Lalela Funda Kudivayisi kuphela Kwengeziwe Buka Kufakiwe Fasenra for Treatment of Eosinophilic Asthma

Ngo-November 2017, i-FDA ivume i-biologic Fasenra ukuphatha i-asthma ye-eosinophilic

Ngo-November 2017, i-FDA ivume i-biologic entsha yokwengeza ukwelashwa kwesifo se-asthma esiyinkimbinkimbi esiphambene nokuvuvukala kwe-eosinophilic (okungukuthi, i-asthma eosinophilic) ebizwa nge-benralizumab (Fasenra).

Ngokusho kwe-NIH, i-agent ye-biologic "yinto eyenziwe yenyama ephilayo noma imikhiqizo yayo futhi isetshenziselwa ukuvimbela, ukuxilongwa, noma ukwelashwa komdlavuza nezinye izifo.

Ama-biologic agents afaka ama-antibodies, ama-interleukin, nemithi yokugoma. "I-biologic agent ingabuye ibizwe ngokuthi i-agent ephilayo, izidakamizwa eziphilayo noma i-biologic.

Emhlabeni wonke, cishe abantu abayizigidi ezingu-315 bane-asthma. Kulaba bantu, amaphesenti angama-5 kuya kwangu-10 anesifo se-asthma esibi futhi, uma kufanelekile, angazuza ngokungenelela nge-biologic.

I-Fasenra Isebenza Kanjani?

Ukuze uqonde ukuthi uFasenra usebenza kanjani, kubalulekile ukuhlola ubuhlobo phakathi kwama-eosinophil, uhlobo lwe-white cell cell, ne-asthma. Ngokuvamile, ama-eosinophils asivikela ngokumelene nezibungu ezinamandla. Uma kusetshenziswe ngendlela engalungile, noma kunjalo, i-eosinophil ingalimaza izicubu futhi ibangele i-asthma. Ukukhiqizwa kwe-Eosinophil nomsebenzi kuthonywa i-cytokine okuthiwa i-interleukin-5 (i-IL-5).

I-Fasenra i-anti-monoclonal antibody esebenza ngokumelene nama-receptors e-IL-5 akhiwe kuma-eosinphils. Ku-athikili ka-2015 eyanyatheliswa ku- Current Medical Research and Opinion , i-Goldman kanye nabalobi ababambisene nabo babika lokhu okulandelayo: "UBenralizumab [Fasenra] inciphisa ngokuqondile, ngokushesha futhi kuphelile ukuqedwa kwama-eosinophil ngokusebenzisa i-cytotoxicity esondelene ne-antibody-dependent cell-mediated process, i-apoptotic we-eosinophil ekuqothulweni okubandakanya amangqamuzana ebulalayo wemvelo. "Ngokuyinhloko, uFasenra usebenzisana nokuqedwa kwama-eosinophils.

Amanye ama-antibodies a-monoclonal ngokumelene ne-IL-5-mepolizumab (i-Nucala) ne-reslizumab (Cinqair) -phawula i-IL-5 futhi ngaleyo ndlela adala ukunciphisa ama-eosinophil ngokusebenzisa izindlela ezingapheli nezingaqondile. Okubaluleke kakhulu, njengoFasenra, kokubili uNucala noCinqair banezela-ekwelapheni.

Isivivinyo se-Clinical ZONDA

Phakathi nesigaba se-Phase III ZONDA, abacwaningi base-AstraZeneca bahlola ukuthi ukuphathwa kwe-Fasenra kunganciphisa isidingo se-oral glucocorticoid therapy esetshenziselwa ukugcina ukulawula i-asthma kuziguli ezine-eosinophilia eziphikisanayo, noma ukwanda kwenani lama-eosinophil egazini.

Okubalulekile, ukwelashwa kwesikhathi eside nge-systemic, noma ngomlomo, i-glucocorticoids inemiphumela emibi eminingi engalungile echaphazela ama-musculoskeletal, endocrine, ama-cardiovascular, kanye nama-central central system. Abantu abasebenzisa i-glucocorticoids yomlomo isikhathi eside besikhathi sempilo banciphise ikhwalithi yokuphila. Ngeshwa, phakathi kwamaphesenti angama-32 no-45 abantu abane-asthma enamandla kakade bathatha i-glucocorticoids ne-dose ephezulu ehoxiswayo kanye ne-bronchodilators incike ekutheni njalo (ie, ukugcinwa) kwe-oral glucocorticoid therapy ukulawula i-asthma yabo.

Esigamekweni se-ZONDA, iziguli ezingu-369 zabhaliswe, kanti iziguli ezingama-220 zazingabalwa ngamaqembu amathathu. Phakathi nesilingo samaviki angu-28, iqembu lokuqala lokuhlola lithola izijovo ezingaphansi kweFasenra njalo emavikini amane, iqembu lesibili lokuhlola lathola izijovo ezingaphansi kweFasenra njalo emavikini ayisishiyagalombili, futhi iqembu lokulawula lathola ama-placebo injection. Ngaphezu kwalokho, abacwaningi banciphise amanani omlomo we-glucocorticoid athathwa yizo zonke amaqembu amathathu ezingeni eliphansi elidingekayo ukulawula i-asthma. Abacwaningi baphinde bahlola izinga lokukhuphuka kwesifo se-asthma, umsebenzi wamaphaphu, izimpawu, nokuphepha.

Nayi imiphumela yesilingo somtholampilo:

• Kuzo zombili amaqembu okuhlola athatha u-Fasenra, amanani okugcina omlomo womlomo we-glucocorticoid ayengamaphesenti angama-75 aphansi kunalawo asekuqaleni.

• Esikhathini seqembu le-placebo, umthamo wokugcina we-glucocorticoid womlomo wawungamaphesenti angu-25 aphansi kunalawo asekuqaleni.
• Abahlanganyeli abathatha uFasenra babevame ukwedlula izikhathi ezine ukuba banciphise umthamo we-glucocorticoid ngomlomo kunelabo abathola indawo yokuhlala.
• Esigabeni sokuhlola esithatha uFasenra njalo emasontweni amane, ukukhubazeka kwonyaka wonyaka wokukhuphuka kwesifo se-asthma kwehle ngamaphesenti angama-55 uma kuqhathaniswa neqembu elilawulayo.
• Emgomweni wokuhlola uthatha u-Fasenra njalo ngemva kwamasonto ayisishiyagalombili, ukukhubazeka kwonyaka okwenyuka kwamaphesenti angu-70 kuye kwawa ngamaphesenti angu-70 uma kuqhathaniswa neqembu elilawulayo.
• Umsebenzi we-Lung njengoba kulinganiswa usebenzisa ivolumu yokuphefumula okuphoqelelwe ngomzuzwana ongu-1 (FEV1) awufani neze nalabo abathatha u-Fasenra uma kuqhathaniswa nalabo abathatha indawo ye-placebo.

• Amaphesenti angamashumi ayisihlanu weziguli ezithola izilinganiso zokuqala ze-prednisone (okungukuthi, i-oral glucocorticoids), engaphansi noma elingana no-12.5 mg ngosuku, bakwazi ukuyeka ukusetshenziswa kwabo kwe-glucocorticoids ngomlomo ngenkathi bethatha uFasenra.
• Izinyathelo zokuhlola izinga lokuphila le-asthma elihlobene ne-asthma kulabo abathatha uFasenra uma kuqhathaniswa nalabo abathatha indawo ye-placebo bahlanganisiwe. Ezinye izinyathelo zabonisa ukuthuthukiswa kwezibonakaliso ze-asthma, kanti abanye abakhombisi ushintsho uma kuqhathaniswa nalabo abagulayo abathatha indawo ye-placebo.
• Izingosi zezenzakalo ezimbi zafana nalabo abathatha uFasenra nalabo abathatha indawo, okubonisa ukuthi kungenzeka ukuthi uFasenra uphephile.

Ngakho-ke, ukucasula kwe-asthma kubhekisela kuphi? Ngokusho kukaNair nozakwabo:

Ukukhushulwa kwesimo se-asthma kuchazwa ngokuthi ukuqhuma kwesifo sofuba okwenzeke okwesikhashana esenzweni se-systemic glucocorticoid okungenani izinsuku ezingu-3 ukuphatha izimpawu, ukuvakashelwa komnyango ophuthumayo okubangelwa yi-asthma eyabangela ukwelashwa nge-glucocorticoid ye-systemic ngaphezu kwesiguli imithi yesondlo ejwayelekile, noma esibhedlela esibhedlela ngenxa ye-asthma.

Phakathi nesilingo se-ZONDA, iziguli ezingu-166, noma amaphesenti angu-75, iziguli ezithatha u-Fasenra zathola okungenani umphumela owodwa oyingozi. Nansi ukuphazamiseka kwemiphumela emibi ebonwe ngesikhathi sokuhlolwa kwesilingo:

• I-Nasopharyngitis (amaphesenti angu-17)
• Ukuphulukisa isifo sofuba (amaphesenti angu-13)
• I-brronchitis (amaphesenti angu-10)

Inothi, i-nasopharyngitis ibhekisela ekuvukeni kwempumu nomoya ophezulu. Igama elivamile elibandayo libhekisela ku-nasopharyngitis. I-brronchitis ibhekisela ukuvuvukala kwe-airways engezansi, noma amashubhu e-bronchial emaphashini.

Ngokuphelele, iziguli ezingu-28 (amaphesenti angu-13) zathola ukuthi abacwaningi babheka yini imiphumela emibi "engathí sina" -ukuvame kakhulu ukuwohloka kwesifo se-asthma. Iziguli ezimbili kuphela ezithatha uFasenra zidinga ukuyeka lesi sidakamizwa. Lezi ziguli ezimbili zafa ngesikhathi sokuhlolwa kodwa izimbangela ezingahambisani nokuphathwa kwesiguli se-Fasenra-one zabulawa ukuhluleka kwenhliziyo kanti enye yafa nge-pneumonia. (Bobabili lezi ziguli zinezinye izifo eziningi, noma izidakamizwa.)

Abacwaningi baphetha ngokuthi kubantu abane-asthma eosiniphilic enkulu, umthamo wesondlo we-oral glucocorticoid therapy ungancishiswa kulabo abathola uFasenra njalo emavikini ayisishiyagalombili. Okubalulekile, ekuhlolweni kwe-ZONDA, abacwaningi bathola ukuthi ukukhubazeka kwonyaka waminyaka yonke okwenziwe yi-asthma kuncane kakhulu kubantu abathatha u-Fasenra njalo ngemva kwamasonto ayisishiyagalombili uma kuqhathaniswa nalabo abaphuza imithi njalo emasontweni amane.

Izivivinyo ezengeziwe zomtholampilo

Eminye imilingo emibili yokwelapha ebizwa ngokuthi uSIROCCO noCALIMA, abacwaningi baphinde bahlola ukusebenza koFasenra. Kulezi zivivinyo, ezanyatheliswa ezinyangeni ezimbalwa ngaphambi kwemiphumela yecwaningo lweZONDA, abacwaningi bathole ukuthi izijovo ezingaphansi kweFasenra njalo emasontweni amane noma ayisishiyagalombili zanciphisa ukukhushulwa kwe-asthma, umsebenzi ophuthumayo wamaphaphu (okungukuthi, ukwandisa amanani we-FEV1), ukulawulwa kwezimpawu ezithuthukisiwe, kanye i-blood eosinophils egazini egazini ezigulini ezinezibalo ezingaphezu kuka-300 amaseli / microliter. Ngaphezu kwalokho, abacwaningi bathola ukuthi-nakuba ukuhlolwa kwezibalo kungalinganiselwa-ukuhlolwa kwe-Fasenra njalo ngemva kwamasonto ayisishiyagalombili kubonakala sengathi kuphumelela kakhulu kunokulawula umuthi njalo ngemva kwamasonto amane. Okubaluleke kakhulu, ukuphatha lesi sidakamizwa njalo ngemva kwamasonto ayisishiyagalombili kunciphise umthwalo wemithi kumguli.

Kuyathakazelisa ukuthi ngesikhathi kuhlolwa i-ZONDA, iziguli ezingu-20 ezithatha u-Fasenra azizange zithole ukuncipha kwamanani we-glucocorticoid ngomlomo nakuba ukuhlolwa kwe-eosinophil yeziguli kwakufana nalabo ababencishiswe kakhulu emithonjeni yabo yokugcina ye-glucocorticoid. I-Nair kanye nozakwethu baxosha ukuthi "mhlawumbe ukutholakala kwegazi eosinophilia kungase kungabonakali i-eosinophil njengesisindo esiyinhloko esihlokweni kwezinye iziguli."

Phakathi nokuhlolwa kwe-SIROCCO ne-CALIMA, i-Goldman nabacwaningi bahlola ukuthi ngabe uFasenra anganciphisa amazinga okukhuphuka kwesimo se-asthma kuziguli kungakhathaliseki ukuthi yi-eosinophil counts. Abacwaningi bathola ukuthi kubantu abane-eosinophil ababalwa-ababala kunenani noma elilingana namaseli angu-150 / microliter-Fasenra "kuncishisa umthwalo wezifo kanye nezindleko zokunakekelwa kwezempilo kulezi zinkinga ezinzima zokwelapha ezingakhetha ukwelashwa okulinganiselwe."

Ngokufanayo, izilingo zangaphambili zemithi zibonise ukuthi amanye ama-antibodies amabili e-IL-5 okwamanje emakethe, i-Nucala neCinqair, ayasebenza ezigulini ezinenani eliphansi le-eosinophil egazini (okungukuthi, elikhulu noma elingana namaseli angu-150 / microliter) .

Ngokuvamile, izinga legolide lokuxilongwa kwe-asthma ye-eosinophilic lihilela ukuboniswa kokuvuvukala emoyeni we-airson we-bronchial ngokusekelwe ekuhlolweni kwe-biopsy noma i-sputum engenayo. Lezi zinqubo, kunzima ukwenza futhi zidinga ukuqeqeshwa okukhethekile; ngakho-ke, abaqashiwe njalo. Esikhundleni salokho, odokotela bancike ekubalweni kwe-eosinophil yegazi, okuyinto noma ukubikezela kokuqina kwesifuba, akuphelele. Ngaphezu kwalokho, ama-eosinophil ahluke kakhulu ngokuya ngesikhathi futhi azwela nokuphathwa kwe-corticosteroid.

Ngokusho kukaGoldman nabalobi ababambisene nabo:

Imiphumela yokuhlaziywa kwamanje igcizelela ukulinganiselwa okusemandleni okuchaza abaphendulayo abangaba khona ekuthatheni ukwelashwa kwe-eosinophil, ngokusekelwe e-blood eosinophil count of [300 cells / microliter] yedwa. Ukulinganisa okuningiliziwe kwe-phenotype eosinophilic ngaphandle kwe-blood eosinophil ukubalwa kuyadingeka okusebenzisa ukuhlanganiswa kwezici zomtholampilo (isb., I-poop polyposis), kanye nokubala kwe-eosinophil yegazi. Ukubala kwe-eosinophil yegazi kufanele kulinganiswe ngamaphoyinti amaningana wesikhathi ukuxazulula izinkinga zokuhlukahluka ezingabangela ukuxilongwa okulahlekile kwalabagulayo abane-eosinophilic inflammation.

Fasenra vs. Umncintiswano

Njengamanje, akucaci ukuthi uFasenra ubambe kanjani ngokumelene nezinye izinto eziphilayo ezikhomba IL-5: Nucala noCinqair. Ku-athikili ethi "Benralizumab yokwelapha isifo se-asthma," uSobo kanye nabalobi abambisene nabo babhala ukuthi kungenzeka ukuthi uFasenra udinga ukuphindwa kaningi kuneNucala noCinqair. Nokho, abacwaningi babhala lokhu okulandelayo mayelana nokuqhathaniswa kwezidakamizwa ezintathu:

Okunye ukuthuthukiswa kwezibalo zesifo se-asthma kanye nekhwalithi yokuphila kubonakala kuzo zonke izinto eziphilayo ezintathu, kepha ukuphikisana komtholampilo kwalezi zithuthukisa akucaci kahle. ... Kuze kube yilapho izinga elilawulwa ngokungahleliwe ngokulinganayo liqhathanisa ngokucacile lezi ezintathu, ukukhetha phakathi kwabo ukwelashwa kwe-asthma ye-eosinophilic kunzima.

U-AstraZeneca, owenza u-Fasenra, uhlela ukuthenga intengo ephansi kuneNucala noCinqair, enye eyongezwayo nge-IL-5 biologics okwamanje emakethe. Nakuba izintengo zezidakamizwa ziyahlukahluka ngezici eziningana, ngokwezinye izilinganiso, iNucala ibiza cishe ngama-$ 32,500 ngonyaka, kanti i-Cinqair ibiza cishe. Okokugcina, ngoba i-Fasenra ingasetshenziswa ngokuphindaphindiwe kunamanye ama-biologics, intengo izoba yancipha.

> Imithombo:

> Goldman M et al. Ukuhlangana phakathi kwegazi le-eosinophil count kanye ne-benralizumab ukuphumelela kweziguli ezine-asthma ezinzima ezingalawuleki: ama-subanalyses eSigaba III SIROCCO noCALIMA. Ucwaningo Lwezokwelapha Namanje . 2017; 33: 1605-1613. https://doi.org/10.1080/03007995.2017.1347091.

> Nair P et al. I-Oral Glucocorticoid-Ukwehliswa Kwe-Benralizumab E-Asthma Enamandla. I-New England Journal of Medicine . 2017; 376: 2448-58. https://doi.org/10.1056/NEJMoa1703501.

> Saco TV et al. Benralizumab yokwelashwa kwesifo se-asthma. Ukubuyekezwa kobuchwepheshe be-Pharmacology Clinic. Ukubuyekezwa kochwepheshe we-Immunology Clinic . 2017; 13 (5): 405-413. http://www.tandfonline.com/doi/full/10.1080/1744666X.2017.1316194.

> Wardlaw AJ. Ama-Eosinophils nezinkinga ezihlobene. Ku: Kaushansky K, Lichtman MA, Prchal JT, Levi MM, Press OW, Burns LJ, Caligiuri M. eds. Williams Hematology, 9e eNew York, NY: McGraw-Hill