Kodi JAK Inhibitors Amadziwika Ngati Biologic Mankhwala?
JAK (Janus kinase) inhibitors ndi gulu la mankhwala ogwiritsidwa ntchito pofuna kuchiza nyamakazi ya nyamakazi . JAK inhibitor yoyamba, Xeljanz (tofacitinib citrate) , inavomerezedwa ndi FDA pa November 6, 2012. Ena ali pa chitukuko. Kusinthika kwa JAK inhibitor monga chithandizo cha nyamakazi ya nyamakazi kunabwera pazitsamba za kupita patsogolo kwa maumunology ndi biology zomwe zinapangitsa kuti pakhale mankhwala osokoneza bongo .
Tiyeni tifufuze mbali ya ma JAK inhibitors mu chitetezo cha mthupi komanso poyang'anira matenda a nyamakazi.
Ndemanga za Cytokines
Anthu ambiri omwe ali ndi matenda a nyamakazi (ndi matenda ena opweteka) mwina sanali odziwika ndi mankhwala, cytokines , chisanafike mankhwala oyamba a biologic, Enbrel (etanercept) , adavomerezedwa mu 1998. Kuti amvetse momwe mankhwala osokoneza bongo amachitira, odwala akuwonongeka maphunziro mu immunology.
Odwala adziŵa kuti cytokini ndi mapuloteni omwe amapangidwa ndi maselo ndipo amathandizira kuthetsa kuyankhidwa kotupa . Ma cytokines amagwirizana ndi maselo a chitetezo cha mthupi kuti athetse momwe thupi limayankhira ku matenda ndi matenda-komanso kuti athetsere njira zamagetsi zowonongeka m'thupi. Ma Cytokines amathandizanso kuyankha molakwika. Pali mitundu yambiri ya cytokini.
Mankhwala a biologic apangidwa kuti asokoneze ntchito ya cytokine (mwachitsanzo, kulepheretsa kapena kuletsa TNF (chotupa cha ntherosiyo factor) ndi angapo a interleukins (IL-1, IL-6, IL-17, IL-12/23), kuti ateteze chizindikiro chachiwiri chofunika kuti T-selo ikugwiritsidwe ntchito, ndi kuchepetsa maselo a B.
Ngakhale mankhwala osokoneza bongo osiyanasiyana ali ndi zifukwa zosiyanasiyana pa chitetezo cha m'thupi, cholinga chake ndi chimodzimodzi-kuchepetsa ma molekyulu, motero imayambitsa matenda ozunguza bongo .
Mankhwala Ochepa a Mamolekyu a Matenda a Khunyu
JAK inhibitor sichidziwika kuti ndi mankhwala osokoneza bongo. M'malo mwake, amadziwika ngati kamulukidwe kakang'ono ka DMARD (mankhwala osinthira anti-rheumatic drug).
Cholinga cha JAK inhibitor ndi njira ya JAK yomwe ndi njira yowonetsera yomwe ili mkati mwa maselo omwe amachititsa kwambiri kutupa komwe kumayambitsa matenda a nyamakazi. Mwachindunji, JAKs (Janus kinases) ndi mavitamini amphamvu (ie, cytoplasmic protein tyrosine kinases) yomwe imafalitsa zizindikiro kuchokera kuzipatala zambiri za cytokine kupita kumtima wa maselo.
Pali ziwerengero zoposa 500 za "kinome" zaumunthu ndipo zimagawanika kukhala mabanja asanu ndi atatu. A JAK ali m'banja la tyrosine protein kinase-banja lomwe lili ndi mamembala 90. Banja la Janus likulumikiza (JAK) limaphatikizapo TYK2, JAK1, JAK2, ndi JAK3.
Akatswiri ofufuza atazindikira kuti udindo wa JAK umasewera mu chiwonetsero cha cytokine, iwo adakhala mbali yaikulu ya maphunziro a zachipatala. Tofacitinib inali yoyamba ya JAK inhibitor kuti ayesedwe kuchipatala ndikuvomerezedwa ku matenda a nyamakazi. Tofacitinib, yomwe imapangidwa ndi Pfizer, Inc., imalepheretsa JAK3 ndi JAK1, ndi JAK2 kumapeto. Tofacitinib sichikhudza TYK2.
Tofacitinib-Yoyamba YAK Inhibitor Yavomerezedwa ku Matenda a Chifuwa cha Matenda
Tofacitinib (dzina lakuti Xeljanz) inavomerezedwa monga mankhwala kwa akuluakulu moyenera - kudwala kwambiri nyamakazi ya nyamakazi yomwe inali ndi yankho lokwanira kapena losagwirizana ndi methotrexate .
Xeljanz ndi mankhwala opatsirana pakamwa, amapezeka ngati mapiritsi a 5 mg kuti azitengedwa kawiri tsiku ndi tsiku. Zingatengedwe kapena popanda chakudya. Palinso mlingo wa 11 mg kamodzi-tsiku uliwonse, wotchedwa Xeljanz-XR (kutulutsidwa kwowonjezera). Xeljanz ingatengedwe yokha (mwachitsanzo, yogwiritsidwa ntchito monga monotherapy), kapena ikhoza kuphatikizidwa ndi methotrexate kapena zina zomwe sizinali zachilengedwe. Xeljanz sayenera kugwiritsidwa ntchito ndi mankhwala osokoneza bongo.
Chitetezo cha JAK Inhibitor Mankhwala Osokoneza Bongo
Pofufuza za Xeljanz (tofacitinib), ofufuza anatsimikizira kuti zinali zofanana ndi mankhwala osokoneza bongo. Pali chiopsezo chowonjezereka cha matenda, zomwe zingakhale zovuta ndi matenda a chiwindi , komanso zomwe zingatheke kuti zikhale ndi neutropenia (msinkhu wa neutrophils, mtundu wa maselo oyera a magazi), hyperlipidemia (lipids zamtundu kapena mafuta m'magazi), ndi serum creatinine yokwera tofacitinib ntchito.
Chenjezo la Black Box linkafunika monga gawo la kuvomerezedwa ndi kulembedwa kwa tofacitinib kuti lichenjeze za zotsatirapo zoipa izi.
Baricitinib
Baricitinib anali wachiwiri JAK inhibitor kuti apereke NDA (New Drug Application) kwa FDA mu January 2016. A FDA apitiriza nthawi yowerengera kwa Baricitinib kuti athetse nthawi yowonjezera deta yowonjezera yoperekedwa ndi wogulitsa mankhwala, Lily ndi Incyte. Deta yowonjezerapo inaperekedwa poyankha pempho la FDA Information. Zowonjezera zowonjezereka zikuwoneka ngati kusintha kwakukulu kwa NDA yapachiyambi ndikuwonjezera miyezi itatu pa nthawi yowerengera.
Mu December 2016, Komiti ya European Medicines Agency ya Mankhwala Ogwiritsa Ntchito Mankhwala (CHMP) inalimbikitsa kupereka chithandizo ku European Union (EU) kwa Olumiant (baricitinib). Baricitinib inalimbikitsidwa kuti athe kuchiritsidwa ndi anthu akuluakulu omwe ali ndi matenda odwala matenda a nyamakazi omwe sali ovomerezeka, kapena omwe sangathe kulekerera mankhwala amodzi omwe amatsutsana ndi matendawa (DMARD).
Baricitinib ndi kamvekedwe kamodzi katsiku kameneka JAK1 / 2 inhibitor inasonyeza kuti amachiza matenda odwala nyamakazi. Dongosolo loyesera zachipatala lawonetsa kusintha kwakukulu kwa ululu, kutopa, thupi, komanso umoyo wokhudzana ndi thanzi labwino kwa odwala omwe sanayambe kuchiritsidwa ndi omwe adalephera mankhwala ena.
Mawu Ochokera
Pofuna kubwereza, JAK inhibitors amagawidwa ngati ma molekyulu a DMARD, osati mankhwala a biologic. Kusiyanitsa kwakukulu ndikuti JAK inhibitors amagwira ntchito mosavuta (mkati mwa maselo) ndi mankhwala a biologic ali ndi zolinga za extracellular (mwachitsanzo, mapulogalamu pamwamba pa maselo). Komanso, JAK inhibitors ndi mankhwala osokoneza bongo, pamene biologics imayambira kapena imayikidwa ndi kulowetsedwa.
Popeza anthu omwe ali ndi matenda a nyamakazi si onse omwe amachitapo kanthu pochiza chithandizo, nkofunika kuti apange ndikupanga njira zatsopano zothandizira. Kuwonjezera pa tofacitinib ndi baricitinib zomwe takambirana pamwambapa, mayesero a chipatala chachitatu akupitiriza kugwiritsa ntchito filgotinib ndi ABT-494-onse awiri omwe ali ndi kachilombo ka HIV.
> Zotsatira:
> Pakati pa Daniel E., MD. Zowona za Biologic Agents ndi Kinase Inhibitors mu Rheumatic Diseases. Zaposachedwa. Idasinthidwa pa February 2, 2017.
> McInnes, Iain B., PhD. Cytokine Networks mu Rheumatic Diseases: Zotsatira za mankhwala. Zaposachedwa. Idasinthidwa November 5, 2015.
> Nakayamada, S. et al. Kupita patsogolo kwa JAK Inhibitors kwa Chithandizo cha Matenda a Chifuwa. BioDrugs. October 2016.
> O'Shea, John J. et al. Janus Kinase Inhibitors mu Matenda Odzidzimutsa. Annals wa Rheumatic Diseases. April 2013.
> Elvidge, Suzanne. Dera la Deta la Delays pa Lilly ndi Incyte's Arthritis Mankhwala. BiopharmaDIVE. January 17, 2017.