Miyaa JAK Inhibitors lagu Xushay Mukhaadaraadka Biyolojiga?
JAK (Janus kinase) xannibaadayaasha waa qayb ka mid ah daawooyinka loo isticmaalo daaweynta rheumatoid arthritis . JAK horjooge ee ugu horreeya, Xeljanz (tofacitinib citrate) , ayaa waxaa ansaxiyay FDA November 6, 2012. Qaar kalena waa horumar. Kalkalinta JAK inhibitor ah sida daweyn loogu talagalay rheumatoid arthritis-ka ayaa ka soo baxay cidhib-tirka horumarinta ee hab-dhiska iyo bioloji-biyoodka kaas oo horseeday horumarinta daroogooyinka bayoloji .
Aynu sahaminno doorka JAK-da ee ku jira habka difaaca jirka iyo maareynta rheumatoid arthritis.
Cytokines Explained
Dadka badankooda qaba rheumatoid arthritis (iyo cudurrada kale ee caabuqa) waxay u badan yihiin in aysan aqoonin ereyga caafimaadka, cytokines , ka hor daawada ugu horreysa, Enbrel (etanercept) , ayaa la ansixiyey 1998. Si loo fahmo sida daroogada bayoolojigu u shaqayso, bukaanadu waxay heleen shil koorsada ku jirta immunology.
Bukaan-socodka waxay barteen in cytokine ay yihiin borotiino ay soo saaraan unugyo iyo in ay ku lug leeyihiin xakamaynta jawaabaha bararka . Cytokines waxay la macaamilaan unugyada difaaca jirka si ay u hagaajiyaan jawaabaha jidhka ee cudurada iyo caabuqa-iyo in ay dhexdhexaadiyaan hababka caadiga ah ee unugyada jirka. Cytokines ayaa sidoo kale ku lug leh jawaabo aan caadi ahayn. Waxaa jira noocyo kala duwan oo cyokokin ah.
Daawooyinka bayoolojiga ah ayaa loo abuuray inay farageliyaan hawlaha cytokine (sida, in la joojiyo ama lagu xakameeyo TNF (cirridka necrosis) iyo dhowr ka mid ah interleukins (IL-1, IL-6, IL-17, IL-12/23), si looga hortago calaamadda labaad ee looga baahanyahay hawlgalka T-cell, iyo in la bakhtiiyo B-unugyada .
Inkastoo daawooyinka nafleyda ee kala duwan ay bartilmaameedyo kala duwan ku jiraan nidaamka difaaca jidhka, yoolka ayaa la mid ah - si loo yareeyo hoos u dhaca miyir-beelka, taas oo xakameysa cudurka rheumatiska .
Daawooyinka Molecule Smalling for Rheumatoid Arthritis
JAK horjooge 'JAK inhibitor' laguma sifeeyo daroogada bayoloji. Taa baddalkeeda, waxaa loo qoondeeyey sidii loo yareeyo DMARD yaryar (daawo-beddelidda daroogada ladagaallanka ah).
Bartilmaameedka JAK inhibitor waa jihada JAK oo ah waddo isbeddel ah oo ku yaala gudaha unugyada kuwaas oo leh door caan ah geedi-socodka bararka ee la xiriira rheumatoid arthritis. Gaar ahaan, JAKs (Janus kinases) waa enzymes intracellular (ie, kinones tyrosine kinetic cytoplasmic) kuwaas oo gudbiya calaamadaha ka soo baxa cytokin badan si nukleus ee unugyada.
Waxaa lagu soo wariyay in ka badan 500 kinase ah ee "kinome" oo ay u qaybsan yihiin siddeed qoys. JAK-yada waxay ku jiraan qoysaska kinase-protein kinase-qoys ah oo leh 90 xubnood. Qoyska Janus kinase (JAK) waxaa ka mid ah TYK2, JAK1, JAK2, iyo JAK3.
Marka cilmi-baarayaashu xaqiiqsadeen doorka muhiimka ah ee JA-yadu ka ciyaaraan cytokine signaling, waxay noqdeen kuwo badan oo diiradda saaraya daraasad kiliinik ah. Tofacitinib wuxuu ahaa jakadii ugu horeysay ee JAK-da si loo baadho oo loo ansixiyo rheumatoid arthritis. Tofacitinib, oo uu soo saaro Pfizer, Inc., wuxuu xakameynayaa JAK3 iyo JAK1, iyo JAK2 si aad u yar. Tofacitinib ma saamaynayso TYK2.
Tofacitinib-JAK-Kacbeedka Ugu Horeeya ee La Oggoley Xanuunka Rheumatoid Xanuunka
Tofacitinib (magaca calaamadda Xeljanz) ayaa loo ansixiyey inuu yahay daaweyn loogu talagalay dadka qaangaarka ah oo si dhexdhexaad ah u-socda rheumatoid arthritis-ka firfircooni leh kaas oo ku yeeshay jawaab aan ku filneyn ama aan loo dulqaadan karin daawada methotrexate .
Xeljanz waa daawo afka ah, oo la heli karo sida 5 mg oo kiniin ah oo loo qaato laba jeer maalintii. Waxaa laga yaabaa in la qaato ama aan lahayn cunto. Waxaa sidoo kale jira 11 mg oo qiyaasta hal mar ah oo la heli karo, oo loo yaqaan Xeljanz-XR (sii-deyn dheeri ah). Xeljanz ayaa keligiis loo qaadan karaa (ie, loo isticmaalo daaweynta monotherapy), ama waxaa lagu dari karaa daawada methotrexate ama qaar ka mid ah kuwa DMON ee kale. Xeljanz waa in aan loo isticmaalin daawooyinka nafleyda.
Nabadgelyada daawooyinka JAK Inhibitor
Maaddaama ammaanka la qiimeeyay ee la xidhiidha Xeljanz (tofacitinib), cilmi-baarayaashu waxay soo gabagabeeyeen inay la mid tahay daawooyinka bayolojiga. Waxaa jira khatar kor u kaca infakshannada, baaritaannada laga yaabo in ay ku dhacaan baaritaanka shaqada beerka , iyo suurtogalka ah nutropenia (heerka hoose ee neutrophils, nooca unugyada dhiigga cad), hyperlipidemia (lipids ama dufanka dhiigga sareeya), iyo kareemka serum sare leh isticmaalka tofacitinib.
Digniinta A Black Box ayaa looga baahan yahay iyada oo qayb ka ah oggolaanshaha iyo calaamadeynta tofacitinib si looga digo dhibaatooyinkan halista ah.
Baricitinib
Baricitinib wuxuu ahaa JAK inhibitor labaad si uu u soo gudbiyo Foomka NDA (Codsiga Cusub ee Cusub) FDA bishii Janaayo 2016. FDA waxay kordhisay xilliga dib u eegista Baaricininib si loogu ogaado waqtiga dheeraadka ah ee dib u eegista xogta dheeraadka ah ee ay bixisay daroogada, Lily iyo Incyte. Xogta dheeraadka ah waxaa lagu bixiyay jawaabta codsiga Warbixinta FDA. Macluumaadka dheeraadka ah waxaa loo arki karaa isbedel weyn oo loogu talagalay NDA asalka ah waxayna ku darsataa 3 bilood xilliga dib u eegista.
Bishii Disembar 2016, Guddiga Caafimaadka ee Yurub ee Maqaalada Caafimaadka ee loogu talagalay alaabta Isticmaalka Bani-aadamka (CHMP) ayaa kugula taliyay bixinta oggolaanshaha suuq-galka Midowga Yurub (EU) ee Olumitic (baricitinib). Baricitinib ayaa lagu taliyay daawaynta dadka qaangaarka ah ee leh rheumatoid arthritis-ka firfircoon ee aan si fiican ugu jawaabin, ama aan awoodin inay u dulqaataan hal ama in ka badan oo ah daawooyinka ladagaallanka dawooyinka ladagaallanka ah (DMARDs).
Baricitinib waa hal mar maalin walba JAK1 / 2 inhibitor leh oo lagu tilmaamayo daaweynta arthritis-ka dhexdhexaad ah ama mid daran. Macluumaadka tijaabada caafimaadka ayaa muujiyey kor u kaca ah xanuun, daal, shaqo jireed, iyo tayada jireed ee la xiriirta caafimaadka jirka ee bukaannada aan hore loo daaweyn iyo kuwa ku guuldaraystay daawooyinka kale.
Ereyga
Si loo celiyo, JAK-celiyeyaasha waxaa lagu sifeeyay maadi yar yar DMARDs, ma ahan daroogo noololoji. Farqiga ugu muhiimsani waa in JAK-celiyeyaasha ka shaqeeyaan gudaha (unugyada gudaha) iyo daroogooyinka bayoolojiga ah waxay leeyihiin bartilmaameedyo ka baxsan (tusaale ahaan, kuwa soo dhaweeyaha korka ee unugyada). Sidoo kale, JAK hortagayaasha waa daawooyinka afka laga qaato, halka bayoolajiyadu ay yihiin kuwo laysku duro ama ay qaadaan faleebo.
Maadaama dadka qaba rheumatoid arthritis-ku dhammaantood aaney helin jawaab isku mid ah daaweynta, waxaa muhiim ah in la hormariyo oo la sameeyo fursado daaweyn oo cusub. Marka laga soo tago tofacitinib iyo baricitinib kuwaas oo laga wada hadlay kor-u-qaadista, tijaabooyinka wajiga koowaad ee daaweynta ayaa sii socota iyada oo la adeegsanayo filgotinib iyo ABT-494-kuwa JAK1 labadaba.
> Ilo:
> Furst, Daniel E., MD. Warbixin kooban oo ku saabsan Dhakhaatiirta Biyoolajiyeyaasha iyo Kinasehibayaasha Kansarka ee Rheumatic Cudurada. UpToDate. La daabacay Febraayo 2, 2017.
> McInnes, Iain B., PhD. Cytokine Networks ee Cudurrada Rheumatic ah: Saameynta daaweynta. UpToDate. Dib loo cusbooneysiiyay November 5, 2015.
> Nakayamada, S. et al. Horumarka ugu dambeeyay ee JAK Inhibitors ee Daaweynta Rheumatoid Arthritis. Biyo daroogo. Oktoobar 2016.
> O'Shea, John J. et al. Janus Kinase Nadaafadayaasha Cudurrada Maqnaanshaha. Annals of Cudurada Rheumatic. Abriil 2013.
> Elvidge, Suzanne. FDA waxay dib u dhigtaa Go'aanka ku saabsan Lilly iyo Incyte's Drug Drug. BiopharmaDIVE. Janaayo 17, 2017.