Ua hoʻolaha ʻo AbbVie i kēia lā i nā hopena kiʻekiʻe loa mai U-EXCEL, kahi haʻawina induction Phase 3, e hōʻike ana i ka upadacitinib (45 mg hoʻokahi i kēlā me kēia lā) i loaʻa i nā helu hope ʻelua o ka remissiona clinical, b a me ka pane endoscopic i ka pule 12.1 U-EXCEL ka lua o ʻelua Nā haʻawina hoʻokomo ʻana o ka Phase 3 e loiloi i ka palekana a me ka maikaʻi o ka upadacitinib i nā poʻe mākua me ka maʻi maʻamau a i ʻole koʻikoʻi o ka maʻi o Crohn i loaʻa ʻole ka pane kūpono ʻole a i ʻole ka hoʻomanawanui ʻana i ka lāʻau maʻamau a i ʻole ka lāʻau olaola.1
ʻO U-EXCEL ka mea like me ka U-EXCEED, me ke kala kala ʻana i ana ʻia e ka Crohn's Disease Activity Index (CDAI) a me nā hōʻailona i hōʻike ʻia e ka mea maʻi o ka ʻeha o ka ʻōpū/ʻeha ʻōpū (SF/AP).1 A ʻoi aku ka nui o ka nui o nā maʻi i mālama ʻia me ka regimen induction 12-week o upadacitinib 45 mg i kēlā me kēia lā i loaʻa i ke kala kala ma CDAI i ka pule 12 i hoʻohālikelike ʻia me kahi placebo (49 pakeneka versus 29 pakeneka; p<0.0001). SF/AP (1 pakeneka o ka upadacitinib-treated maʻi versus 51 pakeneka i placebo-treated maʻi; p<22) .0.0001 I ka pule 1, he nui ka hapa nui o nā maʻi i mālamaʻia me ka upadacitinib 12 mg i loaʻa i ka pane endoscopic i hoʻohālikelikeʻia i ka hui placebo ( 45 pakeneka me ka 46 pakeneka, p<13).0.0001
E like me nā hopena mai ka U-EXCEED induction study, ʻoi aku ka kiʻekiʻe o ka nui o nā maʻi e loaʻa ana i ka upadacitinib 45 mg i loaʻa pū i ke kala ʻana i ka steroid-free clinical remissioned no CDAI a me ka SF / AP i hoʻohālikelike ʻia me kahi placebo i ka pule 12 ma waena o nā poʻe maʻi e lawe ana i nā corticosteroids ma baseline.1 Early ʻO ka hoʻomaikaʻi ʻana o ka hōʻailona i ana ʻia e CR-100 (i wehewehe ʻia e like me ka hoʻemi ʻana o CDAI ≥100 mau helu mai ka papa kuhikuhi) i ka pule ʻelua a me ke kala ʻana i ka lāʻau lapaʻau i ka pule ʻehā ua loaʻa pū kekahi e ka hapa nui o nā maʻi e loaʻa ana i ka upadacitinib 45 mg.1
I loko o ka 12-week, double-blind, placebo-controlled period, ua kūlike ka ʻike palekana o upadacitinib 45 mg me ka ʻike palekana i ʻike ʻia ma nā haʻawina mua ma nā hōʻailona, me ka ʻike ʻole ʻia o nā pilikia palekana hou. a me ka anemia ma ka hui upadacitinib 1 mg.45 Ua loaʻa nā hanana ʻino koʻikoʻi i ka 1 pakeneka o nā maʻi i ka hui upadacitinib 6.9 mg i hoʻohālikelike ʻia me 45 pakeneka o nā maʻi i ka hui placebo. mg a me 6.8 pakeneka i loko o ka poe i loaa placebo.1 Herpes zoster ua hōʻike 'ia i loko o 1.1 pakeneka o ka poe maʻi lapaʻauʻia me upadacitinib 45 mg, nā hihia a pau nonserious.1.7 Aohe hihia o ka ho'okolokolo 'ana i ka gastrointestinal perforation a make paha i loko o ka placebo-controlled period.1 Ua hōʻike ʻia kekahi hihia o ka hanana cardiovascular nui (MACE) i ka hui placebo.2.9
ʻO nā maʻi i loaʻa i ka upadacitinib 45 mg a ʻaʻole i hoʻokō i ka pane lapaʻau i ka pule 12 ua hoʻokomo ʻia i loko o kahi hui lapaʻau 12-wiki hou me ka upadacitinib 30 mg.1 Ma kēia pūʻulu, ua make kekahi maʻi i ka COVID-19.1 ʻO nā maʻi ma kahi placebo a ua hana. ʻaʻole i loaʻa ka pane lapaʻau i ka pule 12 i hoʻokomo ʻia i loko o kahi cohort lapaʻau 12-week me upadacitinib 45 mg.1 Ma waena o kēia mau maʻi, aia hoʻokahi hihia o ka hoʻopaʻapaʻa ʻana i ka gastrointestinal perforation.1
Ma U-EXCEL, ʻaʻole i hōʻike ʻia i nā maʻi ma luna o ka lāʻau upadacitinib i hōʻike ʻia i nā maʻi i hoʻopaʻa ʻia i ka MACE, malignancy a i ʻole ka hanana venous thromboembolic.
E hōʻike ʻia nā hualoaʻa piha mai ka noiʻi U-EXCEL ma nā ʻaha kūkā lapaʻau e hiki mai ana a paʻi ʻia i loko o kahi puke moʻolelo lapaʻau i loiloi ʻia e nā hoa. Ua hoʻolaha ʻia nā hopena kiʻekiʻe mai ka māhele 3 o ka haʻawina induction mua, ʻo U-EXCEED, ma Dekemaba 2021 a ke hoʻomau nei ka noiʻi mālama ʻana no nā mea ʻelua. ʻAʻole ʻae ʻia ka hoʻohana ʻana i ka upadacitinib i ka maʻi o Crohn a ʻaʻole i loiloi ʻia kona palekana a me ka pono e nā luna hoʻoponopono.
Ua wehewehe ʻia ke kala ʻana o ka maʻi maʻi me ka ʻole o ka steroid (no ka CDAI <150, a i ʻole ka SF/AP me ka awelika o kēlā me kēia lā SF ≤2.8 a ʻaʻole i ʻoi aku ka hewa ma mua o ka helu helu AP ≤1 a ʻaʻole i ʻoi aku ka hewa ma mua o ka helu kumu) i waena o nā poʻe maʻi e lawe ana i nā corticosteroids ma ke kumu.
He aha e lawe ʻia mai kēia ʻatikala:
- Consistent with results from the U-EXCEED induction study, a significantly higher proportion of patients receiving upadacitinib 45 mg also achieved steroid-free clinical remissiond per CDAI and per SF/AP compared to placebo at week 12 among patients taking corticosteroids at baseline.
- 1 A significantly greater proportion of patients treated with a 12-week induction regimen of upadacitinib 45 mg daily achieved clinical remission per CDAI at week 12 compared to placebo (49 percent versus 29 percent.
- 1 Early symptom improvement measured by CR-100 (defined as reduction of CDAI ≥100 points from baseline) at week two as well as clinical remission at week four were also achieved by a significantly higher proportion of patients receiving upadacitinib 45 mg.
