FrancophonIA/ELRC3.0 huggingface dataset:
English: Some of the cases identified with DAAs had serious outcomes, with worsening of hepatic status and at least one case where the patient required liver transplantation.
Danish: Nogle af de tilfælde, der blev identificeret med DAA'er, havde alvorlige konsekvenser med forværring af leverstatus og mindst ét tilfælde, hvor patienten måtte indstilles til levertransplantation.
English: CHMP opinion and detailed explanation of the scientific grounds for the differences from the PRAC recommendation
Danish: CHMP's udtalelse og detaljerede redegørelse for den videnskabelige begrundelse for afvigelserne fra PRAC's anbefaling
English: The product information will include a warning to inform about the risk of hepatitis B reactivation and reflect these recommendations.
Danish: Produktinformationen vil inkludere en advarsel om, at informere om risikoen for hepatitis B-reaktivering og vil afspejle disse anbefalinger.
English: The RMP should be updated accordingly within 3 months of this CHMP opinion.
Danish: Risikostyringsplanen skal opdateres i overensstemmelse hermed inden for 3 måneder af denne CHMPudtalelse.
English: In addition, ‘patients with previous HCC' should be considered as missing information, since this population was excluded from available clinical trials.
Danish: Derudover skal "patienter med tidligere HCC" betragtes som manglende oplysninger, da denne patientgruppe blev udelukket fra tilgængelige kliniske forsøg.
English: Direct-acting antiviral agents (DAAs) target specific non-structural proteins of the hepatitis C virus and result in disruption of viral replication and infection.
Danish: Direkte aktive antivirale lægemidler (DAA'er) er rettet mod specifikke non-strukturelle proteiner i hepatitis C-virus og resulterer i hæmning af viral replikation og infektion.
English: As both requests for the triggered procedure result from the evaluation of data resulting from pharmacovigilance activities, the EC requested the opinion to be adopted by the Committee for Medicinal Products for Human Use (CHMP) on the basis of a recommendation of the Pharmacovigilance Risk Assessment Committee (PRAC).
Danish: Da begge anmodninger for den påbegyndte procedure bunder i en gennemgang af data fra lægemiddelovervågningsaktiviteter, har Kommissionen udbedt sig, at udtalelsen vedtages af Udvalget for Lægemidler til Mennesker (CHMP) på grundlag af en anbefaling fra Udvalget for Risikovurdering inden for Lægemiddelovervågning (PRAC).
English: Patients with HBV/HCV co-infection should be monitored during and after treatment according to current clinical guidelines.
Danish: Patienter med HBV/HCV coinfektion skal monitoreres under og efter behandlingen i henhold til gældende kliniske retningslinjer.
English: Therefore data on HBV reactivation with DAAs mostly arose post-marketing.
Danish: Derfor fremkom data om HBVreaktivering med DAA'er overvejende efter markedsføringen.
English: The virological and immunological aspects of HBV/HCV co-infection are not fully comprehended.
Danish: De virologiske og immunologiske aspekter af HBV/HCV co-infektion er ikke fuldt afklaret.
English: It may be assumed however that patients with more advanced liver disease may have a higher risk of severe clinical complications should HBV reactivation occur.
Danish: Det kan dog antages, at patienter, hvis leversygdom er mere fremskreden, kan have højere risiko for alvorlige kliniske komplikationer, hvis HBV-reaktivering skulle forekomme.
English: It was considered that in addition to the hepatitis B virus reactivation, the risk of hepatocellular carcinoma should also be further investigated and that consideration should be given for adequate measures to optimise the safe and effective use of these medicinal products.
Danish: Man fandt, at, udover reaktivering af hepatitis B-virus, burde risikoen for hepatocellulært carcinom ligeledes undersøges nærmere og at passende foranstaltninger til optimering af sikker og effektiv anvendelse af disse lægemidler burde overvejes.
English: The PRAC was of the view that all patients should be screened for hepatitis B virus infection before initiation of treatment with DAAs.
Danish: PRAC var af den opfattelse, at alle patienter skal screenes for hepatitis B-virus-infektion inden behandlingsstart med DAA'er.
English: The European Association for the Study of the Liver (EASL) recommendations on treatment of hepatitis C makes reference to the potential risk of HBV reactivation during or after HCV clearance.
Danish: I anbefalingerne fra The European Association for the Study of the Liver (EASL) om behandling af hepatitis C bliver der gjort opmærksom på den potentielle risiko for HBV-reaktivering under eller efter HCV-clearance.
English: • The PRAC considered the procedure under Article 20 of Regulation (EC) No 726/2004 resulting from pharmacovigilance data for direct-acting antiviral agents (DAAs) indicated in the treatment chronic hepatitis C.
Danish: • PRAC fandt, at proceduren i henhold til artikel 20 i forordning (EF) nr. 726/2004, der var foranlediget af lægemiddelovervågningsdata om direkte aktive antivirale lægemidler (DAA'er) indiceret til behandling af kronisk hepatitis C.
English: The European Commission therefore extended the scope of the procedure in April 2016 to allow consideration of other data to assess the risk of hepatocellular carcinoma and its impact on the benefit-risk balance for all DAAs in the treatment of chronic hepatitis C.
Danish: Europa-Kommissionen udvidede derfor omfanget af proceduren i april 2016 af hensyntagen til andre data til vurdering risikoen for hepatocellulært carcinom og carcinomets indvirkning på benefit/risk-forholdet for alle DAA'er i behandlingen af kronisk hepatitis C.
English: However, these cohorts were either not designed for assessing HCC recurrence, as is the case of the ANRS CO22 HEPATHER cohort, or included a limited number of patients with a previous HCC reaching complete radiological response and subsequently treated with DAAs as in the ANRS CO12 CirVir cohort.
Danish: Disse kohorter var dog ikke sammensat med henblik på vurdering af HCC-recidiv, som tilfældet er med ANRS CO22 HEPATHER-kohorten, eller inkluderede et begrænset antal patienter med et tidligere HCC, hvor patienten opnåede fuldstændigt radiologisk respons og derefter blev behandlet med DAA'er som i ANRS CO12 CirVir-kohorten.
English: Although severe and even fatal cases of HBV reactivation have been described in the literature, the available data indicate that reactivation of HBV replication may mostly be mild and without clinical consequences.
Danish: Selvom der er beskrevet alvorlige og endog fatale tilfælde af HBV-reaktivering i litteraturen, indikerer tilgængelige data, at reaktiveringen af HBV-replikation i de fleste tilfælde er mild og uden kliniske konsekvenser.
English: Literature cases (Balagopal et al., 2015; Collins et al., 2015; Ende et al., 2015) described HBV viral load increase after a rapid decline of HCV viral load in patients treated with direct acting antivirals (DAA) in interferon-free regimens, and further cases have been identified in EudraVigilance.
Danish: I tilfælde taget fra litteraturen (Balagopal et al., 2015, Collins et al., 2015 og Ende et al., 2015) beskrives der en stigning i HBV-virusbyrden efter et hurtigt fald i HCV-virusbyrden hos patienter behandlet med direkte aktive antivirale lægemidler (DAA'er) i behandlinger uden interferon, og der er derudover identificeret tilfælde i EudraVigilance.
English: The PRAC was also of the view that ‘emergence of hepatocellular carcinoma' and ‘recurrence of hepatocellular carcinoma' should be considered as important potential risks.
Danish: PRAC mener ligeledes at "opståen af hepatocellulært carcinom" og "recidiv af hepatocellulært carcinom" bør betragtes som vigtige potentielle risici.
English: The research should capture prospectively the known risk factors for HCC and the periodic image testing for HCC diagnosis, according to current European clinical guidelines (EASL).
Danish: Forskningen skal prospektivt registrere kendte risikofaktorer for HCC og regelmæssige billedundersøgelser med henblik på HCC-diagnose i henhold til de aktuelle kliniske retningslinjer fra EASL.
English: The current referral procedure was triggered by the European Commission (EC) to allow further investigation of the risk of hepatitis B virus replication after starting treatment with DAAs and recommend any appropriate measure to minimise the risk.
Danish: Den aktuelle procedure for indbringelse af sager blev iværksat af Europa-Kommissionen for at muliggøre en nærmere undersøgelse af risikoen for hepatitis B-virus-replikation efter behandlingsstart med DAA'er og anbefale eventuelle relevante risikominimerende tiltag.
English: Hepatitis В virus (HBV) and hepatitis C virus (HCV) co-infection is not uncommon due to overlapping transmission modes.
Danish: Co-infektion med hepatitis В-virus (HBV) og hepatitis C-virus (HCV) er ikke ualmindeligt grundet de overlappende smitteveje.
English: A feasibility assessment of the use of existing data sources for this purpose should be submitted for PRAC assessment by 15 June 2017.
Danish: Der skal til dette formål indsendes en forundersøgelse om brugen af eksisterende datakilder til PRAC's evaluering senest 15. juni 2017.
English: Given their increased potency against HCV and lack of anti-HBV activity, the risk of HBV reactivation may be greater with newer HCV treatment regimens than with the previously approved interferon-based HCV treatments.
Danish: Grundet deres øgede styrke over for HCV og manglende anti-HBV-aktivitet kan risikoen for HBV-reaktivering være større ved nyere HCV-behandlinger end ved de tidligere godkendte interferon-baserede HCV-behandlinger.
English: Although liver disease activity and progression are generally more severe in the presence of double infection, HBV replication is often suppressed in the presence of HCV coinfection.
Danish: Selvom aktiviteten og progressionen i leversygdom generelt er mere alvorlig ved dobbeltinfektion, hæmmes HBV-replikationen ofte ved HCV co-infektion.
English: Generally, the reactivation occurred shortly after the initiation of treatment in a pattern that implies a correlation with the rapid decrease in HCV viral load which characterises the viral load dynamics with DAAs.
Danish: Reaktiveringen forekom generelt kort tid efter behandlingsstart i et mønster, der antyder en forbindelse med det hurtige fald i HCV-virusbyrden, som karakteriserer virusbyrdens dynamik med DAA'er.
English: After further consideration of the timelines proposed for the submission of the final study report and taking into account that the protocol is due to be submitted by 15 June 2017, the CHMP was of the opinion that the date for the submission of the final study report should be postponed to Q2 2021 in order to allow sufficient time for agreement on a joint protocol and for collection of sufficient data to adequately respond to the scientific question.
Danish: Efter yderligere overvejelser hvad angår de foreslåede tidsfrister for indsendelsen af den endelige undersøgelsesrapport og under hensyntagen til, at protokollen skal indsendes senest 15. juni 2017, fandt CHMP, at datoen for indsendelsen af den endelige undersøgelsesrapport skal udsættes til andet kvartal af 2021.
English: The protocol of this study shall be submitted to the PRAC by 15 June 2017 and the final study results by Q4 2019.
Danish: Protokollen for denne undersøgelse skal indsendes til PRAC senest 15. juni 2017 og undersøgelsens endelige resultater skal indsendes senest i fjerde kvartal af 2019.
English: With regards to the review of HCC with DAAs, MAHs were requested to perform a comprehensive review of all available data from clinical trials, observational studies, spontaneous reports and published literature on HCC in patients with chronic hepatitis C after treatment with DAAs.
Danish: Med hensyn til gennemgangen af HCC med DAA'er, blev indehaverne af markedsføringstilladelserne bedt om at gennemføre en grundig gennemgang af alle tilgængelige data fra kliniske forøg, observationsundersøgelser, spontane rapporter og offentliggjort litteratur om HCC hos patienter med kronisk hepatitis C efter behandling med DAA'er.
English: Overall, the PRAC considered that further studies were warranted to further characterise the risk of HCC recurrence associated with DAAs, in order to address remaining uncertainties about this potential risk and conclude on the need for any additional advice on clinical management.
Danish: Samlet set vurderede PRAC, at der var brug for flere undersøgelser for yderligere at kunne karakterisere risikoen for HCC-recidiv i forbindelse med DAA'er for derved at kunne afklare øvrige usikkerhedsmomenter omkring den potentielle risiko og for at kunne drage en konklusion om behovet for eventuel supplerende vejledning omkring klinisk behandling.
English: • The PRAC was also of the opinion that the impact of DAAs treatment on the incidence and type of de novo hepatocellular carcinoma should be further investigated though a prospective cohort study in HCV infected patients with cirrhosis.
Danish: • PRAC var også af den opfattelse, at virkningen af DAA-behandling på incidensen og typen af de novo hepatocellulært carcinom skal undersøges yderligere gennem en prospektiv kohorte undersøgelse hos HCV-inficerede patienter med cirrose.
English: HBV replication after starting treatment with DAAs for HCV infection is not currently described in the product information of currently authorised products and in view of the seriousness of the events described, the need for intervention on HBV replication and the biological plausibility of the replication it was considered that further investigation was warranted.
Danish: HBV-replikation efter behandlingsstart med DAA'er for HCV-infektion er i øjeblikket ikke beskrevet i produktinformationen for eksisterende godkendte lægemidler og på grund af de alvorlige hændelser, der er beskrevet, behovet for intervention for HBV-replikation og den biologiske sandsynlighed for replikationen, blev det konkluderet, at en nærmere undersøgelse var berettiget.
English: In addition, interim results should be submitted for PRAC assessment by Q4 2019.
Danish: Der skal derudover indsendes foreløbige resultater til PRAC's vurdering senest i fjerde kvartal af 2019.
English: HCV infection is known to cause suppression of HBV replication in co-infected patients.
Danish: HCV-infektion vides at forårsage hæmning af HBV-replikation hos coinficerede patienter.
English: Based on the findings of Reig et al, concerns on the development of de novo HCC in cirrhotic HCV patients treated with DAA were also raised, as these patients may harbour not yet diagnosed HCC.
Danish: Der blev på baggrund af resultaterne fra Reig et al også rejst betænkelighed ved udviklingen af de novo HCC hos cirrotiske HCV-patienter behandlet med DAA, da disse patienter kan have HCC, der ikke er diagnosticeret endnu.
English: • Concerning the risk of recurrence of HCC in patients using DAAs, the PRAC considered that further data are required on the impact of DAAs treatment on the incidence of HCC recurrence.
Danish: • Hvad angår risikoen for HCC-recidiv hos patienter, der bruger DAA'er, fandt PRAC, at der er behov for flere oplysninger om virkningen af behandling med DAA'er på incidensen af HCCrecidiv.
English: Following the initiation of this review, results from a study (Reig et al. 2016) performed between October 2014 and December 2015 in Hepatology Units of four University Spanish hospitals in patients with chronic hepatitis C and a history of hepatocellular carcinoma (HCC) treated with DAAs suggested unexpected early HCC recurrence.
Danish: 2016), der blev gennemført i perioden oktober 2014 til december 2015 på hepatologiafdelinger på fire spanske universitetshospitaler hos patienter med kronisk hepatitis C, og hvis anamnese inkluderede hepatocellulært carcinom (HCC), og som var behandlet med DAA'er, et uventet, tidligt recidiv af HCC.
English: In order to minimise the risk of HBV reactivation, the PRAC recommended that all patients should be screened for HBV infection before initiation of treatment with DAAs and that patients presenting a coinfection HBV/HCV should be monitored and managed according to current clinical guidelines.
Danish: For a minimere risikoen for HBV-reaktivering anbefalede PRAC, at alle patienter screenes for HBVinfektion inden behandlingsstart med DAA'er, og at patienter med HBV/HVC co-infektion monitoreres og behandles i henhold til de aktuelle kliniske retningslinjer.
English: The impact of chronic HCV infection characteristics, such as HCV genotype, viral load and histopathologic staging, on the risk of occurrence of HBV reactivation could not be clarified from the available data.
Danish: Betydningen af karakteristikaene ved kronisk HCV-infektion, som f.eks. HCV-genotype, virusbyrde og histopatologisk stadieinddeling, for risikoen for forekomsten af HBV-reaktivering kunne ikke afklares ud fra de tilgængelige data.
English: • The PRAC reviewed the totality of the data submitted in writing and during the oral explanations by the marketing authorisation holders in relation to the risk of hepatitis B reactivation and to the concerns raised following reports of hepatocellular carcinoma in patients using DAAs, as well as the outcome of the meeting of the scientific advisory group on HIV/Viral diseases.
Danish: • PRAC gennemgik alle indsendte skriftlige data og mundtlige forklaringer fra indehaverne af markedsføringstilladelserne med hensyn til risikoen for hepatitis B-reaktivering og de betænkeligheder dette gav anledning til efter rapporter om hepatocellulært carcinom hos patienter, der bruger DAA'er, samt resultaterne fra mødet, der blev afholdt af den videnskabelige rådgivende gruppe, om hiv-/virussygdomme.
English: The CHMP, as a consequence, considers that the benefit-risk balance of Daklinza, Exviera, Harvoni, Olysio, Sovaldi and Viekirax remains favourable subject to the amendments to the product information and to the conditions described above.
Danish: CHMP finder følgeligt, at benefit/risk-forholdet for Daklinza, Exviera, Harvoni, Olysio, Sovaldi og Viekirax fortsat er positivt under forudsætning af, at de nævnte ændringer indføres i produktinformationen og i henhold til ovennævnte betingelser.
English: Overall, the PRAC was of the view that evidence exists of a risk of HBV reactivation in HBV/HCV coinfected patients treated with DAAs and therefore HBV reactivation in co-infected patients should be considered as an important identified risk which should be closely monitored through routine risk minimisation activities.
Danish: PRAC fandt generelt, at der foreligger bevis for risiko for HBV-reaktivering hos HBV/HCV co-inficerede patienter behandlet med DAA'er, og at HBV-reaktivering hos co-inficerede patienter derfor skal betragtes som en vigtig, identificeret risiko, som skal monitoreres tæt gennem rutinemæssige risikominimerende aktiviteter.
English: In view of the above, the PRAC considers that the benefit-risk balance of direct-acting antivirals remains favourable subject to the amendments to the terms of the marketing authorisations.
Danish: På grundlag af ovenstående konkluderer PRAC, at benefit/risk-forholdet for direkte aktive antivirale lægemidler fortsat er positivt under forudsætning af, at de foreslåede ændringer indføres i markedsføringstilladelsen.
English: • Concerning HBV reactivation, the PRAC concluded that available data provide evidence of a risk of HBV reactivation in patients co-infected with HBV/HCV treated for chronic hepatitis C with DAAs.
Danish: • Hvad angår HBV-reaktivering konkluderede PRAC, at de tilgængelige data giver bevis for risikoen for HBV-reaktivering hos patienter co-inficeret med HBV/HCV og behandlet for kronisk hepatitis C med DAA'er.
English: Therefore the CHMP recommends the variation to the terms of the marketing authorisations for Daklinza, Exviera, Harvoni, Olysio, Sovaldi and Viekirax.
Danish: CHMP anbefaler derfor ændring af betingelserne for markedsføringstilladelserne for Daklinza, Exviera, Harvoni, Olysio, Sovaldi og Viekirax.
English: Clinical trial data on incidence of new on-set HCC show higher point estimates for HCC after reaching SVR with IFN-free regimens compared to IFN-containing regimens, also when stratifying by presence of cirrhosis.
Danish: Data fra kliniske forsøg om incidensen af nyopstået HCC viser højere punktestimater for HCC efter opnåelse af vedvarende virologisk respons med IFN-fri behandling sammenlignet med IFN-holdig behandling, også når der stratificeres ifølge forekomst af cirrose.
English: Overall summary of the scientific evaluation by the PRAC In its assessment, the PRAC considered all the data submitted by the MAHs, as well as literature and additional information from a scientific advisory group in relation to the risk of hepatitis B reactivation and to the recurrence and occurrence of hepatocellular carcinoma.
Danish: PRAC medtog i sin vurdering alle data indsendt af indehaverne af markedsføringstilladelserne, samt litteratur og yderligere oplysninger fra en videnskabelig rådgivende gruppe med hensyn til risikoen for hepatitis B-reaktivering og om recidiv og forekomst af hepatocellulært carcinom.
English: The PRAC, as a consequence, recommends the variation to the terms of the marketing authorisations for Daklinza, Exviera, Harvoni, Olysio, Sovaldi and Viekirax.
Danish: PRAC anbefaler følgeligt ændringen af betingelserne for markedsføringstilladelserne for Daklinza, Exviera, Harvoni, Olysio, Sovaldi og Viekirax.
English: In conclusion, the PRAC considered that the benefit-risk balance of DAAs-containing products remained favourable subject to the amendments of the terms of the marketing authorisations.
Danish: Afslutningsvist fandt PRAC, at benefit/risk-forholdet for DAA-holdige produkter stadig er positivt, såfremt de anbefalede ændringer blev implementeret i betingelserne i markedsføringstilladelserne.
English: In accordance with the PRAC recommendation, in order to evaluate the recurrence of hepatocellular carcinoma associated with direct-acting antivirals, the MAHs shall conduct and submit the results of a prospective safety study using data deriving from a cohort of a well-defined group of patients, based on an agreed protocol setting out criteria for entry and follow-up of patients in terms of timing and method for screening.
Danish: I overensstemmelse med anbefalingen fra PRAC skal indehaverne af markedsføringstilladelserne, for at kunne vurdere recidiv af hepatocellulært carcinom i forbindelse med direkte aktive antivirale lægemidler, gennemføre og indsende resultaterne af en prospektiv sikkerhedsundersøgelse ved brug af data fra en kohorte bestående af en veldefineret patientgruppe, baseret på en i fællesskab vedtaget protokol med kriterier for inkludering og opfølgning af patienter med hensyn til screeningstidspunkt og -metode.
English: All MAHs of DAAs shall conduct a prospective safety study in a well-defined group of patients based on an agreed protocol setting out criteria for entry and follow-up.
Danish: Alle indehavere af markedsføringstilladelser til DAA'er skal gennemføre en prospektiv sikkerhedsundersøgelse hos en veldefineret patientgruppe baseret på en i fællesskab vedtaget protokol med kriterier for inkludering og opfølgning.
English: Taking all available data into account, the PRAC was of the view that MAHs should conduct and submit the results of a prospective safety study using data deriving from a cohort of a well-defined group of patients, based on an agreed protocol setting out criteria for entry and follow-up of patients in terms of timing and method for screening.
Danish: Under hensyntagen til alle tilgængelige data fandt PRAC, at indehaverne af markedsføringstilladelserne skal gennemføre og indsende resultaterne af en prospektiv sikkerhedsundersøgelse ved brug af data fra en kohorte bestående af en veldefineret patientgruppe, baseret på en i fællesskab vedtaget protokol med kriterier for inklusion og opfølgning af patienter med hensyn til screeningstidspunkt og -metode.
English: A study from Reig et al. (2016) showed a signal of HCC recurrence in patients treated with DAAs; similar results were obtained by Conti et al. (2016).
Danish: En undersøgelse fra Reig et al. (2016) viste et signal for HCC-recidiv hos patienter behandlet med DAA'er.