I-Xeljanz Yayiqala I-JAK Inhibitor Yavunyelwe e-US; I-Baricitinib Yilandela
I-Baricitinib yi- JAK yomlomo (Janak kinase) inhibitor okumele ithathwe ngokuthi i- arthritis ye- rheumatoid . Esikhathini sokuqala sika-2016, i-baricitinib ithunyelwe ukubuyekezwa okulawulwayo nokuvunyelwa kwemakethe e-US, i-European Union, neJapane. Ikomidi lezokwelapha ze-European Medicine Agency for Human Use lanconywe ukuthi livunyelwe ngoDisemba 2016.
Ngo-February 13, 2017, lesi sidakamizwa savunyelwa ukuba sithengiswe isifo samathambo e-European Union njenge- Olumiant (i-baricitinib) . E-US, i-FDA yamemezela ngoJanuwari 13, 2017 ukuthi ikhulise isikhathi sokubuyekeza sesicelo esisha semithi ye-baricitinib. Isandiso esivunyelwe ukubuyekezwa kwedatha eyengeziwe eyathunyelwa ngemuva kokuthi kwenziwe isicelo sokuqala kwezidakamizwa.
Ngo-Ephreli 14, 2017, i-FDA i-baricitinib eyamangalisa ngokumangalisayo. I-FDA ikhiphe incwadi ephendulayo ephelele echaza ukuthi i-ejensi "ayikwazi ukwamukela isicelo kufomu layo lamanje". I-FDA ithi idatha yokwelashwa eyengeziwe iyadingeka ukuze kunqunywe ukulinganisa okufanele kakhulu. Futhi, idatha eyengeziwe iyadingeka ukuze uqhubeke uveza ukukhathazeka kokuphepha kuzo zonke izingalo zokwelapha. Isikhathi sokubuyiswa kabusha sizolandela izinkulumo ezengeziwe ne-FDA.
Ngaphezu kwalokho, ukuhlolwa kwesigaba 2 kuyaqhubeka okuyinto yokuphenya i-baricitinib ye- systemic lupus erythematosus ne- atopic dermatitis .
Isivivinyo sesi-3 se-baricitinib se- psoriatic arthritis kulindeleke ukuba siqale ngo-2017.
I-Xeljanz Yayiqala I-JAK Inhibitor ye-Rheumatoid Arthritis
I-Xeljanz (tofacitinib) yayiyi-JAK inhibitor yokuqala evunywe yi-FDA ngo-2012 kubantu abadala abanomthelela othomathikhi kuya kwesifo se-rheumatoid esinamandla esasiphendule ngokwanele ku- methotrexate .
Kukhona ama-enzyme amane we-JAK: JAK1, JAK2, JAK3, no-Tyk2. I-Xeljanz ivimbela ngokuyinhloko i-JAK1 ne-JAK3, futhi ithathwa kabili nsuku zonke. Ngokulinganayo, i-baricitinib ivimbela i-JAK1 ne-JAK2 futhi ithathwa kanye nsuku zonke.
Izivivinyo ezine zezigaba ezintathu zeBaricitinib
U-Eli Lilly & Inkampani ne-Incyte Corporation bangabalingani ekuthuthukiseni i-baricitinib. U-Lilly no-Incyte benza izivivinyo ezine zesigaba 3 emitholampilo abahlanganyeli abafundela ngokulinganisela ukuba nesifo samathambo esiyingozi kakhulu.
- Ucwaningo lwe-RA-BUILD - iziguli ezingama-684 ze-rheumatoid arthritis ezinezifo ezisebenzayo zanikezwa ngezigidi ezimbili noma ama-milligram ama-baricitinib, noma i-placebo yamaviki angu-24. Uma kuqhathaniswa ne-placebo, amaqembu amabili we-baricitinib abonise ukuthuthukiswa okuphawulekayo okusekelwe kuma- ACR20 , ACR50, nama-ACR70 amanani okuphendula. Okunye okuphawulekayo kulolu cwaningo kwakuwubufakazi obunama-x-ray bokunciphisa ukuqhubeka kwesifo nge-baricitinib, nokuthi iqiniso lokuthi impendulo ye-baricitinib yenzeke ngokushesha, ngezinye izikhathi ngemuva kwesonto elilodwa.
- I-RA-BEACON - iziguli ezingama-rhumatoid arthritis ezingu-527 ezineempendulo ezinganele kwi- inhibitors eyodwa noma ngaphezulu ze- TNF zazinikezwa ngezigidi ezimbili ze-baricitinib, ama-milligrams ayi-baricitinib, noma i-placebo yamaviki angu-24. Amazinga aphendulayo ephakeme e-ACR20 ayebhekwa emaqenjini womabili we-baricitinib uma kuqhathaniswa ne-placebo. Inzuzo yokwelapha eqinisiwe yenzeke kuphela nge-4 milligrams ye-baricitinib.
- I-RA-BEGIN - iziguli ezingu-584 ezine-arthritis esebenzayo ezihlukunyeziwe noma ezingekho ukwelashwa nge- DMARD yendabuko zanikezwe ngezikhathi ezithile methotrexate monotherapy, ama-milligrams ayi-baricitinib, noma ama-milligrams ayi-baricitinib ane-methotrexate amasonto angama-52. Imiphumela yaba ngcono kakhulu nge-baricitinib monotherapy uma kuqhathaniswa ne-methotrexate monotherapy. Ukwengezwa kwe-methotrexate kwi-baricitinib kwakubonakala kungabathinti kahle inzuzo, nakuba inhlanganisela ibonakala sengathi ihamba kancane ubufakazi bokuthi ukukhula kwezifo ku-x-ray.
- I-RA-BEAM - iziguli ezingu-1307 ezine-arthritis esebenzayo, ezazithola methotrexate yangemuva kodwa ezingazange ziphendule ngokwanele, zanikezwa ama-milligrams angu-4 njalo ngosuku, noma ama-milligram angu-40 Humira (adalimumab) njalo ngesonto, noma i-placebo. Ukuthuthukiswa komtholampilo okuphawulekayo kwakuhlanganiswe ne-baricitinib ngokumelene ne-placebo noma i-Humira.
Abahlanganyeli bokufunda abaqedile i-RA-BUILD, RA-BEGIN, noma i-RA-BEAM bafanelekile ukuba bahlanganyele esifundweni sesandiso, esaziwa njenge-RA-BEYOND. Isifundo sokwandisa siphethe ngokuthi i-milligram 4 ye-baricitinib yayisebenza kahle kakhulu.
Iphrofayela yokuphepha ye-Baricitinib
Ukwaziswa ngokuphepha kwe-baricitinib kwahlanganiswa ngokuhlaziya zonke izivivinyo zokwelashwa kusukela esigabeni 1 kuya kwesigaba sesi-3, kanye nesifundo sokwandisa. Izilingo zazibandakanya iziguli ezingu-3,464 ngokuphelele. Ukulandela ukuvezwa kwe-baricitinib, kwakungekho ukunyuka kwezifweni, izifo ezimbi, izifo ezimbi, izifo ezithathelanayo, noma izenzakalo ezimbi ezibangelwa ukuyeka ukuphuma kwezidakamizwa. Uma kuqhathaniswa ne-placebo kwakukhona ukwenyuka okuphawulekayo kwesilinganiso samagciwane we- herpes zoster eziguli eziphathwe nge-4 milligram dose ye-baricitinib. Ukwelashwa nge-baricitinib kwaxhunyaniswe nezinguquko emazingeni we-hemoglobin, i-lymphocytes, i-transaminases, i-creatine kinase, ne-creinine-kodwa ayikho into ebonakalayo edingekayo yokudinga ukukhishwa kwesidakamizwa.
Izwi elivela
I-JAK inhibitors yiklasi lesithathu le-DMARDS, elibizwa ngokuthi i-molecule encane DMARDS. Ukutholakala kwe-baricitinib kuzohlinzeka ngolunye ukhetho lwezokwelapha lwe-rheumatoid arthritis, uma kuvunyelwe. Lokho kuvunyelwe kulindeleke ngo-2017. Iziguli ezazithola impendulo enganele ngokwemithitrexate, ezinye izidakamizwa ze-DMARD, noma izidakamizwa ze-biologic , zizoba neminye imithi yomlomo njengendlela yokukhetha. Kwezinye iziguli, kungase kube okukhethwa kukho okulula kakhulu futhi kukhethwe izidakamizwa ze-biologic ezizimele noma eziphilayo ezilawulwa ukumnika.
> Imithombo:
> Kuriya, Bindee et al. I-Baricitinib ku-Arthritis Ye-Rheumatoid: Ubufakazi-kuya-date kanye Nokwelapha. Ukuthuthukiswa Kwezokwelapha Emzimbeni We-Musculoskeletal. 2017 Feb; 9 (2): 37-44.
> Smolen, Josef S. et al. Iziphumo ezibhekene neziguli ezivela emkhakheni we-Phase III wokuHlola weBaricitinib ezigulini ezine-Arthritis ye-Rheumatoid kanye nokuphendula okungafanelekile kuma-Biological Agents (RA-BEACON). Ama-Annal of the Rheumatic Diseases. 2017; 76: 694-700.
> Taylor, Peter C. MD, PhD et al. I-Baricitinib ne-Placebo noma i-Adalimumab ku-Arthritis ye-Rheumatoid. I-New England Journal of Medicine. 2017; 376: 652-662. Ngo-February 16, 2017.
> I-US FDA Yandisa Isikhathi Sokubukeza Nge-Baricitinib, i-Rheumatoid Arthritis Treatment. Lilly. NgoJanuwari 13, 2017.
> Izinkinga ze-US FDA Complete Complete Response Letter for Baricitinib. Lilly ne-Incyte nge-BusinessWire. Ngo-Ephreli 14, 2017.