Xilliga xagaaga 2017, baarayaashu waxay ka soo warbixiyeen natiijooyinka ka soo baxa CANTOS ee tijaabada, kaas oo lagu daaweyn karo daawada canakinumab (Illaris, Novartis) si weyn u yareeyey khatarta ugu weyn ee dhacdooyinka wadnaha iyo xididada dadka khatarta sare leh.
Khubarada intooda badani waxay aaminsan yihiin in CANTOS la xasuusnaado inay tahay maxkamad taariikhi ah, maaddaama ay ka dhigtay caddaynta ugu horeysa ee daaweyneed ee daaweynta daroogada si gaar ah loogu talagalay dhimista infekshinka waxay hagaajin kartaa natiijada wadnaha.
Aqoonsiga bararinta bartilmaameed cusub oo loogu talagalay daaweynta ka hortagga ah ayaa dhab ahaan ah sabab u ah rajo-gelinta, waxaana ka filan karnaa tiro badan oo cilmi-baaris ah si loo eego dhinacaas. Si kastaba ha noqotee, waa in aan ka shakisanahay in daroogada gaarka ah ee loo adeegsado CANTOS tijaabada-canakinumab-marwalba noqon doono door muhiim ah daaweynta dadka ku jira khatarta wadnaha.
Caabuqa iyo Atherosclerosis
Waxaa la ogaaday tobannaan sano in caabuqu uu door ka ciyaaro atherosclerosis , gaar ahaanna, unugyada bararka leh ayaa ah mujtamaca caanka ah ee dabaqyada atherosclerotic. Xirdhooyinkaas, makrophages (nooca unugyada dhiigga cad) ee qaaday maaddada " LDL" kolesteroolka ayaa sii deynaya marti-geliyeyaasha walxaha bararsan, kicin kara barar. Waxaa la rumaysan yahay in sanado badan oo cudurkani uu ka caawiyo inuu horseedo korriin iyo xitaa dillaac. Dillaaca lakabka ayaa keeni kara dhimasho. Dillaaca lakabka badanaa waa dhacdada ugu dambeysa ee keenta cilladda cudurka cilladeysan , oo keena angina aan xasilloonayn ama wadne xanuun .
Waxaa sidoo kale jira caddayn tijaabo ah oo ku saabsan tijaabooyinka caafimaad ee si adag u soo jeedinaya in caabuqu uu muhiim u yahay go'aaminta natiijada qofka ee atherosclerosis. Gaar ahaan, heerarka dhiigga ee sareeya ee laba calaamadood oo caabuq ah - borotiinka C-reactive (CRP) iyo interleukin-6-wuxuu la xiriiraa khatarta sii kordheysa ee wadna xanuunka, iyo dhacdooyinka kale ee wadnaha.
Intaa waxaa dheer, daraasaduhu waxay muujiyeen in daroogooyinka dawada -waxay caan u yihiin hoos u dhigidda heerarka kolestaroolka, laakiin taasi waxay sidoo kale hoos u dhigtaa caabuq- waxay ku habboontahay hagaajinta natiijooyinka kiliiniga ee shakhsiyaadka khatarta sare leh ee leh heerarka CRP-ga, xitaa marka heerarka kolestaroolka aysan gaarin heer sare. (Khubaro badani waxay aaminsan yihiin in ay tahay sababtoo ah "statins" wax badan oo ka badan "kaliya" hoos u dhigidda kolestaroolka taasoo ka dhigaysa mid si wax ku ool ah u yareynaya khatarta wadnaha iyo xididdada.
Si kastaba ha noqotee, ilaa inta laga gaarayo CANTOS, daraasad cilmi-baaris ah weligeed muu muujin in yareynayo bararka xanuunka, iyada oo aan la yareeynin heerarka kolestaroolka, ayaa hagaajin doona natiijooyinka bukaan-socodka.
CANTOS Trial
Dacwada CANTOS waxay ka faa'iideysatay daroogo gaar ah oo bartilmaameed u ah qayb ka mid ah jawaab celinta. Canakinumab waa unug monoklonal ah oo difaacaya interleukin-1b, cytokine oo muhiim u ah jidka bararsan ee la xiriira interleukin-6. Canakinumab ayaa loo ogolaaday dhowr sano daaweynta cudurada rheumatoloji-ga qaarkood, laakiin marna looma isticmaalin daaweynta cudurka wadnaha.
Maxkamadaynta CANTOS, in ka badan 10,000 oo qof oo ka badbaaday weerarrada wadnaha, iyo kuwa kor u qaaday heerarka dhiigga ee CRP, ayaa loo kala saaray si loo helo irbadaha kanakinumab ama placebo.
Ka dib celcelis ahaan 3.7 sano oo dabagal ah, dadka loo kala soocay in la siiyo 150 mg koobi ah canakinumab (laakiin kuwa aan helin 50 mg ama 300 mg) waxay leeyihiin halis ahaan tirooyinka dhacdooyinka wadnaha (sida lagu qiyaaso dhamaadka dhamaadka oo ka kooban wadno-dil aan wadnaha ahayn, madax-dhiigfuranka aan caadiga ahayn, ama dhimashada wadnaha. Dhimashada guud ee saamaynta kuma yeelaneyso canakinumab.
Faa'idada lagu gaarey 150 mg oo cirbadeyn ah, iyada oo xisaab ahaan aad u muhiim ah, waxay ahayd mid aad u yar, iyo muhiimada bukaan-jiifka. Kooxdu waxay ku jirtaa 4.11 dhacdooyin caafimaad oo ah 100 qof oo sannadkii, 3.86 dhacdooyinka 100 qof oo sanadba ah dadka qaata 150 mg canakinumab.
Si kale haddii loo dhigo, hoos udhaca khatarta ah ee dadka daraasaddu waxay ahayd wax ka yar boqolkiiba 1 kaddib markii lagu qiyaasay afar sano oo daaweyn ah. Inkastoo heerkani aanu ahayn mid aad u cajaa'ib leh, hadana weli waa mid muhiim ah. Sidaas daraadeed, natiijooyinka CANTOS ayaa si cad u muujineysa, markii ugu horeysay, daaweyntan ka hortagga dabiiciga ah waxay hagaajin kartaa natiijooyinka wadnaha iyo wadnaha ee khatarta sare leh.
Waxaa haboon in mar kale la adkeeyo in canakinumab aysan ahayn daroogo udubdhexaad ah anti-bararka. Taa baddalkeeda, waxa lagu beegsanayaa qayb gaar ah oo gaar ah oo ka mid ah cascade. Maaha wax cad in daawooyinka saameeya dhinacyada kale ee caabuqa ay sidoo kale faa'iido u yeelanayaan. Xaqiiqdii, waxaa si wacan loo og yahay in daawooyinka aan dawooyinka ahayn ee anti-inflammatory (NSAIDS) ay u muuqdaan kuwo ka sii daraya khatarta wadnaha. Sidaa daraadeed, faa'idada daawada wadnaha ee muuqata ee canakinumab laguma daboolayo daawooyinka kale ee ka hortagga bararka.
Dhinaca kale, dadka ku jira CANTOS ee tijaabada ah ee qaada canakinumab ayaa loo arkay inay halis ugu jiraan dhimashada kansarka sanbabada - xaalad halis ah oo loo maleynayo inay tahay in ay noqoto door caan ah. Sidaa daraadeed, CANTOS maxkamad ayaa sidoo kale furay jid cusub oo cilmi baaris ah oo ku saabsan cudurka iyo kansarka.
Munaasabadda ugu weyn ee lagu arkay canakinumab ee CANTOS ee tijaabada ah ayaa ahaa mid yar laakiin tirakoob oo aad u sarreeya oo dhimasho sabab u ah infakshanka. Maadaama ay badanaa lagama maarmaan u tahay jawaab-celinta ka-hortagidda cudurrada faafa, helitaankani lama yaabin.
Waa maxay micnaheeda oo dhan
Waxaa shaki ku jiraa in dacwada CANTOS ay u horseedi doonto isticmaalka baahsan ee canakinumab si loo yareeyo munaasabadaha wadnaha ee dadka khatarta sare leh. Ma aha oo kaliya faa'iidada caafimaad ee ka iman karta canakinumab muuqaal quruxsan, laakiin sidoo kale daawadani waa qaali qaali ah. Daaweynta xaadirka ah ee canakinumab, dadka qaba xaaladaha rheumatologi daran, kharashka qiyaastii $ 200,000 sanadkii. Qeybta ugu caansan ee kaalmada wadnaha ee lagu arko tijaabada CANTOS dhab ahaantii xaq uma lihin isticmaalka daroogada qaaliga ah.
Sidaas awgeed, muhiimadda ay leedahay cilmi-baarista CANTOS maahan in ay aqoonsatay daaweyn cusub oo cusub oo loogu talagalay daaweynta wadnaha, laakiin halkii, waxay aqoonsatay bartilmaameed cusub oo cilmi-baaris ah.
Ilaa iyo hada, hoos u dhigida khatarta wadnaha iyo daaweynta ayaa yaraaday waxoogaa badan oo hoos udhaca kolesteroolka (badanaa oo ay ku jiraan statins), iyo laga yaabee in la xakameeyo dhiig-xinjirowga (oo leh asbirin ). Hadda waxay u muuqataa, si ka badan sidii hore ka hor, in xakamaynta qaybaha gaarka ah ee jawaabta bararka ee gudaha xididdada dhiigga ay sidoo kale yarayn karaan dhacdooyinka dhibaatooyinka wadnaha.
Waxaan fileyn karnaa shirkadaha dawooyinka in ay si dhakhso ah uga faa'iideystaan habkan cusub ee daaweynta, waxayna si weyn u xoojinayaan horumarintooda siyaabaha kale ee xakameyn kara bararka infekshinka. Haddii dadaalkaan uu soo saaro wax kasta sida khubarada badani hadda saadaaliyaan, CANTOS maxkamad ayaa dhab ahaantii ugu dambeyntii loo arkaa in ay tahay guul weyn oo ku saabsan daaweynta cudurrada wadnaha iyo xididada-hadday noqoto mid aan caadi ahayn.
Ereyga
Hadda waxay u muuqataa mid xaqiiqda ah in bararka uu kaalin weyn ka ciyaaro horumarinta atherosclerosis, iyo natiijada dadka qaba xanuunka vascular vasculariser. CANTOS trial ayaa muujisay in daaweynta la beegsanayo ee loogu talagalay dhinacyada gaarka ah ee jawaabcelinta baraarujinta ay si weyn u wanaajin karaan natiijada dadka khatarta sare leh.
Inkastoo canakinumab-dawada u shaqeysa CANTOS tijaabada-marnaba uma baahna isticmaalka baahsan ee cudurada wadnaha, cilmi-baarayaashu waxay hadda sameeyeen jid cusub oo lagu daweeyo cudurkaan. Sannadaha soo socda waxaan filan karnaa inaan maqalno wax badan oo ku saabsan caabuqa sababtoo ah atherosclerosis, iyo daaweynta cusub ee loogu talagalay in la xakameynayo buubankan.
> Ilo:
> Libby P, Ridker PM, Hansson GK, Leducq Transatlantic Network on Atherothrombosis. Caabuqa Atherosclerosis: Laga soo bilaabo Pathophysiology to Practice. J Am Coll Cardiol 2009; 54: 2129.
> Ridker PM, Everett BM, Thuren T, et al. Daaweynta Dabaysha Xanuunada Canakinumab ee Cudurka Atherosclerotic. N Engl J Med 2017; DOI: 10.1056 / NEJMoa1707914.
> Weber C, Noels H. Atherosclerosis: Cudurrada Socda iyo Xeeladaha Khatarta ah. Nat Med 2011; 17: 1410.