natgillin/translations-raw huggingface dataset:
In the European Union, as of 30 November 2017, daclizumab beta has been marketed in Austria, Belgium, Denmark, Finland, Germany, Ireland, Italy, Netherlands, Norway, Poland, Slovenia, Sweden and United Kingdom.
Od 30. studenoga 2017. daklizumab beta stavljen je u promet u Europskoj uniji u Austriji, Belgiji, Danskoj, Finskoj, Njemačkoj, Irskoj, Italiji, Nizozemskoj, Norveškoj, Poljskoj, Sloveniji, Švedskoj i Ujedinjenoj Kraljevini.
National competent authorities competent for the regulatory oversight of these clinical studies should act accordingly.
Nacionalna nadležna tijela nadležna za regulatorno nadziranje ovih kliničkih ispitivanja trebaju postupiti sukladno tome.
In addition, the European Commission requested the Agency to give its opinion, as soon as possible, as to whether provisional measures were necessary to protect public health
Osim toga, Europska komisija je zatražila mišljenje od Agencije o potrebi uvođenja privremenih mjera radi zaštite javnog zdravlja, što je prije moguće.
These cases concerned 10 females, 1 male (and 1 unknown), aged between 30 and 69 years-old; 9 cases occurred in Germany, 2 in USA and 1 in Spain.
Ovi slučajevi odnose se na 10 ženskih osoba, 1 mušku osobu (i 1 nepoznatu), u dobi od 30 do 69 godina; 9 slučajeva se dogodilo u Njemačkoj, 2 u SAD-u i 1 u Španjolskoj.
The postmarketing exposure in the European Economic Area (EEA) is estimated at 3,290 patients (of which around 2,890 patients in Germany) and worldwide at 5,086 patients.
Izloženost u Europskom gospodarskom prostoru (EEA) nakon izdavanja odobrenja procjenjuje se na 3 290 bolesnika (od kojih oko 2 890 u Njemačkoj) i 5 086 bolesnika širom svijeta.
Zinbryta (daclizumab beta) has been authorised in the European Union (EU) since 1 July 2016.
Lijek Zinbryta (daklizumab beta) odobren je u Europskoj uniji (EU) od 1. srpnja 2016.
As of November 2017, 2,251 patients had received Zinbryta in the clinical development program.
Od studenoga 2017. 2 251 bolesnik primio je lijek Zinbryta u programu kliničkog razvoja.
This adverse reaction appears unpredictable and no measure to minimize the risk has been identified at this stage.
Ova se nuspojava pojavljuje nepredvidivo i u ovoj fazi još nije utvrđena mjera minimizacije rizika.
All cases were spontaneous reports, except for the Spanish case which came from an extension of a clinical trial.
Svi slučajevi bili su spontane prijave, osim španjolskih slučajeva koji su utvrđeni proširenjem kliničkog ispitivanja.
The MAH plans to terminate the study as a result of the product suspension in the EU.
Nositelj odobrenja za stavljanje u promet planira prekinuti ispitivanje kao rezultat obustave proizvoda u EU-u.
The PRAC considered the alternative treatment options for the different stages or manifestations of the disease.
PRAC je razmotrio mogućnosti alternativnog liječenja za različite faze ili očitovanja bolesti.
It was initially indicated in adult patients for the treatment of relapsing forms of multiple sclerosis (RMS).
Inicijalno je indiciran u odraslih bolesnika za liječenje relapsnih oblika multiple skleroze (RMS).
Due to the conclusion of the previous referral and based on the clinical characteristics of the patients, the MAH has already decided in January 2018 to stop this trial by 30 March 2018;
Zbog zaključenja prethodnog arbitražnog postupka i na temelju kliničkih značajki bolesnika, nositelj odobrenja za stavljanje u promet je već u siječnju 2018. odlučio zaustaviti ovo ispitivanje do 30. ožujka 2018.
These cases are characterized by torpid progression and potentially fatal or disabling outcome.
Ove slučajeve obilježava torpidna progresija i potencijalno smrtni ishod ili onesposobljenost.
SUSTAIN: A phase 3b open label study to assess efficacy and safety of daclizumab beta in patients switching from natalizumab in 5 countries, 3 in EU (DE, IT and UK).
SUSTAIN: Otvoreno ispitivanje 3b faze za procjene učinkovitosti i sigurnosti daklizumaba beta u bolesnika koji prelaze s natalizumaba u pet zemalja, tri u EU-u (DE, IT i UK).
Patients stopping treatment must be followed up for at least 6 months, as symptoms may appear after discontinuation of Zinbryta treatment.
Bolesnike koji prekidaju liječenje potrebno je pratiti najmanje 6 mjeseci, jer se simptomi mogu pojaviti nakon prekida liječenja lijekom Zinbryta.
EXTEND: extension study to assess efficacy and safety in patients from the pivotal studies.
EXTEND: nastavak ispitivanja radi procjene učinkovitosti i sigurnosti u bolesnika iz glavnih ispitivanja.
The number of doses received before the event was reported in all but two cases; it ranged between 1 and 8 doses, except for the Spanish patient who had received daclizumab beta for 4 years.
Broj primljenih doza prije događaja prijavljen je u svim slučajevima, osim dva; kretao se između i 1 i 8 doza, osim u slučaju španjolskog bolesnika koji je 4 godine primao daklizumab beta.
Further to that on 22 February, PEI informed about 2 new cases of immunemediated disease with CNS involvement.
Nakon toga, 22. veljače, PEI je izvijestio o dvama novim slučajevima imunološki posredovane bolesti koja obuhvaća SŽS.
The PRAC discussed the possibility of the causal relationship of these adverse reactions, as well as the possible mechanism through which they could have been triggered.
PRAC je raspravljao o mogućnosti uzročne povezanosti ovih nuspojava, kao i mogućeg mehanizma kojim su mogle biti potaknute.
Four of the five patients experienced also fever, leukocytosis, exanthema/skin reactions, thus potentially meeting the criteria for DRESS.
Četiri od pet bolesnika također je imalo groznicu, leukocitozu, eksantemu / kožne reakcije, čime su potencijalno ispunjavali kriterije za DRESS.
On 26 February 2018, pursuant to Article 20 of Regulation (EC) No 726/2004, the European Commission requested the opinion of the Agency on whether the marketing authorisation of Zinbryta should be maintained, varied, suspended or revoked.
Uredbe (EZ) br. 726/2004, Europska komisija je 26. veljače 2018. zatražila mišljenje Agencije o tome treba li odobrenje za stavljanje lijeka Zinbryta u promet zadržati, izmijeniti, obustaviti ili povući.
From the third PSUR (period from 27 May 2017 - 26 November 2017), there have also been some cases of unexpected deaths, attributed to cerebrovascular accidents, but with no detailed information on them that would conclusive allow for the exclusion of encephalitis.
Od trećeg PSUR-a (razdoblje od 27. svibnja 2017. do 26. studenog 2017.) također je bilo neočekivanih smrtnih slučajeva, koji se mogu pripisati cerebrovaskularnim nesrećama, ali bez detaljnih podataka o njima koji bi omogućili definitivno isključenje encefalitisa.
Three of these cases had a fatal outcome, 2 cases are still intubated, 1 has an Expanded Disability Status Scale (EDSS) score 9.5, 1 recovered with sequelae, 1 partially recovered, and the remaining cases had an unknown outcome.
Tri od ovih slučajeva imali su smrtni ishod, dva slučaja još su uvijek intubirana, jedan ima ocjenu 9,5 na proširenoj ocjenskoj ljestvici onesposobljenosti (EDSS), jedan je oporavljen sa sekvelom, jedan je djelomično oporavljen, a preostali slučajevi imali su nepoznat ishod.
In addition, no new patients should start treatment with Zinbryta.
Osim toga, ne smije se započinjati liječenje novih bolesnika lijekom Zinbryta.
The use and the marketing authorisation for Zinbryta should be suspended and the product should be recalled from the market at the level of pharmacies and hospitals.
Potrebno je obustaviti uporabu i odobrenje za stavljanje u promet za lijek Zinbryta, a proizvod je potrebno opozvati s tržišta na razini ljekarni i bolnica.
Immune-mediated or autoimmune conditions such as type I diabetes, colitis, autoimmune thyroiditis, pancreatitis, glomerulonephritis, among other, were reported in low numbers.
Imunološki posredovana ili autoimuna stanja, kao što su dijabetes tipa I, kolitis, autoimuni tireoiditis, pankreatitis, glomerulonefritis, između ostalih, prijavljeni su u malom broju slučajeva.
At least 5 of these patients had clinical symptoms compatible with ‘drug rash with eosinophilia and systemic symptoms' (DRESS) syndrome, one of which was confirmed with skin biopsy and one highly suspected.
Najmanje 5 od ovih bolesnika imalo je kliničke simptome kompatibilne sa sindromom „reakcije na lijekove s eozinofilijom i sistemskim simptomima” (DRESS), od kojih je jedan potvrđen biopsijom kože, a za jedan je postojala velika sumnja.
It was acknowledged that the mechanism of action of daclizumab beta is complex.
Poznato je da je mehanizam djelovanja daklizumaba beta složen.
Activation and expansion of NK cells may lead to a higher cytotoxic response that may be involved in the pathogenesis of autoimmune hepatitis and other autoimmune diseases.
Aktivacija i ekspanzija NK stanica može dovesti do veće citotoksične reakcije, koja može biti obuhvaćena u patogenezi autoimunog hepatitisa i drugih autoimunih bolesti.
Healthcare professionals should contact patients currently being treated with Zinbryta and should stop their treatment and consider alternatives as a matter of urgency.
Zdravstveni radnici trebaju kontaktirati bolesnike koji se trenutačno liječe lijekom Zinbryta i prekinuti njihovo liječenje te hitno razmotriti alternative.
Furthermore, the analysis of PSUR data indicated that a range of immune-mediated disorders were reported in other organs than the brain and liver following the use of Zinbryta.
Nadalje, analiza podataka PSUR-a upućuje da je prijavljen niz imunološki posredovanih poremećaja kod drugih organa, osim mozga i jetre, nakon uporabe lijeka Zinbryta.
• In view of the above, the PRAC considered that the benefit-risk balance of Zinbryta is no longer favourable and that urgent measures are needed to protect patients.
• S obzirom na prethodno navedeno, PRAC je smatrao da omjer koristi i rizika za lijek Zinbryta više nije povoljan i da su potrebne hitne mjere radi zaštite bolesnika.
Although the absolute number of the individual reports for each disorder was low, cumulatively there were a significant number of autoimmune events possibly related to daclizumab beta treatment.
Iako je apsolutni broj pojedinačnih prijava za svaki poremećaj bio mali, kumulativno je postojao značajan broj autoimunih događaja koji mogu biti povezani s liječenjem daklizumabom beta.
It is plausible that the immunomodulatory effects of the drug are involved in immune-mediated adverse effects, such as autoimmune hepatitis, and could be related to the reported cases of encephalitis and/or meningoencephalitis.
Moguće je da su imunomodulatorni učinci lijeka obuhvaćeni u imunološki posredovanim štetnim učincima, kao što je autoimuni hepatitis, a mogu biti povezani s prijavljenim slučajevima encefalitisa ili meningoencefalitisa.
A PRAC review concluded on 31 October 2017 (due to cases of immune-mediated liver injury) led to the restriction of indication to the treatment of adult patients with relapsing forms of multiple sclerosis who have had an inadequate response to at least two disease modifying therapies (DMTs) and for whom treatment with any other DMT is contraindicated or otherwise unsuitable.
Zaključak PRAC-a nakon pregleda 31. listopada 2017. (zbog slučajeva imunološki posredovanih ozljeda jetre) doveo je do ograničenja indikacije za liječenje odraslih bolesnika s relapsnim oblicima multiple skleroze koji nisu adekvatno reagirali na barem dvije terapije koje modificiraju tijek bolesti (DMT) i kod kojih je liječenje bilo kojim drugim DMT-om kontraindicirano ili neodgovarajuće iz drugih razloga.
In summary, 12 cases of serious and potentially fatal immune-mediated events involving CNS, with symptoms initially compatible with relapse of MS and later on explained by unexpected findings in the neuropathology, with a predominantly inflammatory process and eosinophilic granulocytes, were reported.
Ukratko, prijavljeno je 12 slučajeva ozbiljnih i potencijalno smrtonosnih imunološki posredovanih događaja koji obuhvaćaju SŽS, sa simptomima koji su u početku kompatibilni sa relapsom MS-a, a kasnije objašnjeni neočekivanim nalazima u neuropatologiji, s dominantno upalnim procesom i eozinofilnim granulocitima.
• The PRAC reviewed the totality of the available data, including data provided by the marketing authorisation holder in writing and in an oral explanation on the 12 cases of serious encephalitis and meningo-encephalitis (of which three fatal) reported since the initial marketing authorisation and safety data from clinical trials, in relation to the overall risk of immune-mediated disorders with CNS involvement during treatment with Zinbryta.
• PRAC je pregledao sve dostupne podatke, uključujući podatke koje je dostavio nositelj odobrenja za stavljanje u promet u pisanom obliku i uz usmeno objašnjenje o 12 slučajeva ozbiljnog encefalitisa i meningoencefalitisa (od kojih tri sa smrtonosnim ishodom) prijavljena od početka odobrenja za stavljanje u promet te sigurnosne podatke iz kliničkih ispitivanja, u vezi s cjelokupnim rizikom od imunološki posredovanih poremećaja koji obuhvaćaju SŽS tijekom liječenja lijekom Zinbryta.
Further, the PRAC took into consideration that interrupting treatment in patients whose disease is well-controlled with daclizumab beta may induce relapses, but considered that the serious risk of auto-immune or immune-mediated reactions outweighs the benefit that daclizumab beta may bring to relapsed patients eligible to the authorised indication.
Nadalje, PRAC je uzeo u obzir da prekidanje liječenja u bolesnika čija je bolest pod nadzorom uzimanjem daklizumaba beta može izazvati relapse, ali je smatrao da ozbiljan rizik od autoimunih ili imunološki posredovanih reakcija nadmašuje korist koju daklizumab beta može donijeti bolesnicima s relapsom koji ispunjavaju odobrenu indikaciju.
In the second PSUR (period from 27 November 2016 - 26 May 2017), the review of autoimmune encephalitis cases and other immune-related disorders cases showed that there was a wide variety of immune-mediated disorders reported (such as encompassed seronegative arthritis, blood dyscrasias, thyroid disorders, glomerulonephritis and skin and subcutaneous disorders).
U drugom izvješću o neškodljivosti lijeka (PSUR) (razdoblje od 27. studenog 2016. do 26. svibnja 2017.) pregled slučajeva autoimunog encefalitisa i drugih slučajeva poremećaja povezanih s imunološkim sustavom pokazao je da je bilo prijavljeno mnoštvo imunološki posredovanih poremećaja (kao što je obuhvatni seronegativni artritis, krvna diskrazija, poremećaji štitnjače, glomerulonefritis i poremećaji kože i potkožnog tkiva).
Whilst the absolute numbers for each disorder is low, this raises concerns that these disorders could be induced by immune-mediated effects and could be causally associated with Zinbryta.
Iako su apsolutni brojevi za svaki poremećaj mali, pojavljuje se zabrinutost da su ovi poremećaji mogli biti potaknuti imunološki posredovanim učincima i mogu se uzročno povezati s lijekom Zinbryta.
• Furthermore, PRAC recommended that a healthcare professional communication should be disseminated to inform healthcare professionals about the risks related to Zinbryta and provide instructions related to the cessation of the treatment and the follow-up of patients having received Zinbryta.
• Nadalje, PRAC je preporučio širenje komunikacije među zdravstvenim radnicima radi informiranja zdravstvenih radnika o rizicima povezanim s lijekom Zinbryta i davanje uputa u vezi s prestankom liječenja i praćenja bolesnika koji su primali lijek Zinbryta.
Together, these immunomodulatory effects of daclizumab beta are believed to reduce central nervous system (CNS) pathology in MS and thereby reduce the occurrence of relapses and disability progression.
Smatra se da ovi imunomodulirajući učinci daklizumaba beta zajedno smanjuju patologiju središnjeg živčanog sustava (SŽS) u MS-u te time smanjuju pojavu relapsa i napredovanja onesposobljenosti.
On 20 February 2018, the Paul Ehrlich Institute (PEI) informed the EMA about five patients who were treated in 2016 and 2017 with daclizumab beta in Germany, and experienced worsening of disease after initiation of therapy.
EMA-u o petero bolesnika koji su liječeni daklizumabom beta 2016. i 2017. u Njemačkoj, a kod kojih je nakon početka liječenja došlo do pogoršanja bolesti.
Overall, 12 cases of encephalitis or encephalopathy in patients treated with daclizumab beta for multiple sclerosis have been identified.
Sveukupno je utvrđeno 12 slučajeva encefalitisa ili encefalopatije u bolesnika liječenih daklizumabom beta zbog multiple skleroze.
In view of the seriousness of the reactions reported and the biological plausibility, the risk of immunemediated encephalitis and its impact on the benefit-risk balance of the medicinal product should be investigated, as well as the adequacy of the risk minimization measures with regard to immunemediated CNS involvement (encephalitis) need to be assessed.
S obzirom na ozbiljnost prijavljenih reakcija i biološku plauzibilnost, potrebno je istražiti rizik od imunološki posredovanog encefalitisa i njegova učinka na omjer koristi i rizika lijeka, a potrebno je procijeniti i adekvatnost mjera minimizacije rizika koje se odnose na imunološki posredovano obuhvaćanje SŽS-a (encefalitis).
• In addition, PRAC also considered the known serious immune-mediated liver toxicity associated with Zinbryta as well as potential other immune-mediated disorders affecting other organs than the brain or the liver.
• Osim toga, PRAC je također razmotrio poznatu ozbiljnu imunološki posredovanu toksičnost jetre povezanu s lijekom Zinbryta, kao i potencijalne ostale imunološki posredovane poremećaje kod drugih organa, osim mozga i jetre.
Key effects of this IL-2 pathway modulation potentially related to the therapeutic effects of daclizumab beta in multiple sclerosis (MS) include selective antagonism of activated T-cell responses, and expansion of immunoregulatory CD56bright natural killer (NK) cells, which have been shown to selectively decrease activated T-cells.
Ključni učinci ove modulacije signalnog puta IL-2 potencijalno povezani s terapijskim učincima daklizumaba beta u multiploj sklerozi (MS) uključuju selektivni antagonizam odgovora aktiviranih T-stanica i ekspanziju imunoregulatornih CD56bright stanica prirodnih ubojica (NK), za koje je utvrđeno da selektivno smanjuju broj aktiviranih T-stanica.
In light of all of the above and having carefully assessed all available data, PRAC considered at this stage that the benefit-risk balance of the product is no longer favourable and that urgent measures in accordance with Article 20(3) of Regulation (EC) No 726/2004, taking into account the grounds set out in Articles 116 and 117 of Directive 2001/83/EC, are needed to protect patients.
S obzirom na sve prethodno navedeno i nakon pažljive procjene svih dostupnih podataka, PRAC je u ovoj fazi smatrao da omjer koristi i rizika proizvoda više nije povoljan i da su potrebne hitne mjere u skladu s člankom 20. stavkom 3. Uredbe (EZ) br. 726/2004, uzimajući u obzir osnove utvrđene u člancima 116. i 117.
Daclizumab beta blocks CD25 (alfa subunit of high affinity IL-2 receptor), decreasing the number and function of CD4+CD25+FoxP3+Treg and produces an activation and expansion of CD56 NK cells.
Daklizumab beta blokira CD25 (alfa-subunit IL-2 receptora visokog afiniteta), smanjujući broj i funkciju CD4+CD25+FoxP3+Treg i proizvodi aktivaciju i ekspanziju CD56 NK stanica.
PRAC has considered carefully the above described cases, the probable mechanism of action for these adverse events, along with the potential for auto-immune or immune-mediated reactions that appears associated with Zinbryta, the product mechanism of action, the biological plausibility, and that no risk minimisation measures (RMMs) can be foreseeable to prevent occurrence of these risks in patients on treatment with daclizumab beta at this stage.
PRAC je pažljivo razmotrio prethodno opisane slučajeve, mogući mehanizam djelovanja za ove nuspojave, zajedno s mogućnošću autoimunih i imunološki posredovanih reakcija koje se pojavljuju u vezi s lijekom Zinbryta, mehanizam djelovanja proizvoda, biološku plauzibilnost, te da mjere minimizacije rizika (RMMs) ne mogu biti predvidive radi sprečavanja pojave ovih rizika u bolesnika koji se liječe daklizumabom beta u ovoj fazi.
PRAC concluded that these adverse reactions could be causally associated with Zinbryta.
PRAC je zaključio da ove nuspojave mogu biti uzročno povezane s lijekom Zinbryta.
• The PRAC considered the procedure under Article 20 of Regulation (EC) No 726/2004 resulting from pharmacovigilance data for Zinbryta, in particular the need for provisional measures in accordance with Article 20(3) of Regulation (EC) No 726/2004, taking into account the grounds set out in Articles 116 and 117 of Directive 2001/83/EC.
Uredbe (EZ) br. 726/2004 koji je proizašao iz podataka o farmakovigilanciji za lijek Zinbryta, posebno u pogledu potrebe donošenja privremenih mjera u skladu s člankom 20. stavkom 3. Uredbe (EZ) br. 726/2004, uzimajući u obzir osnove utvrđene u člancima 116. i 117.
Autoimmune haemolytic anemia is already known to be related to daclizumab beta treatment.
Već je poznato da je autoimuna hemolitička anemija povezana s liječenjem daklizumabom beta.
Daclizumab beta is hypothesized to exert its activity in MS through immunomodulatory mechanisms.
Za daklizumab beta pretpostavlja se da djeluje na MS kroz imunomodulatorne mehanizme.
It was noted that there are ongoing clinical studies for which the MAH informed PRAC that the treatment with daclizumab beta is to be stopped.
Navedeno je da se provode klinička ispitivanja za koja je nositelj odobrenja za stavljanje u promet izvijestio PRAC da je potrebno prekinuti liječenje daklizumabom beta.
Administration of acute corticosteroids and/or plasmapheresis did not improve the clinical situation, brain biopsies were obtained, which showed an unexpected finding of massive inflammation with eosinophilic granulocytes (unexpected in MS patients).
Primjena akutnih kortikosteroida ili plazmafereze nije poboljšala kliničku situaciju, provedene su biopsije mozga, koje su pokazale neočekivani nalaz jake upale s eozinofilnim granulocitima (neočekivano kod bolesnika s MS-om).
Daclizumab beta is a humanised IgG1 monoclonal antibody that modulates IL-2 signalling by blocking CD25-dependent, high affinity IL-2 receptor signalling, resulting in higher levels of IL-2 available for signalling through the intermediate-affinity IL-2 receptor.
Daklizumab beta je humanizirano IgG1 monoklonalno antitijelo koje modulira signaliziranje IL-2 blokiranjem signaliziranja putem IL-2 receptora visokog afiniteta ovisnog o CD25, što dovodi do viših razina IL-2 na raspolaganju za signaliziranje putem IL-2 receptora intermedijarnog afiniteta.
• The PRAC recommended to suspend the use and the marketing authorisation for Zinbryta, and to recall all the batches of the medicinal product from the market up to the level of pharmacies and hospitals.
• PRAC je preporučio obustavu uporabe i odobrenja za stavljanje u promet za lijek Zinbryta te opoziv svih serija lijeka s tržišta do razine ljekarni i bolnica.
Some of these patients did not improve despite treatment with corticosteroids and/or plasmapheresis in these patients brain biopsies were obtained, which showed an unexpected finding of massive inflammation with eosinophilic granulocytes.
Kod nekih od ovih bolesnika nije došlo do poboljšanja unatoč liječenju kortikosteroidima ili plasmafereza je provedena u biopsijama mozga ovih bolesnika, koja je pokazala neočekivani nalaz jake upale s eozinofilnim granulocitima.
Daclizumab beta binds to the alpha-subunit (CD25) of the high-affinity interleukin-2 (IL-2) receptor.
Daklizumab beta se veže na alfa-subunit (CD25) receptora interleukina-2 (IL-2) visokog afiniteta.
More information concerning these immune-mediated events had been requested to the MAH to be submitted in the third PSUR.
Od nositelja odobrenja za stavljanje u promet zatraženo je da u trećem PSUR-u dostavi više informacija koje se odnose na ove imunološki posredovane događaje.
Grounds for PRAC recommendation
Razlozi za preporuku PRAC-a Budući da: