana muhuwandu hwekudzidza kwaive pasi pe1 muzana mushure memakore mana ekurapa. Kunyange zvazvo ichi chiyero chekubatsira hachisi chakanakidza, chakanga chichinyanya kukosha. Nokudaro, migumisiro yechirango cheCANTOS inoratidza zvakajeka, kwekutanga, kuti kurapa kunopesana nekuputira kunogona kuvandudza zvizere zvepfungwa dzemumwoyo kune vanhu vane ngozi yakawanda.
Zvakakosha kudzvinyirira zvekare kuti canakinumab haisi mhanho-ye-the-mill anti-inflammatory drug. Pane kudaro, inotarirwa pane imwechete uye yakasiyana-siyana yezvokuvhiringidza kuputika. Hazvisi pachena kuti zvinodhaka zvinokanganisa zvimwe zvekuvhiringidza zvingabatsira zvakare. Zvechokwadi, zvinonyatsozivikanwa kuti asiri-steroidal anti-inflammatory drugs (NSAIDS) inoita kuti iwedzere kuipa kwehutano hwemwoyo. Saka, iyo inoratidzika yemwoyo inobatsira inowanikwa ne canakinumab haina kushandiswa kune dzimwe zvinorwisa zvinodhaka zvinodhaka.
Sevhesi yechipfuva, vanhu vari mumuedzo weCANTOS avo vakagamuchira canakinumab vakacherechedza kuti vane mikana yakaderera yekufa kubva pamukenza wepapupa -imwe mamiriro ayo apo kuvhiringidzika kunofungidzirwa kutamba basa rakakosha. Saka chirongwa cheCANTOS chakavhurawo nzira itsva yekutsvakurudza nezvekuputika nekenza.
Chiitiko chikuru chakaipa chakaonekwa ne canakinumab mumuedzo weCANTOS chaive chidiki asi chiwandu chinokosha pakufa nekuda kwezvirwere. Sezvo kupindura kwakasimba kwekuvhiringidza kunowanzodiwa pakurwisana nehutachiona, kuwanikwa uku kwakanga kusiri kushamisa kukuru.
Zvose Izvi Zvinoreva
Hazvina chokwadi kuti chirwere cheCANTOS chichatungamirira kushandiswa kwakawanda kwe canakinumab nekuderedza zviitiko zvepfungwa kuvanhu vari pangozi. Hazvirevi chete kuti chipatara chaiyo inobatsirwa kubva ku canakinumab inoratidzika zvakanaka, asiwo ichi chinodhaka chinodhura zvikuru. Kurapa ikozvino ne canakinumab, kune vanhu vane rheumatologic zvakanyanya, zvinodhura madhora 200 000 pagore. Kuwedzerwa kwemuviri wepfungwa inobatsira mukati mekutongwa kwaCANTOS hakuzombotenderwi kushandiswa kwezvinodhaka zvakadai.
Saka, zvichida, kukosha kwekudzidza kweCANTOS hakusi kuti yakagadzirisa mushonga chaiwo wekudzivirira chirwere chemwoyo, asi, kuti yakagadzirisa chinangwa chitsva chekutsvakurudza.
Kusvikira ikozvino, kuderedza moyo wehutano nemishonga kwave kusinganyanyi kuderedza cholesterol kuderedza (kunyanya nemasimoni), uye zvichida kudzivisa hutachiona (ne aspirin ). Iko zvino inowanikwa, zvakajeka zvikuru kupfuura kare kare, kuti kudzvinyirira zvimwe zvikamu zvekuvhiringidza kupindura mukati memidziyo yeropa kunogonawo kuderedza kuitika kwematambudziko emwoyo.
Tinogona kutarisira makambani emishonga kuti vashandise kushandisa nzira iyi itsva yekurapa, uye kunyanya kuwedzera kukura kwavo kwevamwe vashandi vanogona kuderedza kuvhiringidzika kwemavhukira. Kana kuedza uku kuchibvisa chero chinhu chakafanana nezvakawanda zvezvinozivikanwa zvino, nyanzvi yeCANTOS inozopedzisira yaonekwa sechinhu chakakosha mukurapa kwehutano hwepfungwa-kana kuti kushandiswa kwe canakinumab pachako kunowanzova yakawanda nzvimbo.
Shoko Rinobva
Iko zvino inowanikwa zvinyatsove pachena kuti kuvhunika kunobatanidzwa mubato guru mukusimudzirwa kweherosclerosis, uye mumagumisiro evanhu vane atherosclerotic vascular disease. Chirwere cheCANTOS chakaratidza kuti chirongwa chinotarisirwa chinangwa pane zvimwe zvikamu zvekuvhiringidza kupindura kunogona kuchinja zvakanyanya mugumisiro wevanhu vari pangozi yakanyanya.
Kunyange zvazvo canakinumab-chirwere chinoshandiswa mumuedzo weCANTOS-chisingambofi chakapararira kushandiswa kwehutano hwehutano, vatsvakurudzi ikozvino vakaisa nzira itsva yekurapa chirwere ichi. Mumakore anotevera tinogona kutarisira kunzwa zvakawanda pamusoro pekuputika sechikonzero chekushaya atherosclerosis, uye nezvemishonga mitsva inotarisirwa kubvisa kupopota uku.
> Sources:
> Libby P, Ridker PM, Hansson GK, Leducq Transatlantic Network pamusoro peAtherothrombosis. Kuvhiringidza muAtherosclerosis: Kubva Pathophysiology Kuti Uite. J Am Coll Cardiol 2009; 54: 2129.
> Ridker PM, Everett BM, Thuren T, et al. Anti-inflammatory Therapy Ne Canakinumab yeAtherosclerotic Disease. N Engl J Med 2017; DOI: 10.1056 / NEJMoa1707914.
> Weber C, Noels H. Atherosclerosis: Current Pathogenesis uye Zvokurapa Zvimwe. Nat Med 2011; 17: 1410.