MunaNovember 2017, FDA yakabvuma Fasenra biologic kuti iite zvirwere zvisingaiti
MunaNovember 2017, FDA yakabvumira bhulogi itsva kuti iwedzere-pane kurapwa kwechirwere chechipiri chechirwere chechirwere chechirwere chechirwere chechiremera (kureva kuti, eosinophilic asthma) inonzi benralizumab (Fasenra).
Maererano neNIH, mhizha ye "biologic" inonzi "chinhu chinogadzirwa kubva mumuviri mhenyu kana mishonga yayo uye inoshandiswa mukudzivirira, kuongororwa, kana kurapwa kwekenza nedzimwe zvirwere.
Biologic agents dzinosanganisira antibodies, interleukins, uye zvirwere. "A biologic agent anogonawo kunzi aine biologist, biological drugs, kana biologic.
Munyika yose, vanenge mamiriyoni 315 vane chirwere chemafi. Pakati pevanhu ava, pakati pe5 ne10 muzana vane chirwere chakanyanya uye, kana vakakodzera, vanogona kubatsirwa nekupindira ne biologic.
Fasenra Inoshanda Sei?
Kuti unzwisise kuti Fasenra anoshanda sei, zvakakosha kuongorora hukama huri pakati peEosinophils, chimiro chechichena cheropa, uye asthma. Kazhinji, eosinophils inotidzivirira pamaronda ane chirwere. Kana zvisina kukodzera kushandiswa, zvakadaro, eosinophils inogona kukuvadza mishonga uye inokonzera chipfu. Eosinophil kugadzirwa uye basa rinokonzerwa ne cytokine inonzi interleukin-5 (IL-5).
Fasenra inonzi monoclonal antibody inopesana neI-5 receptors iri pane eosinphils. Muna Nyaya ya2015 yakabudiswa muAradic Medical Research neMafungiro , Goldman uye vanyori vanyori vanotaura zvinotevera: "Benralizumab [Fasenra] inotungamirira zvakananga, nokukurumidza, uye inopedzisa kupera kwemaoinophils kuburikidza nekuwedzerwa kwe-antibody-dependent cell-mediated cytotoxicity, chirongwa chepoptotic yeEosinophil kubviswa kunobatanidza kuuraya masero emunhu. "Chaizvoizvo, Fasenra anopindira kubviswa kwemashoko eosinophils.
Zvimwe zvinokonzerwa ne-monoclonal anti-IL-5-mepolizumab (Nucala) uye reslizumab (Cinqair) -bind IL-5 uye zvinokonzera kuderedzwa kweeosinophil kuburikidza nehuwandu husina maturo uye nzira dzisinganzwisisiki. Zvakakosha, saFasenra, zvose Nucala naCinqair vari kuwedzera-pane kurapwa.
ZONDA Clinical Trial
Munguva yePatatu III ZONDA muedzo, vatsvakurudzi veA AstraZeneca vakaongorora kana kutungamirirwa kweFasenra kunogona kuderedza kudiwa kwetachiona glucocorticoid therapy inoshandiswa kuchengetedza chirwere chechirwere muvarwere vanoramba vachinyora eosinophilia, kana kuwedzera kwenhamba yeeosinophils muropa.
Zvakakosha, kurapwa kwenguva refu ne systemic, kana muromo, glucocorticoids ine zvakawanda zvakaipa zvinogumbura zvinokonzera musculoskeletal, endocrine, mwoyo, uye midzi yenheyo. Vanhu vanotora muromo glucocorticoids kwenguva yakareba ruzivo rwakaderedza hupenyu hwehupenyu. Zvinosuruvarisa, pakati pe 32 ne45 muzana yevanhu vane chirwere chakasimba chinenge chakatora mishonga inoputika glucocorticoids uye bronchodilators vanovimba nguva dzose (kureva, kuchengetedza) muromo weglucocorticoid therapy kuti uchengetedze mweya yavo.
Muchiitiko cheZONDA, varwere 369 vakanyoresa, uye 220 vevashandi ava vakaiswa mumapoka matatu. Munguva yekutongwa kwevhiki-28, boka rekutanga rekuongorora rakawana zvirwere zviduku zveFasenra masvondo mana ose, boka rechipiri rekuongorora rakawana majekiseni mashomanana eFasenra masvondo masere ose, uye boka rinodzora rakagamuchira placebo injections. Uyezve, vatsvakurudzi vakaderedza miviri yeglucocorticoid yakatorwa nemapoka ose matatu kusvika pane zvishoma zvakakosha kuti utadze chirwere. Vatsvakurudzi vakaongororawo gore negore kuwedzera kwehuputi hwemafi, mapapu ekushanda, zviratidzo, nekuchengeteka.
Heano mhinduro dzekuongorora kwechipatara:
- Mune mapoka maviri ekuedza kutora Fasenra, miviri yekupedzisira yemuromo glucocorticoid yaive ye75 muzana yakaderera pane yepakutanga.
- Muboka re-placebo, chirwere chekupedzisira chemukati glucocorticoid chaive ne25 muzana pasi kune avo vari panotangira.
- Vatori vemutora vachitora Fasenra vakanga vanopfuura katatu zvichida kuti vawane kuderedzwa kwemuromo weglucocorticoid dose kune avo vanogamuchira nzvimbo.
- Muchirongwa chekuedza chinotora Fasenra vhiki dzose dzechina, kukanganisa kwegore negore kwekuwedzera kwemafiya kwakaderera 55 muzana kana ichienzaniswa neyeboka rekutonga.
- Muchirongwa chekuedza chinotora Fasenra vhiki masere masere, kukanganisa kwegore negore kwekuwedzera kwemafiya kwakaderera 70 muzana kana ichienzaniswa neyeboka rekutonga.
- Chiremera chinoshandiswa kuburikidza nekushandiswa zvakamanikidzwa kuporesa ivhu mugore re1 (FEV1) chakanga chisina kunyanya kune avo vanotora Fasenra kana vachienzanisa nevaya vanotora placebo.
- Zvikamu makumi mashanu kubva muzana zvevarwere vanowana zvinyorwa zvekutanga zvinonzi prednisone (kureva, oral glucocorticoids), izvo zvisingasviki kana zvakaenzana ne12.5 mg pazuva, vakakwanisa kurega kushandisa kwavo glucocorticoids zvakakwana pavanotora Fasenra.
- Nzira dzinoongorora hutano hwehupenyu hwehutachiona hwehupenyu kune avo vanotora Fasenra kana vachienzaniswa nevaya vanotora placebo vakavhenganiswa. Zvimwe zviyero zvakaratidza kuvandudza muzviratidzo zvechirwere, uye vamwe havana kuratidza kuchinja kana vachienzaniswa nevaya vaitora placebo.
- Izvo zviitiko zvezviitiko zvakashata zvakafanana kune avo vanotora Fasenra nevaya vanotora placebo, izvo zvinoratidza kuti Fasenra inogona kunge yakachengeteka.
Saka, kuwedzera kwekusimba kunorevei? Maererano Nair navanoshanda navo:
Kuwedzera kwekusimudzira mweya kwakarondedzerwa sekuwedzera kuwedzera kwechirwere chakaita kuti kuwedzerwa kwenguva pfupi mumuviri we systemic glucocorticoid kwemazuva matatu kuti utarise zviratidzo, kushanyirwa kwebasa rekukurumidzira kunokonzerwa nechirwere chinotungamirira kuchirapa ne-systemic glucocorticoid kuwedzera kumurwere nguva dzose mishonga yekugadzirisa, kana kuti inpatient hospitalization nekuda kwechirwere.
Munguva yekutongwa kwaZONDA, vatanhatu 166, kana 75 muzana, yevarwere vanotora Fasenra vakawana zvinenge zvakashata. Heano kuparara kwemigumisiro yakaipa yakaonekwa panguva yekuedzwa kwechipatara:
- Nasopharyngitis (17 muzana)
- Kuwedzera mafimma (13 muzana)
- Bronchitis (10 muzana)
Nenzira, nasopharyngitis inoreva kuvhuvhuta kwemhino nepamusoro pemhepo. Izwi izwi rinowanzoshandiswa rinoreva nasopharyngitis. Bronchitis inoreva kuvhuvhuta kwemhepo yakadzika, kana maronchial tubes mumapapu.
Pose, 28 varwere (13 muzana) vakawana izvo vatsvakurudzi vakaona "zvakakomba" zvinokanganisa-zvakanyanya kuwedzera kuwedzera kushaya mweya. Varwere vaviri chete vanotora Fasenra vaifanira kurega chirwere. Vashandi ava vaviri vakafa munguva yekuedzwa asi zvikonzero zvinopesana nehutungamiri hweFasenra-mumwe murwere akafa nekuda kwekushaya mwoyo uye imwe yakafa nepineumonia. (Vose varwere ava vaiva nezvimwe zvirwere zvakawanda, kana kuti comorbidities.)
Vatsvakurudzi vakagumisa kuti kune vanhu vane mafi emainiinifi, simba rekuchengetedza glucocorticoid therapy rinogona kuderedzwa kune avo vakagamuchira Fasenra vhiki masere masere. Zvakakosha, mumuedzo weZONDA, vatsvakurudzi vakaona kuti kuitika kwegore negore kwekuwedzera kwemafiya kwakanyanyisa kuderera kune vanhu vanotora Fasenra vhiki imwe neimwe masere kana vachienzaniswa nevaya vanotora mishonga vhiki imwe neimwe.
Zvimwe Zvipatara Zvimwe
Mune mamwe maviri emakiriniki anonzi SIROCCO naCALIMA, vatsvakurudzi vakaongororawo Fasenra kubudirira. Mune miedzo iyi, iyo yakabudiswa mwedzi yakaverengeka mberi kwemigumisiro yeruzhinji rweZONDA, vatsvakurudzi vakawana kuti majekiseni eAppcutaneous yeFasenra mavhiki mana kana masere masere akaderedza kuwedzera kwemafupa, kuwedzera mapapu emabasa (kureva, kuwedzera mararamiro eFIV1), kuwedzerwa zviratidzo zvekuita, uye yakazara ropa eosinophils kune varwere vane nhamba dzinopfuura 300 masero / microliter. Uyezve, vakatsvakurudza vakawana kuti-kunyange zvazvo kuongororwa kwemaitiro kusingatariswi-kutora Fasenra masvondo masere ose akaonekwa sekubudirira kupfuura kutungamirira mishonga kwevhiki ina dzose. Zvinonyanya kukosha, kutungamirira chirwere ichi kwemavhiki masere ose kwakaderedza mutoro wemishonga kumurwere.
Zvinonzwisisika, panguva yekutongwa kwaZONDA, 20 muzana yevarwere vanotora Fasenra havana kugona kuderedza mumuromo we glucocorticoid doses kunyange zvazvo ropa eosinophil kukosha kwevarwere ava vakanga vakafanana neavo vakave nekuderedza kukuru kwemazwi avo ekupedzisira glucocorticoid. Nair nevamwe vashandi vanofungidzira kuti "zvichida kuvapo kweropa eosinophilia kunogona kusingazivi kuti eosinophil sechinhu chinokonzera masero mune vamwe varwere."
Pakati pekutsvaga kweSIROCCO neCALIMA miedzo, Goldman nevatsvakurudzi vakaongorora kana Fasenra aigona kuderedza kuwedzera kwehutachiona hwemhepo kune varwere zvisinei nokuti eosinophil inoratidzei. Vatsvakurudzi vakawana kuti kune vanhu vane eosinophil yepamusoro-inhamba yakakura kudarika kana yakaenzana nemaseli 150 / microliter-Fasenra "inoderedza mutoro wezvirwere uye kutarisira utano hwehutano hwehuwandu hwakaoma-kubata-huwandu husingagoni kurapa zvishoma."
Saizvozvowo, zviitiko zvekuchirapa zvekare zvakaratidza kuti mamwe maviri e-anti-IL-5 iye zvino pamusika, Nucala naCinqair, anobatsira kune varwere vane madiki eosinophil anoverengera muropa (kureva, guru kupfuura kana rakaenzana nemaseli 150 / microliter) .
Kazhinji, chiyero chegoridhe chekucherechedza kwechirwere chekusagadzikana chinosanganisira kutaridzika kwekuvhiringidza mumhepo inopisa mhepo inobva pakuongorora kwebiopsy kana kuti inokonzerwa nemhepo inonzi sputum. Iyi nzira, zvisinei, zvakaoma kuita uye zvinoda kudzidziswa kwakakosha; saka, havasi kushandiswa nguva dzose. Pane kudaro, vanachiremba vanovimba nezveropa reososophil, izvo izvo kunyangwe kufungidzira kwekuoma kwechirwere, hazvina kukwana. Uyezve, eosinophil inoratidzika zvakasiyana-siyana zvichienderana nenguva uye inofanirwawo nekodticosteroid.
Maererano naGoldman uye vanyori vanyori:
Zvigumisiro zvemazuva ano zvinotsanangura zvinogona kuita zvingave zvisingakwanisi kurondedzera vanopindura vangangodaro kuEosinophil kuderedza chirwere, zvichienderana neropa reososopop count ye [300 cells / microliter] oga. Zvimwe zvakanyatsorondedzerwa zvisinganzwisisiki zvinonzi phenotype zvisingaverengeki eosinophil zvido zvinoshandiswa izvo zvinoshandisa kusanganiswa kwezvipatara zviratidzo (semuenzaniso, nasal polyposis), pamwe neropa reososophil kuverenga. Ropa eosinophil kuverenga rinofanirwa kuyerwa pane dzimwe nguva nguva dzekutarisa nyaya dzakasiyana-siyana dzinogona kukonzera kutadza kuongororwa kune varwere vane kuvhiringidzika kwekusagadzikana.
Fasenra vs. Kurwisana
Pari zvino, hazvina kunyatsojeka kuti Fasenra inopesana sei nedzimwe biologics iyo inofanirwa IL-5: Nucala naCinqair. Mune imwe nyaya yakanzi "Benralizumab yekurapa kwemafi," Saco uye vanyori vanyori vanyorera kuti Fasenra inogona kunge inoda kudarika nguva refu kupfuura Nucala naCinqair. Zvisinei, vatsvakurudzi vanonyorawo zvinotevera maererano nekuenzanisa kwemishonga mitatu:
Dzimwe humwe hunovandudzwa muhutachiona hwechirwere uye hupenyu hwehupenyu hunowanikwa nehutatu hwehupenyu hwehupenyu, asi chirwere chinoratidzira chekuvandudza uku hachina kujeka ... Kusvikira unhu hunotaridzika hunotaridzika hunofanidza zvakaenzana zvitatu, kusarudza pakati pavo mukurapa kwekusagadzikana kwechirwere kunoramba kuchioma.
AstraZeneca, uyo ari muiti weFasenra, anoronga kutengesa mushonga wepamusoro kupfuura Nucala naCinqair, imwe yezve-add-on IL-5 biologics ikozvino pamusika. Kunyange zvazvo mutengo wemishonga unosiyana zvichienderana nezvimwe zvinhu, maererano nezvimwe zvinofungidzira, Nucala inodhura madhora 32 500 pagore, uye Cinqair inodhura zvakafanana. Pakupedzisira, nokuti Fasenra inogona kutarisirwa kashoma kudarika idzi idzi dzehupenyu, mutengo waizovawo wakaderera.
> Sources:
> Goldman M et al. Kushamwaridzana pakati pegazi eosinophil count uye benralizumab kubudirira kune varwere vane chirwere chakasimba, chisina kudzora chemasikati: subanalyses yePaul III SIROCCO uye zvidzidzo zveCALIMA. Research Current Medical and Opinion . 2017; 33: 1605-1613. https://doi.org/10.1080/03007995.2017.1347091.
> Nair P et al. Mushonga weGlucocorticoid-Kupararira Kwemagariro eBenralizumab muAsmafu Asthma. The New England Journal of Medicine . 2017; 376: 2448-58. https://doi.org/10.1056/NEJMoa1703501.
> Saco TV et al. Benralizumab yekurapa kwemafi. Ongororo Ongororo yeKliniki Pharmacology. Ongororo Ongororo yeKliniki Immunology . 2017; 13 (5): 405-413. http://www.tandfonline.com/doi/full/10.1080/1744666X.2017.1316194.
> Wardlaw AJ. Eosinophils uye Matambudziko Akafanana. Mu: Kaushansky K, Lichtman MA, Prchal JT, Levi MM, Press OW, Burns LJ, Caligiuri M. eds. Williams Hematology, 9e New York, NY: McGraw-Hill