Na JAK Inhibitors e ikhethang e le Biologic Drugs?
JAK (Janus kinase) inhibitors ke sehlopha sa lithethefatsi tse sebelisetsoang ho phekola ramatiki ea lefu la masapo . JAK inhibitor ea pele, Xeljanz (tofacitinib citrate) , e ile ea amoheloa ke FDA ka la 6 November, 2012. Tse ling li nts'etsopele. JAK inhibitor ea ho iphetola ha lintho e le phekolo ea ramatiki ea lefu la rumatoid e ile ea hlaha ka likhahla tsa tsoelo-pele ea immunology le baeloji ea limolek'hule tse ileng tsa lebisa tlhokomelong ea lithethefatsi tsa biologic .
A re ke re hlahlobeng karolo ea JAK inhibitors tsamaisong ea ' mele ea ho itšireletsa mafung le ho laola ramatiki ea lefu la masapo.
Li-cytokines li Hlalosoa
Batho ba bangata ba tšoeroeng ke ramatiki ea lefuba (le mafu a mang a bakoang ke ho ruruha) mohlomong ba ne ba sa tloaelehe ka nako ea bongaka, li-cytokines , pele sethoba sa pele sa biologic, Enbrel (etanercept) , se amoheloa ka 1998. E le ho utloisisa hore na lithethefatsi tsa biologic li sebetsa joang, nete ho immunology.
Bakuli ba ithutile hore li-cytokine ke liprotheine tse hlahisoang ke lisele le hore li ameha ho laola likarabo tsa ho ruruha . Li-cytokines li sebelisana le lisele tsa 'mele tsa ho itšireletsa mafung ho laola tsela eo' mele o arabelang ka eona ho mafu le tšoaetsano-le ho buisana le mekhoa e tloaelehileng ea lik'hamera 'meleng. Li-cytokines li boetse li ameha likarolong tse sa tloaelehang tsa likarabo. Ho na le mefuta e sa tšoaneng ea li-cytokine.
Lithethefatsi tsa likokoana-hloko li bōpiloe ho thibela mosebetsi oa cytokine (mohlala, ho thibela kapa ho thibela TNF (tumor necrosis factor) le tse 'maloa tsa li-interleukin (IL-1, IL-6, IL-17, IL-12/23), ho thibela pontšo ea bobeli e hlokahalang bakeng sa ts'ebetso ea T-cell, le ho senya lisele tsa B.
Le hoja lithethefatsi tse sa tšoaneng tsa li-biologic li na le sepheo se fapaneng le tsamaisong ea 'mele ea ho itšireletsa mafung, sepheo se tšoana-ho senya limolek'hule tse hlahisang matla, ka tsela eo li laola lefu la ho ruruha .
Meriana e nyenyane ea likolek'hule bakeng sa ramatiki ea ramatiki
JAK inhibitor ha e hlalosoe e le lithethefatsi tsa biologic. Ho e-na le hoo, e khetholloa e le molek'hule e nyenyane DMARD (meriana e loantšang mafu-anti-rheumatic drug).
Sepheo sa JAK inhibitor ke tsela ea JAK e leng tsela ea ho paka e ka hare ho lisele tse nang le karolo ea bohlokoa mosebetsing oa ho ruruha o amanang le ramatiki ea lefu la masapo. Ka ho khetheha, JAKs (Janus kinases) ke li-enzyme tse entracellular (ke hore, cytoplasmic protein tyrosine kinases) tse fetisang lipontšo ho tloha li-receptor tse ngata tsa cytokine ho ea fihla motseng oa lisele.
Ho tlalehoa hore ke kinase tse fetang 500 "kinome" ea batho 'me li arotsoe ka malapa a robeli. Ma-JAK a lelapeng la tyrosine protheine kinase-lelapa le nang le litho tse 90. Lelapa la Janus kinase (JAK) le kenyelletsa TYK2, JAK1, JAK2, le JAK3.
Hang ha bafuputsi ba hlokomela hore karolo ea bohlokoa eo JAKs e e bapalang ka ho bontša pono ea cytokine, e ile ea e-ba sepheo sa thuto ea bongaka. Tofacitinib e ne e le JAK inhibitor ea pele e hlahlojoang ke lingaka 'me e amoheloa bakeng sa ramatiki ea mafu. Tofacitinib, e entsoeng ke Pfizer, Inc., e thibela JAK3 le JAK1, le JAK2 ka tekanyo e nyane. Tofacitinib ha e ama TYK2 haholo.
Tofacitinib-Lekhetlo la pele la JAK Inhibitor le amohelehang bakeng sa ramatiki ea ramatiki
Tofacitinib (lebitso la lebitso la Xeljanz) le ile la amoheloa e le phekolo ea batho ba baholo ka mokhoa o itekanetseng-ho matlafatsa ramatiki ea lefu la masapo a neng a e-na le karabelo e sa lekaneng kapa ho se mamellane ho methotrexate .
Xeljanz ke meriana ea molomo, e fumaneha joaloka pilisi e 5 mg e lokelang ho nkoa habeli ka letsatsi. E ka nkoa ka ntle kapa ntle le lijo. Hape ho na le lethal dose ea 11 mg hang-letsatsi e fumanehang, e bitsoang Xeljanz-XR (tokoloho e atolositsoeng). Xeljanz e ka nkoa e le mong (e leng, e sebelisoang e le monotherapy), kapa e ka kopanngoa le methotrexate kapa tse ling tsa DMARD tse ling tse sa bonoeng. Xeljanz ha ea lokela ho sebelisoa ka lithethefatsi tsa biologic.
Tšireletseho ea JAK Inhibitor Lithethefatsi
Ha ts'ireletso e hlahlojoa mabapi le Xeljanz (tofacitinib), bafuputsi ba phethile hore ho ne ho tšoana le lithethefatsi tsa biologic. Ho na le kotsi e eketsehileng ea tšoaetso, e ka 'nang ea e-ba e sa tloaelehang ka liteko tsa sebete , le matla a neutropenia (tekanyo e tlaase ea neutrophils, mofuta oa sele e tšoeu ea mali), hyperlipidemia (lipids e phahameng kapa mafura a mali), le serum creatinine e phahameng ho sebelisa tofacitinib.
Tlhokomeliso ea Letšoao le Letšo le ne le hlokoa e le karolo ea tumello le ho ngolla tofacitinib ho lemosa ka liphello tse bohloko tse mpe tsena.
Baricitinib
Baricitinib e ne e le oa bobeli JAK inhibitor hore a fane ka NDA (Tlhahlobo e Ncha ea Meriana) ho FDA ka January 2016. FDA e ekelitse nako ea ho hlahloba Baricitinib ho lumella nako ea ho hlahloba lintlha tse eketsehileng tse fanoeng ke moetsi oa lithethefatsi, Lily le Incyte. Boitsebiso bo eketsehileng bo fanoe ka karabo ea tlhahiso ea FDA ea tlhahisoleseding. Boitsebiso bo eketsehileng bo nkoa e le phetoho e kholo ea NDA ea pele 'me e eketsa likhoeli tse 3 nakong ea ho hlahloba.
Ka December 2016, Komiti ea European Medicines Agency ea Meriana ea Meriana ea Tšebeliso ea Botho (CHMP) e khothalletsa ho fana ka tumello ea ho rekisetsa Europe Union (EU) bakeng sa Olumiant (baricitinib). Baricitinib e buelloa bakeng sa phekolo ea batho ba baholo ba nang le ramatiki ea methapo ea mafu e feteletseng le e matla haholo ba sa kang ba arabela ka mokhoa o lekaneng, kapa ba sitoang ho mamella e le 'ngoe kapa tse ling tse ngata tsa ho loantša mafu a li-anti-rheumatic drugs (DMARD).
Baricitinib ke lehlakoreng la letsatsi le leng le le leng la JAK1 / 2 inhibitor ea molomo o bontšitse ho phekoloa ha masapo a matla a lefu la masapo. Litlaleho tsa liteko tsa meriana li bontšitse ntlafatso e kholo mahlomoleng, mokhathala, mosebetsing, le boleng bo amanang le bophelo bo botle bathong ba neng ba sa phekoloe le ho ba ileng ba hlōleha lithethefatsi tse ling.
Lentsoe le Tsoang ho
Ho pheta-pheta, JAK inhibitors li aroloa e le li-molecule tse nyenyane tsa DMARD, eseng lithethefatsi tsa biologic. Phapang e ka sehloohong ke hore JAK inhibitors e sebetsa intracellularly (ka hare ho lisele) le lithethefatsi tsa biologic li na le lipeo tsa extracellular (mohlala, li-receptors tse ka holim'a lisele). Hape, JAK inhibitors ke lithethefatsi tsa molomo, ha li-biologics li ka kenngoa meriana kapa li tsamaisoa ke infusion.
Kaha batho ba nang le lefu la ramatiki ha ba na karabo e tšoanang le ea phekolo, ke habohlokoa ho ntshetsa pele le ho etsa mekhoa e mecha ea phekolo. Ho phaella ho tofacitinib le baricitinib tseo ho builoeng ka tsona ka holimo, liteko tsa kemiso ea phalliso III li ntse li tsoela pele ho sebelisa filgotinib le ABT-494-tse peli tsa JAK1 inhibitors.
> Mehloli:
> Furst, Daniel E., MD. Tlhahlobo ea Biologic Agents le Kinase Inhibitors ho Rheumatic Diseases. E maemong. E fetotsoe ka la 2 February, 2017.
> McInnes, Iain B., PhD. Li-Cytokine Networks ka Rheumatic Diseases: Liphello tsa Therapy. E maemong. E fetotsoe ka la 5 November, 2015.
> Nakayamada, S. et al. Khatelo-pele ea morao-rao ho JAK Inhibitors bakeng sa Phekolo ea Ramatiki ea Ramatiki. BioDrugs. October 2016.
> O'Shea, John J. le al. Janus Kinase Inhibitors ka Maloetse a Ikhethang. Annals ea Rheumatic Diseases. April 2013.
> Elvidge, Suzanne. Tlhaloso ea FDA ea ho fokotsa lithethefatsi ho Lilly le Incyte's Arthritis Drug. BiopharmaDIVE. La 17 January, 2017.