Ingabe i-JAK Inhibitors ikhethwa njengezidakamizwa ze-Biologic?
I-JAK (Janus kinase) inhibitors iyisigaba sezidakamizwa ezisetshenziselwa ukwelapha isifo samathambo . I-JAK inhibitor yokuqala, i- Xeljanz (tofacitinib citrate) , yamukelwa yi-FDA ngomhla kaNovemba 6, 2012. Abanye bayathuthukiswa . Ukuziphendukela kwe-JAK inhibitor njengokwelashwa kwesifo samathambo esibelethweni se-rheumatoid kwavela ezithendeni zokuthuthukiswa kwe-immunology kanye ne-biology yamangqamuzana okwaholela ekuthuthukiseni izidakamizwa ze- biologic .
Ake sihlole indima ye-JAK inhibitors esimisweni sokuzivikela omzimba nasekulawuleni i-arthritis ye-rheumatoid.
Ama-cytokines achazwe
Abantu abaningi abane-arthritis ye-rheumatoid (nezinye izifo ezivuthayo) mhlawumbe babengakajwayele isikhathi sezokwelapha, ama-cytokines , ngaphambi kokuba umuthi wokuqala we-biologic, i- Enbrel (etanercept) , uvunyelwe ngo-1998. Ukuze uqonde ukuthi izidakamizwa ze-biologic zisebenza kanjani, iziguli zithole ukulimala inkambo e-immunology.
Iziguli zafunda ukuthi i-cytokines ngamaprotheni akhiqizwa ngamangqamuzana nokuthi ahileleke ekulawuleni izimpendulo zokuvuvukala . Ama-Cytokines asebenzisana namaseli omzimba omzimba ukulawula impendulo yomzimba ezifweni nokutheleleka-nokuxhumanisa izinqubo ezivamile zeselula emzimbeni. Ama-Cytokines nawo ahileleke ekuphenduleni okungavamile kwe- autoimmune . Kunezinhlobo eziningana ezahlukene ze-cytokines.
Izidakamizwa ze-biologic zenzelwe ukuphazamisa umsebenzi we-cytokine (isib. Ukuvimbela noma ukuvimbela i- TNF (i-tumor necrosis factor) kanye neziningana ze-interleukins (IL-1, IL-6, IL-17, IL-12/23), ukuvimbela isibonakaliso sesibili esidingekayo ukusebenza ku-T-cell, nokuchitha ama- B-cell .
Nakuba izidakamizwa ezihlukahlukene ze-biologic zinemigomo ehlukene emasosheni omzimba, umgomo ufana-ukusika amakhemikhali ase-proinflammatory, ngaleyo ndlela ilawula isifo sofuba .
Imithi encane ye-Molecule ye-Rheumatoid Arthritis
I-JAK inhibitor ayifakwe njengesidakamizwa se-biologic. Esikhundleni salokho, ihlukaniswa njengemfucumfucu encane DMARD (izifo eziguqula izifo eziphikisana nesifo sofuba).
Inhloso ye-JAK inhibitor yindlela ye-JAK eyindlela yokubonisa ephakathi kwamaseli anendima evelele kwinqubo yokuvuvukala ehambisana ne-arthritis ye-rheumatoid. Ngokuqondile, i-JAKs (i-Janus kinases) ingama-enzyme angama-intracellular (okungukuthi, i-cytoplasmic protein tyrosine kinases) ehambisa izimpawu kusuka kuma-receptors amaningi we-cytokine kuya ku-nucleus yamaseli.
Kubikwa ukuthi kunama-kinase angaphezu kuka-500 "kinome" yabantu futhi bahlukaniswa ngemindeni eyisishiyagalombili. Ama-JAK angomndeni we-tyrosine protein kinase-umndeni onamalungu angu-90. Umndeni wakwaJanus kinase (JAK) uhlanganisa TYK2, JAK1, JAK2, neJAK3.
Lapho abacwaningi beqaphela ukuthi indima ebalulekile i-JAKs idlala ekuboniseni i-cytokine, yaba nomqondo oqakathekile wezifundo zempilo. I-Tofacitinib yayiyi-JAK inhibitor yokuqala okufanele ivivinywe ngemithi futhi ivunyelwe isifo se-rheumatoid arthritis. I-Tofacitinib, eyenziwe ngu-Pfizer, Inc., ivimbela i-JAK3 ne-JAK1, ne-JAK2 ngezinga eliphansi. I-Tofacitinib ayithinti kakhulu iTYK2.
Tofacitinib-I-JAK yokuqala Inhibitor evunyelwe i-Rheumatoid Arthritis
I-Tofacitinib (igama lomkhiqizo we-Xeljanz) livunyiwe njengokwelashwa kubantu abadala ngokulinganisela- ku-arthritis esebenzayo yesifo se-rheumatoid eyayinempendulo enganele noma ukungabekezelelani ku- methotrexate .
I-Xeljanz imithi yomlomo, etholakalayo njengephilisi e-5 mg okufanele ithathwe kabili nsuku zonke. Kungathathwa noma ngaphandle kokudla. Kukhona futhi umthamo we-11 mg owodwa-nsuku zonke okhona, obizwa nge-Xeljanz-XR (ukukhululwa okukhulisiwe). I-Xeljanz ingathathwa yedwa (okungukuthi, isetshenziswe njenge-monotherapy), noma ingahlanganiswa ne-methotrexate noma ezinye ze-DMARD ezingekho ze-biologic. I-Xeljanz akufanele isetshenziswe ngezidakamizwa ze-biologic.
Ukuphepha kwe-JAK Inhibitor Izidakamizwa
Njengoba ukuhlolwa kwahlolwa nge-Xeljanz (tofacitinib), abacwaningi baphetha ngokuthi kwakufana nezidakamizwa ze-biologic. Kukhona ingozi eyengeziwe yokwelashwa, okungahle kwenzeke ngokuhlolwa kokusebenza kwesibindi , kanye nekhono le-neutropenia (izinga elincane le-neutrophils, uhlobo lwegciwane legazi elimhlophe), i-hyperlipidemia (lipids ephakanyisiwe noma amafutha egazini), futhi i-serum creatinine ephakanyisiwe ukusebenzisa i-tofacitinib.
Isixwayiso se-Black Box sasidinga njengengxenye yokwamukelwa nokulayishwa kwe-tofacitinib ukuxwayisa ngalezi zingozi ezibi kakhulu.
I-Baricitinib
I-Baricitinib yayiyesibili i -JAK inhibitor ukuhambisa i-NDA (Isicelo Esisha seDrug) ku-FDA ngoJanuwari 2016. I-FDA iye yandise isikhathi sokubuyekeza iBaricitinib ukuvumela isikhathi sokubukwa kwedatha eyengeziwe ehlinzekwa ngumenzi wezidakamizwa, uLily no-Incyte. Idatha eyengeziwe yanikezwa ngokuphendula isicelo se-FDA Ulwazi. Ulwazi olwengeziwe lubonakala njengesichibiyelo esikhulu ku-NDA yangempela futhi lengeza izinyanga ezintathu esikhathini sokubuyekeza.
Ngo-December 2016, iKomiti Yezokwelapha Yezokwelapha ze-European (Medicine Products for Human Use) (CHMP) yakhuthaza ukunikeza imvume yokuthengisa eMnyangweni we-European Union (EU) we-Olumiant (ibicitinib). I-Baricitinib yanconywa ukwelashwa kwabantu abadala abanomthelela olwazini wezifo zesifo sofuba esingasebenzi kahle abangazange basabele ngokwanele, noma abangakwazi ukubekezelela izidakamizwa eziphikisana nezifo eziguqukayo (DMARD) noma ngaphezulu.
I-Baricitinib iyisimiso se-JAK1 / 2 yomlomo esisodwa yansuku zonke esiboniswe ukwelashwa kokulinganisela kwesifo samathambo esibi kakhulu. Idatha yokuhlolwa komtholampilo ibonise ukuthuthuka okuphawulekayo ebuhlungu, ukukhathala, ukusebenza ngokomzimba, kanye nempilo ehlobene nempilo ehlobene neziguli ezingaphatulwanga ngaphambili kanye nalabo abahluleke kwezinye izidakamizwa.
Izwi elivela
Ukuze uphinde uphinde, ama-JAK inhibitors ahlukaniswa njengama-DMARD amancane, hhayi izidakamizwa ze-biologic. Umehluko omkhulu ukuthi i-JAK inhibitors isebenza ngokweqile (ngaphakathi kwamaseli) kanye nezidakamizwa ze-biologic zinemigomo ye-extracellular (isb., Ama-receptors ebusweni bamaseli). Kanti futhi, i-JAK inhibitors yizidakamizwa zomlomo, kuyilapho izinto eziphilayo zijova noma zilawulwa ukukhipha.
Njengoba abantu abane-arthritis ye-rheumatoid akubona bonke abasabelayo ekwelapheni, kubalulekile ukuthuthukisa nokwenza izinketho zokwelapha ezintsha. Ngokungeziwe ku-tofacitinib ne-baricitinib okukhulunywe ngayo ngenhla, izivivinyo zesigaba se-III ziqhubeka nokusebenzisa i-filgotinib ne-ABT-494-kokubili i-JAK1 inhibitors.
> Imithombo:
> Furst, Daniel E., MD. Sibutsetelo se-Biologic Agents kanye ne-Kinase Inhibitors ku-Rheumatic Diseases. Kusesikhathini. Kubuyekezwe ngomhla ka-2 Februwari, 2017.
> McInnes, Iain B., PhD. Ama-cytokine Networks ku-Rheumatic Diseases: Imiphumela yeTherapy. Kusesikhathini. Kubuyekezwe u-Novemba 5, 2015.
> Nakayamada, S. et al. Intuthuko yakamuva ku-JAK Inhibitors ye-Treatment of Rheumatoid Arthritis. BioDrugs. Okthoba 2016.
> O'Shea, uJohn J. et al. I-Janus Kinase Inhibitors ku-Autoimmune Diseases. Ama-Annal of the Rheumatic Diseases. April 2013.
> Elvidge, uSuzanne. Isinqumo se-FDA sokulahla ngesifo se-Lilly ne-Incyte sika-Arthritis Drug. BiopharmaDIVE. NgoJanuwari 17, 2017.