Ko JAK Inhibitors Inosarudza se Biologic Zvinodhaka?
JAK (Janus kinase) inhibitors inhengo yezvinodhaka zvinoshandiswa kurapa rheumatoid arthritis . Yoyakatanga JAK inhibitor, Xeljanz (tofacitinib citrate) , yakagamuchirwa neDFA musi waNovember 6, 2012. Vamwe vari mukugadzirwa. Kugadziriswa kweJAK inhibitor sekurapa kwehutemaid arthritis kwakauya kune zvitsva zvekufambira mberi kwekuzivikanwa kweumunology uye molecular biology iyo yakatungamirira pakuvandudzwa kwezvinodhaka zvebiologic .
Ngationgororei basa reJAK inhibitors muzvirwere zvemuviri uye mune mukuronga rheumatoid arthritis.
Cytokines Inotsanangurwa
Vanhu vakawanda vane rheumatoid arthritis (nezvimwe zvirwere zvinopisa) zvichida vakanga vasina kujaira nguva yezvechiremba, cytokines , musati wamboshandisa biologic drug, Enbrel (etanercept) , yakagamuchirwa muna 1998. Kuti uzonzwisisa kuti biologic zvinodhaka zvinoshanda sei, varwere vanoparara course in immunology.
Varwere vakadzidza kuti cytokines mapuroteni anobudiswa nemasero uye kuti anobatanidzwa mukugadzirisa kupindura kwezvokuvhiringidza . Kurotokine inobatanidza nemasikirini emasero kuti atungamirire kupindura kwomuviri kune zvirwere uye utachiona-uye kuratidzira zviyero zvemajirusi mumutumbi. Cytokines inobatanidzwawo mumhinduro dzisina kukodzera. Kune marudzi akasiyana-siyana e-cytokines.
Biologic zvinodhaka zvakasikwa kuti zvipindire neytokine basa (p., Kuvhara kana kudzivisa TNF (tumor necrosis factor) uye yakawanda ye-interleukins (IL-1, IL-6, IL-17, IL-12/23), kudzivisa chiratidzo chechipiri chinodiwa che T-cell activation, uye kubvisa B-masero .
Kunyange zvazvo zvakasiyana-siyana zvebiologic zvinodhaka zvakasiyana-siyana mukati mezvirwere zvemuviri, chinangwa chacho chakafanana-kukonzera pasi zvinopisa zvinokonzera mamolekemu, nokudaro kudzora chirwere cherheumatic .
Minimum Molecule Medication for Rheumatoid Arthritis
A JAK inhibitor haisi iyo inonzi biologic drug. Pane kudaro, inorondedzerwa sediki duku DMARD (chirwere-chinorwisa anti-rheumatic drug).
Chinangwa cheJAK inhibitor ndiyo nzira yeJAK iyo inoratidza nzira iri mukati memasero ayo ane basa rakakurumbira mukuvhiringidza kunobatanidza nerheumatoid arthritis. Kunyanya, JAKs (Janus kinases) inonzi intracellular enzymes (kureva, cytoplasmic protein tyrosine kinases) iyo inotumira zviratidzo kubva kune dzakawanda dzektokine receptors kusvika kumusi wemasero.
Iko kunonzi inopfuura mazana mashanu kinases muvanhu "kinome" uye iyo yakakamurwa kuva mhuri masere. IJAKs iri mumhuri ye tyrosine protein kinase-mhuri ine mamamiri 90. Mhuri yaJanus kinase (JAK) inosanganisira TYK2, JAK1, JAK2, uye JAK3.
Apo imwe tsvakurudzo yakaona kuti basa rinokosha reJAKs rinotarisa mukujekesa kwechitokine, vakava kunyanya kutsvaga mune zvidzidzo zvechiremba. Tofacitinib ndiye wokutanga JAK inhibitor kuti aongororwe muchipatara uye anogamuchirwa kuti awane rheumatoid arthritis. Tofacitinib, iyo inogadzirwa naPfizer, Inc., inhibits JAK3 uye JAK1, uye JAK2 kusvika pamwero muduku. Tofacitinib haina kuchinja TYK2.
Tofacitinib-Yokutanga JAK Inhibitor Yakagamuchirwa neRheumatoid Arthritis
Tofacitinib (zita rechiratidzo Xeljanz) rakagamuchirwa senzira yekurapa kune vanhu vakuru nemwero-kusvika kune zvakanyanya-inoshanda rheumatoid arthritis iyo yakanga isina kukwana kana kupesana kwe methotrexate .
Xeljanz imishonga yemuromo, inowanikwa se 5 mg piritsi inotorwa kaviri zuva rimwe nerimwe. Inogona kutorwa pamwe kana kuti isina zvokudya. Kunewo 11 mg kamwe-zuva rega reta inowanika, inonzi Xeljanz-XR (yakasunungurwa yakawedzerwa). Xeljanz inogona kutorwa yoga (kureva, inoshandiswa se monotherapy), kana inogona kusanganiswa ne methotrexate kana zvimwe zveimwe DMARD isiri-biologic. Xeljanz haifaniri kushandiswa nemishonga ye biologic.
Kudzivirira kweJAK Inhibitor Zvinodhaka
Sezvo kuchengetedzwa kwakaongororwa maererano neXeljanz (tofacitinib), vatsvakurudzi vakapedzisa kuti yakafanana nemishonga ye biologic. Pane huwandu hwehutachiona hwehutachiona, hunogona kusakanganiswa nechiropa chekushanda , uye inogona kuve neutropenia (pasi shoma ye neutrophils, rudzi rwechichena chemuviri weropa), hyperlipidemia (yakakwirira lipids kana mafuta muropa), uye sarum creatinine yakakwirira tofacitinib kushandiswa.
A Black Box nyevero yaidiwa sechikamu chekubvumirwa nekunyora kwepafacitinib kuti inyeverwe nezvemigumisiro iyi yakaipa.
Baricitinib
Bharicitinib ndiye wechipiri JAK inhibitor kuisa NDA (New Drug Application) kune FDA munaJanuary 2016. FDA yakawedzera nguva yekudzokorora yeBaricitinib kuti ipe nguva yekudzokororwa kwemamwe mashoko anopiwa nemuiti wezvinodhaka, Lily neIncyte. Izvo zvinyorwa zvakapiwa zvakapiwa mukupindura kwekuda kweRA Information Information. Izvo humwe ruzivo runowanikwa sechirongwa chikuru chepakutanga NDA uye inowedzera mwedzi mitatu kusvika panguva yekuongorora.
Muna December 2016, European European Medicines Agency Committee yemishonga yemishonga yevanhu (CHMP) yakakurudzira kupa mvumo yekutsvaga muEuropean Union (EU) yeOlumiant (baricitinib). Bharicitinib yakakurudzirwa kuti kurapwa kwevanhu vakuru vaenzanise kuti vave nehutachiona hwehutachiona rwesarthritis vasina kupindura zvakakwana, kana kuti vasingakwanisi kubvumira imwe kana kupfuura zvirwere-kuchinja zvinorwisa rheumatic drugs (DMARDs).
Bharicitinib ishoko rimwechete-zuva rimwe nerimwe JAK1 / 2 inhibitor rinoratidzira kuti kurapwa kwekuenzanisa kusvika kune yakaoma rheumatoid arthritis. Chipatori chekuongorora dambudziko rakaratidza kuwedzera kwakanyanya mukurwadziwa, kuneta, kuita muviri, uye hutano hwehutano hwehutano hwevatano vasati vashandurwa uye kune avo vakundikana mamwe mishonga.
Shoko Rinobva
Kuti udzoke zvakare, JAK inhibitors inorondedzerwa sediki duku DMARDs, kwete biologic zvinodhaka. Chinokosha chikuru ndechokuti JAK inhibitors inoshanda intracellularly (mukati memasero) uye biologic zvinodhaka zvinowedzera zvishoma (semuenzaniso, zvinogamuchirwa pamusoro pemasero). Uyezve, JAK inhibitors ndeyemishonga yemuromo, nepo biologics iri injectable kana inoshandiswa nekodzero.
Sezvo vanhu vane rheumatoid arthritis havasi vose vane mhinduro imwe chete mukurapwa, zvinokosha kukura nekuita mawaniro matsva ekurapa matsva. Mukuwedzera kune tofacitinib uye baricitinib iyo yakakurukurwa pamusoro apa, zvipatara zvechikamu chechitatu III zvinowedzera kushandisa filgotinib uye ABT-494-zvose JAK1 inhibitors.
> Sources:
> Furst, Daniel E., MD. Maererano neBioologic Agents uye Kinase Inhibitors muRheumatic Diseases. Kusvika pari zvino. Yakavandudzwa paFebruary 2, 2017.
> McInnes, Iain B., PhD. Cytokine Networks muRheumatic Diseases: Zvinokonzerwa neTherapy. Kusvika pari zvino. Yakapedzwa musi waNovember 5, 2015.
> Nakayamada, S. et al. Kufambira mberi kwekupedzisira muJAK Inhibitors nokuda kweKurapwa kweRheumatoid Arthritis. BioDrugs. October 2016.
> O'Shea, John J. et al. Janus Kinase Inhibitors muAimotemune Zvirwere. Annals weRheumatic Diseases. April 2013.
> Elvidge, Suzanne. FDA Inonoka Chisarudzo paLilly uye Incyte's Arthritis Drug. BiopharmaDIVE. January 17, 2017.