Mu November 2017, FDA inavomereza Fasenra ya biologic kuti ikhale ndi mphumu ya eosinophilic
Mu November 2017, a FDA adavomereza kachilombo katsopano kuti awonjezeko mankhwala opatsirana a mphumu yachiwiri yopweteka kwambiri (kutanthauza kuti mpweya wotchedwa eosinophilic astmma) wotchedwa benralizumab (Fasenra).
Malinga ndi NIH, wothandizira biologic ndi "chinthu chopangidwa kuchokera ku zamoyo kapena zogulitsa zake ndipo amagwiritsidwa ntchito popewera, matenda, matenda kapena khansa.
Akatswiri a zamoyo amaphatikizapo ma antibodies, interleukins, ndi katemera. "Wothandizira biologic angathenso kutchedwa mankhwala, tizilombo toyambitsa matenda, kapena biologic.
Padziko lonse, anthu pafupifupi 315 miliyoni ali ndi mphumu. Mwa anthuwa, pakati pa asanu ndi 10 peresenti ali ndi mphumu yoyipa ndipo, ngati ali oyenera, angapindule ndi kulowerera ndi biologic.
Kodi Fasenra Amagwira Ntchito Bwanji?
Kuti mumvetse momwe Fasenra amagwirira ntchito, ndikofunika kuyesa mgwirizano pakati pa ma eosinophils, mtundu wa selo loyera, ndi mphumu. Kawirikawiri, eosinophils amatiteteza ife parasitic mphutsi. Komabe, ngati sagwiritsidwa ntchito molakwika, mavitamini amatha kusokoneza minofu ndipo amachititsa mphumu. Kupanga ndi kuyendetsa ma Eosinophil kumayendetsedwa ndi cytokine yotchedwa interleukin-5 (IL-5).
Fasenra ndi antioclonal antibody yogwira ntchito pa IL-5 receptors yomwe ili pa eosinphils. Mu nkhani ya 2015 yomwe yafalitsidwa mu Current Medical Research ndi Opinion , Goldman ndi olemba anzawo amanena izi: "Benralizumab [Fasenra] imapangitsa kuti munthu asamawonongeke mofulumira, mofulumira, ndi kumaliza kukwanira kwa maselo a eosinophil kupyolera mu cytotoxicity yowonjezeredwa ndi anti-anti-anti-antibody. za kuwonongeka kwa eosinophil kamene kamayambitsa maselo achilengedwe. "Mwachidziwitso, Fasenra amalimbikitsa kuthetseratu zinyama.
Matenda ena a monoclonal motsutsana ndi IL-5-mepolizumab (Nucala) ndi reslizumab (Cinqair) -bind IL-5 ndipo motero amachititsa kuchepa kwa eosinophil kudzera njira zowonjezera komanso zosalunjika. Chofunika kwambiri, monga Fasenra, Nucala ndi Cinqair akuwonjezera mankhwala.
ZONDA Yoyesedwa
Ofufuza a AstraZeneca akuyesa kufufuza kuti Fasenra athe kuchepetsa vuto la mankhwala okhudza glucocorticoid kuti athetse vuto la mphumu kwa odwala omwe ali ndi matenda osokoneza bongo, kapena kuti kuwonjezeka kwa magazi.
Chofunika kwambiri, mankhwala a nthawi yaitali ndi systemic, kapena oral, glucocorticoids ali ndi zotsatira zoipa zambiri zomwe zimakhudza minofu, endocrine, mtima, ndi machitidwe apakati. Anthu amene amatenga glucocorticoids kwa nthawi yaitali amakhala ndi khalidwe labwino. Mwamwayi, pakati pa 32 ndi 45 peresenti ya anthu omwe ali ndi mphumu yambiri yomwe ayamba kale kumwa mankhwala a glucocorticoids ndi bronchodilator amadalira nthawi zambiri (ie, kusamalira) mankhwala opatsirana pogwiritsa ntchito glucocorticoid kuti athetse mphumu yawo.
Mu chiyeso cha ZONDA, odwala 369 analembetsa, ndipo odwala makumi awiri ndi makumi awiri ndi awiriwo anali oposa atatu m'magulu atatu. Pakati pa mayesero 28 a sabata, gulu loyesa kuyesera linalandira majekeseni ochepa a Fasenra masabata onse anayi, gulu lachiwiri loyesera linalandira zilonda zamkati mwa Fasenra masabata asanu ndi atatu, ndipo gulu lolamulira linalandira jekeseni wa placebo. Komanso, ochita kafukufukuwo adachepetsa mlingo wa glucocorticoid wotengedwa ndi magulu onse atatu kupita kumsika wochepa kuti athetse mphumu. Ofufuzawo adafufuzanso kuchuluka kwa chifuwa cha mphumu, kupuma, zizindikiro, ndi chitetezo.
Nazi zotsatira za mayesero a zachipatala:
- Mu magulu awiri omwe akuyesera Fasenra, mlingo womaliza wamkati wa glucocorticoid mlingo unali 75 peresenti poyerekeza ndi omwe ali pachiyambi.
- Mu gulu la placebo, mlingo womaliza wamlomo wa glucocorticoid mlingo unali 25 peresenti yochepa kusiyana ndi yomwe ili pachiyambi.
- Ophunzira omwe amatenga Fasenra anali ocheperapo katatu kuti athe kuchepetsa mlingo wa glucocorticoid mlingo kuposa omwe amalandira malo okhalamo.
- Mu kafukufuku wogwiritsira ntchito Fasenra milungu iwiri iliyonse, kuwonjezeka kwa chaka ndi chaka cha kuchuluka kwa mphumu kunachepa 55 peresenti poyerekezera ndi gulu la olamulira.
- Mu kafukufuku wogwiritsa ntchito Fasenra masabata asanu ndi atatu aliwonse, kuwonjezereka kwa chaka ndi chaka cha kuchuluka kwa mphumu kunachepera 70 peresenti poyerekezera ndi gulu la olamulira.
- Ntchito yamapiko yomwe imayesedwa pogwiritsira ntchito voliyumu yowonjezereka mu mphindi 1 (FEV1) siinali yosiyana kwambiri ndi iwo omwe amachititsa Fasenra poyerekeza ndi omwe amatenga placebo.
- Oposa makumi asanu pa 100 a odwala omwe amalandira mankhwala oyambirira a prednisone (mwachitsanzo, oral glucocorticoids), omwe anali osachepera kapena ofanana ndi 12.5 mg pa tsiku, anatha kuthetsa kugwiritsa ntchito oral glucocorticoids panthawi yomwe anatenga Fasenra.
- Njira zomwe zimayendera moyo wokhudzana ndi mphumu mwa iwo omwe amatenga Fasenra poyerekeza ndi omwe amatenga placebo anali osakaniza. Zina zinawonetsa kusintha kwa zizindikiro za mphumu, ndipo ena sanasonyeze kusintha kusiyana poyerekeza ndi odwala omwe amakhala ndi placebo.
- Nthaŵi zambiri zochitika zovuta zinali zofanana ndi omwe amatenga Fasenra ndi omwe amatenga placebo, zomwe zimasonyeza kuti Fasenra mwachiwonekere ali otetezeka.
Kotero, kuchulukitsa kwa mphumu kumatanthauzanji? Malingana ndi Nair ndi anzake:
Kuwonjezereka kwa mphumu kunatanthawuza kuti kuwonjezereka kwa mphumu komwe kunachititsa kuti pang'onopang'ono kuwonjezeka kwa mlingo wa systemic glucocorticoid kwa masiku osachepera atatu kuti athe kuchiza zizindikiro, kuyendera daladzidzidzi chifukwa cha mphumu yomwe inachititsa chithandizo ndi systemic glucocorticoid kuwonjezera pa wodwalayo mankhwala osamalidwa nthawi zonse, kapena chipatala cha chipatala chifukwa cha mphumu.
Pakati pa milandu ya ZONDA, odwala 166, kapena 75 peresenti, odwala omwe akudwala Fasenra adakumanapo ndi zotsatira zowawa. Pano pali kuwonongeka kwa zotsatira zoipa zomwe zachitika panthawi ya kuyezetsa magazi:
- Nasopharyngitis (17 peresenti)
- Kupuma mphumu (13 peresenti)
- Bronchitis (10 peresenti)
Ndipotu, nasopharyngitis imatanthawuza kutupa kwa mphuno ndi kumtunda wapamwamba. Mawu akuti chimfine wamba amatanthauza nasopharyngitis. Bronchitis imatanthawuza kutupa kwa m'munsi mwa airways, kapena mazira omwe amapezeka m'mapapu.
Onsewa, odwala 28 (13 peresenti) adziwona zomwe ochita kafukufuku adawona kuti "zoopsa" zowononga-zofala kwambiri kuwonjezereka ndi mphumu. Odwala awiri okha omwe amatenga Fasenra ayenera kusiya mankhwalawa. Odwala awiriwa anafera panthawi ya milandu koma zovuta zogwirizana ndi olamulira a Fasenra-mmodzi anafa ndi kulephera kwa mtima ndipo wina anafa ndi chibayo. (Odwalawa onse anali ndi matenda ena ambiri, kapena comorbidities.)
Ofufuzawa anapeza kuti anthu omwe ali ndi mphumu yambiri ya eosiniphilic, mankhwalawa amachepetsedwa mwa iwo omwe analandira Fasenra milungu isanu ndi itatu. Chofunika kwambiri, mu chiwonetsero cha ZONDA, ofufuza adapeza kuti kuwonjezereka kwa nyenyezi kwa chaka ndi chaka kunali kochepa pakati pa anthu omwe amatenga Fasenra milungu isanu ndi itatu poyerekeza ndi omwe amamwa mankhwala tsiku lililonse.
Zowonjezera Zowonjezereka
Mu mayesero ena awiri a zachipatala otchedwa SIROCCO ndi CALIMA, ofufuza adafufuzanso mphamvu ya Fasenra. M'mayesero awa, omwe anafalitsidwa miyezi ingapo zisanachitike zotsatira za chiwonetsero cha ZONDA, ofufuza adapeza kuti majekeseni a Fasenra omwe amagwiritsidwa ntchito pochepa amatha kuchepetsa kuwonjezereka kwa mphumu, kupuma kwa mapapo (ie, kuwonjezera miyeso ya FEV1); magazi ochepa omwe amatha kukhala odwala omwe ali ndi ziwerengero zoposa 300 maselo / microliter. Komanso, ochita kafukufukuwa adapeza kuti ngakhale kuti mayesero sakuwerengedwa-Fasenra imafika patatha masabata asanu ndi atatu onse akuwoneka bwino kwambiri kuposa momwe amachitira mankhwalawa milungu iwiri iliyonse. Chofunika kwambiri, kupereka mankhwala kwa milungu isanu ndi itatu yachepa kunachepetsanso mankhwala.
Chodabwitsa, panthawi ya mlandu wa ZONDA, 20 peresenti ya odwala omwe amachititsa Fasenra sanachepetsere mankhwala amtundu wa glucocorticoid ngakhale kuti magazi a eosinophil a odwalawa anali ofanana ndi omwe anali ndi kuchepa kwakukulu kwa mankhwala omaliza a glucocorticoid. Nair ndi anzake amaganiza kuti "mwinamwake kupezeka kwa magazi eosinophilia sikungadziŵe kuti eosinophil ndi selo yaikulu yowonetsera odwala ena."
Pogwiritsa ntchito mayesero a SIROCCO ndi CALIMA, Goldman ndi ofufuza anafufuza ngati Fasenra akhoza kuchepetsa chiwerengero cha kuchuluka kwa mphumu kwa odwala mosasamala kanthu za chiwerengero cha eosinophil. Ofufuzawa adapeza kuti mwa anthu omwe ali ndi chiwerengero chochepa cha oosinophil choposa kapena chofanana ndi maselo 150 / microliter-Fasenra "amachepetsa kulemetsa kwa matenda ndi chisamaliro kwa anthu ovutawa kuchiza omwe alibe njira zochepetsera mankhwala."
Mofananamo, mayesero am'mbuyo am'mbuyo awonetsetsa kuti ma antibodies awiri omwe amatsutsana ndi IL-5 omwe ali pamsika, Nucala ndi Cinqair, amagwira ntchito odwala omwe ali ndi chiwerengero chochepa cha m'magazi (ie, wamkulu kapena wofanana ndi maselo 150 / microliter) .
Kawirikawiri, muyezo wa golidi wa matenda a mphumu ya eosinophilic umaphatikizapo kujambula kwa kutupa mumphepete mwawombankhanga pogwiritsa ntchito kufufuza kwa biopsy kapena kumayambitsa matendawa. Njirazi, komabe, n'zovuta kuchita ndipo zimafuna maphunziro apadera; Choncho, iwo sagwiritsidwa ntchito nthawi zonse. M'malo mwake, odwala amadalira kuwerengera kwa magazi a eosinophil, omwe ngakhale atakhala ndi vuto la chifuwa cha mphumu, alibe ungwiro. Komanso, eosinophil amasiyana kwambiri malinga ndi nthawi komanso amatha kuchiritsidwa ndi mankhwala a corticosteroid.
Malingana ndi Goldman ndi alembi ena:
Zotsatira za zomwe zikuchitika pakali pano zimatsimikizira zolephera zomwe zingathe kufotokozera anthu omwe angayankhe kuti athetse vutoli, motengera magazi ochepa omwe amakhala [300 cells / microliter] okha. Kuwonetseratu mwatsatanetsatane ka maosophephisitiki omwe amatha kupitirira magazi a eosinophil ndi osowa omwe amagwiritsa ntchito kuphatikiza mazinthu zam'chipatala (mwachitsanzo, nasal polyposis), pamodzi ndi chiwerengero cha magazi a eosinophil. Malipoti a magazi a eosinophil ayenera kuyesedwa pa nthawi zingapo kuti athetse mavuto omwe angayambitse odwala omwe ali ndi kutupa kwa eosinophilic.
Fasenra vs. Mpikisano
Pakalipano, sizikudziwika bwino momwe Fasenra amanyamulira motsutsana ndi zamoyo zina zomwe zimalimbikitsa IL-5: Nucala ndi Cinqair. M'nkhani yomwe imatchedwa "Benralizumab kuti ayambe kuchiza mphumu," Saco ndi alembi amalemba kuti Fasenra amafunanso kuchepetsa vutoli kuposa Nucala ndi Cinqair. Komabe, ochita kafukufuku amalembanso zotsatirazi poyerekezera ndi mankhwala atatuwa:
Zina mwazochita zowonjezera zizindikiro za chifuwa cha asthma ndi khalidwe la moyo zimakhala ndi zamoyo zonse zitatu, koma kutanthauzira kwachidziwitso kwa kusintha kumeneku sikungakhale kosavuta.
AstraZeneca, yemwe amapanga Fasenra, akukonzekera kugula mankhwala osokoneza bongo kuposa Nucala ndi Cinqair, ena omwe ali ndi bi-biological zowonjezera za IL-5 omwe ali pa msika. Ngakhale mitengo ya mankhwala imasiyanasiyana malinga ndi zifukwa zingapo, malinga ndi zifukwa zina, Nucala imadya madola 32,500 pachaka, ndipo Cinqair amawononga mofanana. Pomalizira, chifukwa Fasenra ikhoza kuperekedwa mobwerezabwereza kuposa mabungwe ena ena, mtengowo udzakhala wotsika.
> Zotsatira:
> Goldman M et al. Chiyanjano pakati pa magazi eosinophil count ndi benralizumab zothandiza kwa odwala omwe ali ndi mphumu yovuta, yosalamulirika: ma subanalyses a Phase III SIROCCO ndi maphunziro a CALIMA. Zofufuza Zamakono Zamakono ndi Maganizo . 2017; 33: 1605-1613. https://doi.org/10.1080/03007995.2017.1347091.
> Nair P et al. Mmene Mankhwala Ogwiritsira Ntchito Amagwiritsira Ntchito Mankhwalawa Amakhudza Benralizumab mu Chisokonezo Choopsa. The New England Journal of Medicine . 2017; 376: 2448-58. https://doi.org/10.1056/NEJMoa1703501.
> Saco TV ndi al. Benralizumab pofuna kuchiza mphumu. Kukambirana kwa akatswiri a Clinical Pharmacology. Kufufuza kwa akatswiri a Clinic immunology . 2017; 13 (5): 405-413. http://www.tandfonline.com/doi/full/10.1080/1744666X.2017.1316194.
> Wardlaw AJ. Matenda a Eosinophil ndi Matenda Okhudzana Nawo. Mu: Kaushansky K, Lichtman MA, Prchal JT, Levi MM, Press OW, Burns LJ, Caligiuri M. eds. Williams Hematology, 9e New York, NY: McGraw-Hill