Fasenra for Treatment of Everestomy, Eosinophilic Asthma

NgoNovemba ka-2017, i-FDA ivume i-biologic Fasenra ukuphatha i-asthma ye-eosinophilic

NgoNovemba ka-2017, i-FDA yavuma i-biologic entsha yokongeza ukonyango kwesifo se-asthma esisisigxina kwi-eosinophilic inflammation (okt, i-asthma eosinophilic) ebizwa ngokuthi yi-benralizumab (Fasenra).

Ngokutsho kwe-NIH, i-agent ye-biologic "yinto eyenziwa kwimizimba ephilayo okanye imveliso yayo kwaye isetyenziswe ekuthinteni, ukuxilongwa, okanye unyango lomhlaza kunye nezinye izifo.

I-biologic agents ziquka i-antibodies, i-interleukins, kunye ne-vaccine. "I-agent biologic ingabizwa ngokuba yi-agent biological, i-biological drug, okanye i-biologic.

Ehlabathini lonke, malunga nezigidi ezingama-315 zabantu abane-asthma. Kula bantu, phakathi kwamahlanu ne-10 ekhulwini kune-asthma enamandla kwaye, ukuba ngabafanelekile, banokuzuza ngokungenelela nge-biologic.

UFasenra Usebenza njani?

Ukuqonda indlela uFasenra asebenza ngayo, kubalulekile ukuhlolisana ubudlelwane phakathi kwama-eosinophil, uhlobo lwe-cell white white, kunye ne-asthma. Ngokuqhelekileyo, ama-eosinophils asikhusela kwiimpethu ezinama-parasitic. Nangona xa kungasebenzi ngokungafanelekanga, kunjalo, i-eosinophil ingonakalisa izicubu kwaye ibangele i-asthma. Ukuveliswa kwe-Eosinophil kunye nomsebenzi kuthonywa yi-cytokine ebizwa ngokuba yi-interleukin-5 (IL-5).

I-Fasenra i-antioclonal antibody esebenzayo malunga ne-IL-5 receptors ezise-eosinphils. Kwinqaku le-2015 elipapashwe kwiPhando loPhando lwezeMpilo kunye neNgcamango , i-Goldman kunye nabalobi bombambano bathi: "UBenalalizumab [uFasenra] ukhuthaza ngokukhawuleza, ngokukhawuleza, kwaye ngokugqithiseleyo ukuphelisa ukuchithwa kwama-eosinophil ngokusebenzisa inkqubo yokuphucula i-cytotoxicity esele ixhomekeke kwi-anti-anti-cell. ye-eosinophil ukupheliswa kokubandakanya iiseli zokubulala zendalo. "Ngokuyinene, uFasenra unxibelelanisa ukupheliswa kwama-eosinophil.

Amanye amachiza angama-monoclonal ngokubhekiselele kwi-IL-5-mepolizumab (Nucala) kunye ne-reslizumab (Cinqair) -bindela i-IL-5 kwaye ngoko kubangela ukunciphisa i-eosinophil ngokusebenzisa iindlela ezingapheliyo kunye nezingekho ngqo. Okubalulekileyo, njengoFasenra, uNucala kunye noCinqair bongeza kwizonyango.

Uvavanyo lwe-ZONDA Clinical

Ngethuba lesigaba se-Phase III ZONDA, abaphandi ba-AstraZeneca bavavanya ukuba ulawulo lwe-Fasenra lunokunciphisa imfuno yonyango lomlomo we-glucocorticoid esetyenziselwa ukugcina isifo se-asthma kwizigulane ezine-eosinophilia eziqhubekayo, okanye ukwanda kwenani lama-eosinophil egazini.

Kubaluleke kakhulu, unyango lwexesha elide kunye ne-systemic, okanye ngomlomo, i-glucocorticoids ineempembelelo ezininzi ezimbi ezichaphazela i-musculoskeletal, endocrine, i-cardiovascular, kunye neenkqubo eziphakathi kwamanzi. Abantu abasebenzisa i-glucocorticoids yomlomo ngamaxesha amade amaxesha athile bahlehliswa umgangatho wobomi. Ngelishwa, phakathi kwama-32 ukuya ku-45 ekhulwini labantu abane-asthma enamandla esele bathatha i-dose high-inhaled glucocorticoids kunye ne-bronchodilators kuxhomekeke kwixesha eliqhelekileyo (oko kukuthi, ukugcinwa) ngomlomo we-glucocorticoid unyango ukulawula i-asthma.

Kwi-trial ye-ZONDA, izigulane ezingama-369 zabhaliswe, kwaye ezi zi-220 zezi zi gulane zenziwa ngamaqela amathathu. Ngethuba lokuvavanywa kweveki ezingama-28, iqela lokuqala lokuhlola lafumana iilenki ezincinci zeFasenra rhoqo kwiiveki ezine, iqela lesibini lezilingo lafumana ijoyi ezingaphantsi kweFasenra nganye kwiiveki ezisibhozo, kwaye iqela lokulawula lafumana i-injection placebo. Ngaphezu koko, abaphandi banciphisa amanani e-glucocorticoid ngomlomo athathwe ngamaqela amathathu ukuya kwinqanaba elincinci elifunekayo ukulawula i-asthma. Abaphandi baphinde bavavanya iqondo lokunciphisa i-asthma yokunyusa, umphunga, iimpawu kunye nokukhuseleko.

Nazi iziphumo zetyala lekliniki:

• Kuzo zombini amaqela okulinga athatha iFasenra, iqondo lokugqibela lomlomo we-glucocorticoid lilinganiselwa kuma-75 ekhulwini ngaphantsi kwalawo asezantsi.

• Kwiqela le-placebo, i-dose ye-glucocorticoid yomlomo wokugqibela yomlomo yayingaphantsi kwama-25 eepesenti kunezo ezisezantsi.
• Abathathi-nxaxheba abathatha iFasenra babekho ngaphezu kwamaxesha amane ukuba banokunciphisa umthamo we-glucocorticoid ngomlomo kunabo bafumana indawo ye-placebo.
• Kwimimiselo yokuhlola ethatha i-Fasenra rhoqo kwiiveki ezine, iziganeko zokuhlaselwa kwe-asthma zonyaka zancipha ama-55 ekhulwini xa kuthelekiswa nelo qela lolawulo.
• Kwi-regimen yokulinga ethatha i-Fasenra nganye kwiiveki ezisibhozo, iziganeko zentsholongwane yokuphefumula kwe-asthma zanciphise ama-70 ekhulwini xa kuthelekiswa nelo qela lolawulo.
• Umsebenzi we-Lung njengoko ulinganiswe usebenzisa umqulu ophefumlelweyo ophefumlelweyo kwisigqi se-1 (FEV1) ayengafani kakhulu nalabo bathatha iFasenra xa kuthelekiswa nalabo bathatha indawo.

• Amaphesenti angamashumi amahlanu ezigulane ezitholwa kumlinganiselo wokuqala we-prednisone (okt, ngomlomo we-glucocorticoids), ezazingaphantsi okanye ezilingana no-12.5 mg ngosuku, zazinqanda ukusetyenziswa kwazo kwe-glucocorticoids ngokupheleleyo xa zithatha i-Fasenra.
• Imilinganiselo yokuvavanya umgangatho wobomi obunxulumene nesifuba sobomi kulabo bathatha iFasenra xa kuthelekiswa nalabo bathatha indawo. Amanye amanyathelo akhombisa ukuphuculwa kweempawu ze-asthma, kwaye abanye ababonanga utshintsho xa kuthelekiswa nezo zi gulane zithatha indawo.
• Iziganeko zeziganeko ezimbi zifana nalabo bathatha iFasenra kunye nabo bathatha indawo, ebonisa ukuba uFasenra unokukhuseleka.

Ngoko, ukuxhatshazwa kwe-asthma kubhekisela kuphi? Ngokutsho kweNair kunye nabalingane:

Ukugqithiswa kwesifo somfuzo kuchazwa ngokunyuka kwesifo se-asthma esabangela ukunyuka kwexeshana kwimizuzu ye-glucocorticoid ye-systemic ubuncinane iintsuku ezingama-3 ukunyanga iimpawu, ilungu lezithuba ezingxamisekileyo zivakatye ngenxa yesifo se-asthma esiye sabangela unyango nge-systemic glucocorticoid ngaphezu kweso sigulane imithi yokulondoloza rhoqo, okanye isifo esibhedlele esibhedlele ngenxa yesifo se-asthma.

Ngethuba lovavanyo lweZONDA, izigulane ezili-166, okanye iipesenti ezingama-75, izigulane ezithatha iFasenra zinefuthe elilodwa elibi. Nantsi ukuphazamiseka kwemiphumo emibi ephawulwe ngexesha lokuvavanywa kweklinikhi:

• I-Nasopharyngitis (iipesenti ezili-17)
• Ukuphucula i-asthma (iipesenti ezingama-13)
• I-brronchitis (iipesenti ezili-10)

Ingqalelo, i-nasopharyngitis ibhekisela ekuvukeni kwempumlo kunye nomoya ophezulu. Ixesha eliqhelekileyo kubanda libhekisela kwi-nasopharyngitis. I-brronchitis ibhekisela ekuvukeleni kwee-airways ezantsi, okanye kwiibhubhu ezinobulunga emiphakeni.

Ewonke, izigulane ezingama-28 (ama-13 ekhulwini) zenze into yokuba abaphandi babona "imiphumo engathí sina" -iyona nto ixhaphakileyo isifo somoya. Izigulane ezimbini ezithatha iFasenra zafuneka ziyeke ukusetyenziswa kweziyobisi. Ezi zigulane zombini zifayo ngexesha lelingo kodwa izizathu ezingahambelani nokulawulwa kwesigulane esisodwa seFasenra safa ngenxa yokungaphumeleli komzimba kwaye esinye safa sisifo se-pneumonia. (Zombini ezi zigulane zinezinye izifo, okanye izidumbu.)

Abaphandi baphetha ngelithi abantu abane-asthma eosiniphili, abanomdla wokulondoloza umlomo we-glucocorticoid unyango bangancinci kulabo bafumana iFasenra nganye kwiiveki ezisibhozo. Okubaluleke kakhulu, kwi-ZONDA ityala, abaphandi bafumene ukuba iziganeko zokuphefumula kwe-asthma zonyaka zancinci kubantu abathatha iFasenra nganye iveki xa kuthelekiswa nalabo bathabatha imithi nganye kwiiveki ezine.

Uvavanyo lweeKlinikhi ezongezelelweyo

Kweminye imvavanyo emibini yeeklinikhi ebizwa ngokuba ngu-SIROCCO kunye neCALIMA, abaphandi baphinde bahlola ukusebenza kweFasenra. Kule mivavanyo, eyapapashwa inyanga eziliqela phambi kweziphumo zetyala le-ZONDA, abaphandi bafumene ukuba ii-injection zangaphantsi ze-Fasenra nganye kwiinyanga ezine okanye ezisibhozo zanciphisa ukukhushulwa kwe-asthma, umsebenzi ophuculweyo we-lung (okwandisa i-FEV1) igazi elidlulileyo i-eosinophil kwiigulane ezinamaxabiso angaphezu kwama-300 amaseli / microliter. Ngaphezu koko, abaphandi bafumanisa ukuba-nangona iimvavanyo zengqinisiso zazingakhange zihlolwe-iFasenra nganye yeeveki zibonakala zisebenza ngakumbi kunokuba zilawulwe izilwanyana nganye kwiiveki ezine. Kubaluleke kakhulu, ukulawula izidakamizwa nganye kwiiveki ezisibhozo kunciphise umthwalo wemithi kwisigulane.

Ngokuxhamla, ngexesha letyala leZONDA, iipesenti ezingama-20 zezigulane ezithatha iFasenra azizange zithathwe nciphiso kwiqondo lomlomo we-glucocorticoid ngaphandle kokuba igazi le-eosinophil ezibalwe kwezi zi gulane lalifana nalabo ababenokunciphisa okukhulu kwiqondo lokugqibela lomtya we-glucocorticoid. I-Nair kunye noogxa basebenza nabo bathi "mhlawumbi ukuba khona kwegazi i-eosinophilia ayinakukuchonga i-eosinophil njengesistim esisisiseko sezinye izigulane."

Ngethuba lokuxhaswa kwe-SIROCCO kunye ne-CALIMA, i-Goldman nabaphandi bahlola ukuba i-Fasenra inganciphisa i-asthma yokunyuka kwamazinga kwizigulane kungakhathaliseki ukuba i-eosinophil ibalwa. Abaphandi bafumanise ukuba kubantu abanomlinganiselo ophezulu we-eosinophil-kubalwa ngaphezulu okanye abalingana nama-cell cell / Firenra-150 "ukunciphisa umthwalo wezifo kunye neendleko zonyango kulolu hlobo lwabantu abanzima olunokunyanga."

Ngokufanayo, izilingo zangaphambili zeklinikhi zibonise ukuba ezinye iil-antibodies ezimbini ezichasene ne-IL-5 ezikhoyo kwiimarike, i-Nucala neCinqair, ziphumelele kwizigulane ezinexabiso elingaphantsi kwe-eosinophil egazini (oko kukuthi, likhulu kuneli-150 okanye i-microliter) .

Ngokuqhelekileyo, imilinganiselo yegolide yokuxilongwa kwe-asthma ye-eosinophilic ibandakanya ukuboniswa kokuvuvukala kwi-airways ye-bronchial esekelwe kuviwo lwe-biopsy okanye i-sputum. Le nkqubo, kunjalo, kunzima ukwenza kwaye ifuna uqeqesho olulodwa; Ngoko ke, abaqeshwanga rhoqo. Kunoko, oogqirha bancike kwiibalo ze-eosinophil zegazi, okokuba nangona kulandelelana kwesifo se-asthma, asifezekanga. Ukongezelela, i-eosinophil ibalwa kakhulu ngokuxhomekeke kwixesha kwaye iyakhathalela unyango lwe-corticosteroid.

Ngokutsho kweGoldman kunye nababhali-mbhali:

Iziphumo zohlalutyo lwangoku zixhomekeke ekunciphiseni kwamandla okuchaza abaphenduli abasenokwenzeka kwi-eosinophil ukunyusa unyango, ngokusekelwe kwigazi le-eosinophil inani lama-300 cells / microliter] yedwa. Ukubonakaliswa ngokubanzi kwenkcazelo ye-eosinophilic phenotype ngaphaya kwegazi le-eosinophil zibalo ezifunekayo ezisebenzisa ukudibanisa iimpawu zeklinikhi (umz., I-polyposis yamanzi), kunye nokubala kwegazi eosinophil. Iingxelo zegazi ze-eosinophil kufuneka zilinganiswe kwiindawo eziliqela zexesha ukujongana nemiba yokuhlukahluka okubangela ukuba ufumane ukuxilongwa kwezigulane ezine-eosinophilic inflammation.

Fasenra ngokumalunga neKhuphiswano

Okwangoku, akucaci indlela uFasenra atyelela ngayo ezinye i-biologics ezijolise kwi-IL-5: iNucala neCinqair. Kwinqaku ebizwa ngokuthi "uBenalalizumab unyango lwe-asthma," uSobo kunye nabalobi ababambisene nabo babhala ukuba uFasenra mhlawumbi ufuna i-dosing ephindaphindiweyo kuneNucala noCinqair. Nangona kunjalo, abaphandi babhala oku oku malunga nokuthelekiswa kwezi zonyango ezintathu:

Olunye uphuculo kwiimpawu zesifo se-asthma kunye nomgangatho wobomi kuvela kuzo zonke i-biologics ezintathu, kodwa iinjongo zekliniki ezi zinto ziphuculwa ngokucacileyo. ... Kuze kube lula ukulinganisa izilingo ezilawulwa ngokungafaniyo, ezintathu zikhetha ukukhetha phakathi kwabo unyango lwe-asthma eosinophilic.

I-AstraZeneca, umenzi we-Fasenra, icebo lokuxabisa ixabiso elingaphantsi kweNucala neCinqair, enye i-IL-5 yezinto eziphilayo ezikhoyo kwi-market. Nangona amaxabiso eziyobisi ahluka ngokuxhomekeka kwizinto eziliqela, ngokwezinto ezithile ukuqikelela, i-Nucala ibiza malunga ne-$ 32,500 ngonyaka, kunye neCinqair iindleko ezifanayo. Ekugqibeleni, ngenxa yokuba iFasenra inokulawulwa ngokungaphantsi kwezinye i-biologics, ixabiso liya kuba liphantsi.

> Imithombo:

> Goldman M et al. Ubambiswano phakathi kwegazi le-eosinophil count kunye ne-benralizumab ukuphumelela kwezigulane ezine-asthma ezingavumelekanga: ii-subanalyses zeSigaba III SIROCCO kunye noCALIMA. Uphando lwezoPhando kunye neNgxelo . 2017; 33: 1605-1613. https://doi.org/10.1080/03007995.2017.1347091.

> Nair P et al. Impembelelo ye-Glucocorticoid-Impembelelo ye-Benralizumab kwi-Asthma enamandla. I-New England Journal of Medicine . 2017; 376: 2448-58. https://doi.org/10.1056/NEJMoa1703501.

> Saco TV et al. Benralizumab unyango lwe-asthma. Ukuphononongwa kweNgcali ye-Clinical Pharmacology. Ukuphononongwa kweNgcali ye-Clinic Immunology . 2017; 13 (5): 405-413. http://www.tandfonline.com/doi/full/10.1080/1744666X.2017.1316194.

> Wardlaw AJ. I-Eosinophil kunye neengxaki ezinxulumene nazo. Ku: Kaushansky K, Lichtman MA, Prchal JT, Levi MM, Press OW, Burns LJ, Caligiuri M. eds. Williams Hematology, 9e eNew York, NY: McGraw-Hill