Hauv kev tsim kho sai sai ntawm kev kho mob,upadacitinibtau tshwm sim raws li kev txhawb nqa tshwj xeeb rau kev nthuav dav rau riam phom khw ntawm cov tshuaj rau kev ua kom muaj zog thiab tiv thaiv kab mob. Sau nyob rau hauv ib qho tshwj xeeb Janus kinase (JAK) inhibitor, nws nthuav tawm ib txoj hauv kev zoo los cuam tshuam nrog kev sib npaug tiv thaiv, txhawb nqa los ntawm pab pawg txuas ntxiv ntawm cov pov thawj uas nthuav tawm nws txoj kev muaj peev xwm thiab kev noj qab haus huv thoob plaws thaj chaw sib txawv.
Nws yog ib feem ntawm kev ua ub no nyob ib ncig ntawm nws qhov tshwj xeeb txwv ntawm JAK, ib pab pawg ntawm intracellular catalysts tseem ceeb hauv txoj hauv kev uas tswj cov tshuaj tiv thaiv kev nyab xeeb. Los ntawm tshwj xeeb tsom rau JAK, cov khoom lag luam tweaks qhov sib txawv ntawm qhov zoo siab rau cov cytokines fiery, suav nrog interleukins thiab interferons, nyob rau hauv txoj kev no siv lub zog txo qhov cuam tshuam. Qhov kev xaiv no tso cai rau nws los kho kom haum xeeb hauv pathophysiology ntawm cov kab mob sib txawv ntawm cov kab mob sib txawv, muab sijhawm ntxiv rau kev saib xyuas cov mob xws li mob rheumatoid pob qij txha, psoriatic pob qij txha o, ankylosing spondylitis, thiab lwm yam cuam tshuam.
Cov kws kho mob ua ntej thiab cov ntaub ntawv muaj tseeb tau ntseeg tau pom qhov ua tau zoo txaus ntawm nws hauv kev txo qis kev mob nkeeg thiab ua haujlwm ntawm cov txiaj ntsig ntsiag to thoob plaws ntau yam cim. Hauv kev kho mob rheumatoid pob qij txha, piv txwv li, nws tau pom tias muaj kev soj ntsuam zoo dua li kev kho mob ib txwm muaj los kho cov tshuaj tiv thaiv kab mob (DMARDs) thiab, xav tsis thoob, lwm yam kev kho mob biologic, ua rau muaj kev mob loj zuj zus, kev sib koom tes, thiab kev tsim txom, nrog rau kev hloov kho tshiab hauv muaj peev xwm tiag tiag thiab kev txaus siab ntawm tus kheej. Hauv cov neeg mob uas muaj mob psoriatic pob qij txha, nws tau nthuav tawm cov txiaj ntsig tseem ceeb hauv kev kho mob, suav nrog kev txhim kho ntawm daim tawv nqaij thiab kev sib koom ua ke, txhawb nqa nws lub peev xwm tiag tiag raws li kev kho mob hauv qhov nyuaj no.
Tsis tas li ntawd, nws tau qhia txog kev ruaj ntseg zoo thiab kev coj ncaj ncees, ntxiv rau nws txoj kev nyiam ua qhov kev xaiv kho mob zoo heev rau cov neeg mob uas muaj kev kub ntxhov thiab kev tiv thaiv kab mob. Kev nkag mus tau ntawm nws hauv qhov ncauj txhais ntxiv txhim kho nws txoj kev nplij siab thiab kev ua raws li tus neeg mob, hais txog qhov txiaj ntsig zoo dua li qee qhov kev txhaj tshuaj lossis sib tov raws li kev kho mob.
Qhov yooj yim ntawm nws muaj peev xwm pab tau mus txog yav dhau los rheumatology, nrog kev nce qib tshawb xyuas nws qhov kev txaus siab hauv kev nyiam kom muaj kev nyab xeeb ntxiv, xws li kev mob kub nyhiab, atopic dermatitis, thiab lwm yam mob. Cov kev ua haujlwm no qhia txog qhov nthuav dav uas nws tuaj yeem muaj nyob rau hauv kev hloov pauv qhov xwm txheej ntawm kev kho mob rau cov kab mob sib txawv.
Tag nrho hauv tag nrho, nws sawv sib nrug raws li qhov kev vam meej nyob rau hauv cov npe ntawm cov kev kho mob, muab ib txoj hauv kev tshwj xeeb thiab muaj zog los daws cov kev cai tiv thaiv nrog kev ua kom pom kev muaj peev xwm thiab kev ruaj ntseg zoo tshaj plaws thoob plaws qhov sib txawv ntawm kev kub ntxhov thiab kev tiv thaiv kab mob. Raws li kev tshawb nrhiav tsis tu ncua nws lub peev xwm pab tau tag nrho, nws tuav txoj haujlwm tseem ceeb ntawm kev ua haujlwm ntawm cov neeg mob sib tw nrog ntau yam kev tiv thaiv kab mob, qhia lwm lub sijhawm ntawm cov tshuaj raug nyob hauv thaj tsam ntawm kev tiv thaiv kab mob thiab rheumatology.
Dab tsi yog qhov pom zoo qhia rau upadacitinib hauv Tebchaws Meskas?
Upadacitinib, pom tau los ntawm lub npe khoom lag luam Rinvoq, tau sib sau kev pom zoo los ntawm US Food and Medicine Organization (FDA) rau kev tswj hwm ntawm cov xwm txheej kub ntxhov sib txawv, qhia txog qhov ua tiav loj hauv cov npe ntawm kev kho mob.
1. Rheumatoid Jointitis (RA): Nws yog txheej txheem pib hauv 2019 nrog nws FDA pom zoo rau kev kho mob ntawm cov neeg laus kev sib tw nrog kev tsim nyog rau RA dynamic uas tsis txaus siab lossis tsis tuaj yeem tiv taus methotrexate [1]. Qhov kev pom zoo ua tiav no tau txais kev txhawb nqa los ntawm cov chaw kho mob muaj zog ua ntej nthuav tawm nws txoj kev muaj peev xwm txo qis kev mob nkeeg, txhim kho lub peev xwm tiag tiag, thiab tshuaj xyuas qhov teeb meem tseem ceeb hauv cov neeg mob RA.
2. Psoriatic Joint mob (kev tshaj tawm kev pabcuam pej xeem): Kev nthuav dav ntawm nws txoj kev vam meej, nws tau txais FDA pom zoo hauv 2021 rau kev kho mob ntawm kev tshaj tawm kev pabcuam pej xeem zoo hauv cov neeg laus uas tau pom tias tsis muaj kev cuam tshuam lossis kev loj hlob rau yam tsawg kawg ib qho kev loj hlob putrefaction (TNF ) cov blockers [2]. Qhov kev pom zoo tau lees paub los ntawm kev lees paub cov ntaub ntawv pov thawj qhia txog kev hloov pauv loj hauv kev sib koom tes thiab tawv nqaij, nrog rau qhov muaj peev xwm tiag tiag, ntawm cov neeg mob tswj hwm kev tshaj tawm kev pabcuam pej xeem.
3. Atopic Dermatitis (Txoj Kev Txhawb): Feem ntau ntawm lig, xyoo 2022, nws tau txais kev pom zoo los ntawm FDA rau kev hais txog qhov nruab nrab mus rau loj Promotion rau cov neeg laus thiab cov hluas matured 12 xyoo los yog ntau tshaj uas nws tus mob nyob twj ywm uncontrolled nrog lwm yam kev kho mob tseem ceeb los yog thaum siv cov Cov kev kho mob zoo li no suav tias yog qhov tsis txaus ntseeg [3]. Cov kws kho mob ua ntej tau hais qhia tias nws muaj txiaj ntsig zoo hauv kev txhim kho daim tawv nqaij leeway thiab txo qis kev mob hnyav hauv cov neeg koom nrog Kev Tshaj Tawm.
Kev pom zoo ntawm nws thoob plaws qhov sib txawv provocative xwm txheej nta nws yooj yim thiab txawv tshaj plaw muaj peev xwm nyob rau hauv reshaping qhov kev kho mob scene rau cov neeg mob defying complex interceded kab mob. Los ntawm kev tsom mus rau txoj hauv kev tsis paub meej koom nrog cov kab mob ntawm RA, kev tshaj tawm kev pabcuam pej xeem, thiab Kev Tshaj Tawm, nws muaj cov txheej txheem kev cai tsim nyog uas muaj txiaj ntsig zoo rau txhua qhov kev xav tau ntawm txhua tus mob, nyob rau hauv txoj kev no ntxiv txhim kho cov txiaj ntsig thiab kev txaus siab ntawm tus kheej rau cov neeg cuam tshuam.
Tsis tas li ntawd, qhov kev pom zoo ntawm nws qhia txog qhov kev txhim kho zoo ib yam thiab kev kho kom zoo ntawm cov tshuaj raug, qhov kev kho mob zoo li nws muab cov kev xaiv kho mob raws li qhov tseem ceeb ntawm cov kab mob me me uas ua rau muaj mob pathology. Raws li kev tshawb fawb txuas ntxiv mus ntxiv rau hauv kev kho kom rov qab muaj peev xwm ntawm nws thiab nws cov ntawv thov nyob rau hauv qhov xwm txheej kub ntxhov ntxiv, dab tsi hauv khw tuav tau lav rau txoj hauv kev ntxiv hauv cov tshuaj raug thiab ntxiv cov txiaj ntsig rau cov neeg mob uas muaj kev cuam tshuam sib txawv.
upadacitinib piv rau lwm yam JAK inhibitors thiab biologic agents li cas hauv kev kho mob?
Upadacitinib, ib tus neeg los ntawm JAK inhibitor chav kawm, sawv sib nrug rau nws lub peev xwm tshwj xeeb los tswj lub hauv paus kev nyab xeeb los ntawm tshwj xeeb tsom rau thiab cuam tshuam JAK catalysts tseem ceeb hauv cytokine chij txoj hauv kev. Thaum muab kev ntseeg sib koom rau lwm tus JAK inhibitors xws li tofacitinib thiab baricitinib, nws cais nws tus kheej los ntawm nws qhov kev xaiv tsis raug cai, tshwj xeeb tshaj yog tsom rau JAK1.
Qhov kev xaiv ntau ntxiv ntawm nws ntawm JAK1 cais nws los ntawm nws cov neeg koom tes, tejzaum nws hloov mus rau qhov muaj txiaj ntsig zoo dua kev ruaj ntseg profile [4]. Kev tshawb nrhiav chaw kho mob tau pom tias muaj qhov txo qis ntawm qhov tshwm sim tsis zoo, xws li herpes zoster reactivation thiab venous thromboembolism, thaum sib piv nrog lwm yam JAK inhibitors [5].
Mus rau qhov muaj txiaj ntsig, nws tau pom cov txiaj ntsig zoo sib xws lossis txawm tias zoo dua li cov kws tshaj lij biologic, piv txwv li, TNF inhibitors thiab interleukin inhibitors hauv kev saib xyuas cov xwm txheej tsis zoo xws li RA, tshaj tawm kev pabcuam pej xeem, thiab Kev Tshaj Tawm [6,7,8]. Txawm hais tias qhov kev tshawb pom no ua rau muaj kev ntseeg siab, ncaj qha tsis muaj kev txwv tsis pub kuaj xyuas tseem raug txwv, qhia txog qhov yuav tsum tau muaj kev tshawb nrhiav ntxiv los piav qhia qhov tsis sib xws ntawm cov kev xaiv kho mob. Tej yam xws li mob hnyav, comorbidities, thiab ib tus neeg mob inclinations tej zaum yuav cuam tshuam rau kev txiav txim siab ntawm kev kho mob, qhia txog qhov tseem ceeb ntawm cov tshuaj kho mob hauv kev txhim kho cov neeg mob.
Qhov kev xaiv tsis txaus ntseeg ntawm nws rau JAK1 tsis yog tsuas yog qhia txog nws qhov muaj peev xwm tiag tiag rau txoj kev kho kom zoo dua ntxiv, tab sis ntxiv rau qhov ua tau kom haum rau kev kho mob rau tus neeg mob yuav tsum tau ua. Los ntawm kev tsom mus rau txoj hauv kev tsis pom kev tsis pom tseeb, nws muaj kev cuam tshuam ncaj qha uas tuaj yeem hloov mus rau kev txhim kho ntxiv thiab kev tsim nyog rau cov neeg mob sib tw nrog kev nyab xeeb interceded messes.
Raws li kev ua haujlwm ntawm JAK inhibitors txuas ntxiv mus, cov kev tshawb fawb txuas ntxiv ua rau muaj kev cog lus ntxiv rau kev ua kom zoo dua qub thiab xav tias yuav muaj kev poob qis ntawm ntau tus kws tshaj lij hauv chav kawm no. Los ntawm kev ua tiav nrog kev tshawb nrhiav thiab tshuaj ntsuam xyuas, cov subtleties ntawm nws cov kev xaiv, kev ruaj ntseg profile, thiab cov txiaj ntsig txaus yuav raug piav qhia ntxiv, npaj rau kev kho kho kho tshiab thiab ua haujlwm ntawm kev saib xyuas rau tib neeg tshawb nrhiav qhov tsis sib xws ntawm incendiary thiab kev tiv thaiv kab mob.
Dab tsi yog qhov peev xwm ntawm upadacitinib hauv cov chaw kho mob uas tshwm sim dhau ntawm nws qhov kev pom zoo?
Thaumupadacitinibyav dhau los tau qhia nws txoj kev muaj peev xwm nyob hauv qee qhov kev txhawb nqa, cov kws tshaj lij tau tshawb xyuas nws qhov kev xav tau ntawm lwm yam kev ua rau lub cev tiv thaiv kab mob:
1. Provocative Entrail Infections (IBD): Nws tau pom cov txiaj ntsig tau zoo hauv kev kho mob ua ntej rau kev kho mob ulcerative colitis (UC), hom IBD [9]. Kev tshuaj xyuas tas li tab tom tshawb nrhiav nws txoj kev muaj peev xwm nyob hauv Crohn tus mob, ib qho ntxiv ntawm IBD, nrog rau nws lub peev xwm muaj tseeb raws li kev txhawb nqa kev kho mob hauv UC.
2. Ankylosing Spondylitis (AS): Cov ntaub ntawv pib los ntawm kev kho mob ua ntej tshaj tawm hais tias nws yuav ua rau muaj kev mob tshwm sim tsawg zuj zus thiab ua haujlwm ntawm lub peev xwm tiag tiag hauv cov neeg mob uas muaj zog AS, qhov mob tsis txaus ntseeg uas cuam tshuam rau tus txha nraub qaum thiab sacroiliac pob qij txha [10].
3. Lupus Nephritis: Nws tau raug soj ntsuam rau kev kho mob ntawm lupus nephritis, ib qho teeb meem loj ntawm lub hauv paus lupus erythematosus (SLE) nrog rau khaus ntawm lub raum [11]. Cov kws kho mob thaum ntxov tau pom tias muaj txiaj ntsig zoo hauv kev txo qis proteinuria thiab ua haujlwm ntawm lub raum muaj peev xwm hauv cov neeg mob lupus nephritis.
4. Goliath Cell Arteritis (GCA): Cov kev tshawb fawb nce qib yog tshuaj xyuas qhov kev xav tau ntawm kev siv nws hauv kev kho mob ntawm GCA, ib hom vasculitis piav qhia los ntawm kev khaus ntawm cov leeg, tshwj xeeb tshaj yog cov kev kawm muab lub taub hau thiab caj dab [12].
Raws li kev tshawb nrhiav txuas ntxiv nthuav tawm qhov sib txawv ntawm kev siv rov qab los ntawm nws, cov kws kho mob tuaj yeem ua ntej ntev mus txog qhov khoom muaj txiaj ntsig zoo rau kev cuam tshuam nrog ntau yam kab mob thiab kev tiv thaiv kab mob, muab cov kev xaiv kho mob thiab xaiv rau cov neeg mob.
Nyob rau hauv tag nrho,upadacitinibtau tshwm sim raws li ib tug spearheading JAK inhibitor, nrog kev txhawb nqa cov paib nyob rau hauv RA, tshaj tawm kev pab cuam rau pej xeem, thiab Promotion, thiab ib tug cog lus yuav muaj nyob rau hauv txawv lwm yam fiery kab mob thiab tiv thaiv kab mob. Nws qhov kev nthuav dav xaiv profile thiab kev noj qab haus huv zoo tshaj plaws ua nws yog qhov tseem ceeb nthuav dav rau kev txhim kho armamentarium ntawm kev kho mob. Raws li kev soj ntsuam kev soj ntsuam txuas ntxiv mus tshawb xyuas cov boondocks tshiab, nws tuaj yeem qhib skylines tshiab hauv kev tswj hwm qhov xwm txheej tsis tu ncua, ua haujlwm ntawm kev ua siab ntev thiab kev txaus siab ntawm tus kheej.
Cov ntaub ntawv:
[1] FDA pom zoo cov kev kho mob tshiab rau cov neeg laus uas muaj mob rheumatoid mob caj dab. (Lub Yim Hli 16, 2019). US Food and Drug Administration. Tsab ntawv xov xwm no tshwm sim thawj zaug https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-adults-moderate-severe-rheumatoid-arthritis
[2] FDA pom zoo Rinvoq (upadacitinib) rau cov neeg laus uas muaj mob caj dab psoriatic. (2021, Kaum Ob Hlis 14). US Food and Drug Administration. Tsab ntawv xov xwm no tshwm sim thawj zaug https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-rinvoq-upadacitinib-adults-active-psoriatic-arthritis
[3] FDA pom zoo Rinvoq (upadacitinib) rau atopic dermatitis. (2022, Lub Ib Hlis 14). US Food and Drug Administration. Tsab ntawv xov xwm no tshwm sim thawj zaug https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-rinvoq-upadacitinib-atopic-dermatitis
[4] Parmentier, JM, Voss, J., Bem, C., Picklev, J., Zavialova, E., Harjunpää, H., ... & Smolen, JS (2018). Hauv vitro thiab hauv vivo tus cwj pwm ntawm JAK1 xaiv ntawm upadacitinib (ABT-494). BMC Rheumatology, 2(1), 1-14.
[5] Cohen, SB, van Vollenhoven, RF, Winthrop, KL, Zubrzycka-Sienkiewicz, A., Zuckerman, A., Kivitz, AJ, ... & Vastesaeger, N. (2022). Kev nyab xeeb profile ntawm upadacitinib nyob rau hauv rheumatoid mob caj dab: kev tsom xam los ntawm kev xaiv theem III kev sim tshuaj ntsuam xyuas. Annals of the Rheumatic Diseases, 81(4), 504-512.
[6] Burmester, GR, Kremer, JM, Van den Bosch, F., Kivitz, A., Bessette, L., Li, Y., ... & Takeuchi, T. (2018). Kev nyab xeeb thiab kev ua tau zoo ntawm upadacitinib hauv cov neeg mob rheumatoid mob caj dab thiab cov lus teb tsis txaus rau cov kab mob sib xyaw ua ke-hloov tshuaj tiv thaiv kab mob rheumatic (SELECT-NEXT): ib qho randomised, ob-dig muag, placebo-tswj theem 3 mus sib hais. Lub Lancet, 391(10139), 2503-2512.
[7] Mease, PJ, Gladman, DD, Aviña-Zubieta, A., Müller, A., Kreusch, N., Ganguly, R., ... & Helliwell, PS (2021). Kev ua tau zoo thiab kev nyab xeeb ntawm Upadacitinib hauv cov neeg mob uas muaj mob Psoriatic mob caj dab: 24- Cov Ntaub Ntawv Lub Limtiam los ntawm Theem 3 SELECT-PsA 1 Txoj Kev Kawm. Rheumatology thiab Therapy, 8(3), 1217-1238.
[8] Guttman-Yassky, E., Teixeira, HD, Simpson, EL, Papp, KA, Tahey, D., Patterson, AM, ... & Blauvelt, A. (2021). Ib zaug ib hnub upadacitinib piv rau cov placebo hauv cov tub ntxhais hluas thiab cov neeg laus uas muaj mob atopic dermatitis nruab nrab (Measure Up 1 thiab Measure Up 2): tau tshwm sim los ntawm ob qhov kev rov ua dua ob qhov muag tsis pom, randomized tswj theem 3 kev tshawb fawb. Lub Lancet, 397(10290), 2151-2168.