natgillin/translations-raw huggingface dataset:
Bivirkninger (ADR) er anført i Tabel 1 efter systemisk organklasse.
Adverse Drug Reactions (ADRs) are listed in Table 1 by System Organ Class.
De anførte ADR er rapporteret hos mere end 1 patient og vises som en procentdel af patienter, der har oplevet den pågældende ADR, med det faktiske antal patienter i parentes.
The ADRs listed are reported in more than 1 patient and shown as percentage of patients experiencing the ADR with the absolute number of patients in brackets.
ADR var for det meste milde til moderate og forekom næsten alle under infusionen eller i de 2 timer umiddelbart efter infusionen (infusionsrelaterede reaktioner, IAR' er).
ADRs were mostly mild to moderate in intensity and almost all occurred during the infusion or during the 2 hours following the infusion (infusion associated reactions, IARs).
Alvorlige infusionsreaktioner, så som urticaria, rallen, takykardi, reduceret iltmætning, bronkospasme, tachypnea, periorbitalt ødem og hypertension er blevet rapporteret.
Serious infusion reactions including urticaria, rales, tachycardia, decreased oxygen saturation, bronchospasm, tachypnea, periorbital edema and hypertension have been reported.
4 Tabel 1.
4 Table 1.
Bivirkninger hos mere end 1 patient efter systemisk organklasse.
Adverse Drug Reactions by System Organ Class in more than one patient.
Systemisk organklasse
System Organ Class
Foretrukken betegnelse
Preferred term
Frekvens (antal patienter) N = 39
Frequency (no. of patients) N = 39
Psykiatriske sygdomme Sygdomme i nervesystemet Hjertesygdomme
Psychiatric disorders Nervous system disorders Cardiac disorders
Uro Tremor Takykardi
Agitation Tremor Tachycardia Cyanosis
5% (2 patienter) 5% (2 patienter) 10% (4 patienter)
5% (2 pts) 5% (2 pts) 10% (4 pts) 5% (2 pts)
Hypertension Bleghed
Flushing Hypertension Pallor
8% (3 patienter) 5% (2 patienter)
13% (5 pts) 8% (3 pts) 5% (2 pts)
Respiratoriske, torakale og mediastinale sygdomme
Respiratory, thoracic and mediastinal Cough disorders
13% (5 patienter) 13% (5 patienter)
13% (5 pts)
Gastrointestinale sygdomme
Tachypnoea Gastrointestinal disorders Vomiting Retching Nausea Skin and subcutaneous tissue Urticaria disorders
18% (7 patienter)
13% (5 pts) 10% (4 pts) 5% (2 pts) 5% (2 pts) 18% (7 pts)
Maculært udslæt Erytem Maculo- papulært udslæt Papulært udslæt Pruritis
Rash Rash macular Erythema Rash maculo-papular Rash papular Pruritis General disorders and administration Pyrexia site conditions
28% (11 patienter) 5% (2 patienter) 5% (2 patienter)
15% (6 pts) 5% (2 pts) 8% (3 pts) 8% (3 pts) 5% (2 pts) 5% (2 pts) 28% (11 pts)
Forhøjet blodtryk Forhøjet kropstemperatur Forhøjet hjertefrekvens
Irritability Chills Investigations Oxygen saturation decreased Blood pressure increased Body temperature increased Heart rate increased
5% (2 patienter) 5% (2 patienter) 5% (2 patienter)
5% (2 pts) 5% (2 pts) 18% (7 pts) 5% (2 pts) 5% (2 pts) 5% (2 pts)
5. 1) er behandlet med Myozyme.
A limited number of patients with late-onset Pompe disease (see section 5.1) have been treated with Myozyme.
De ADR, der er rapporteret hos 2 af 9 patienter med sent debuterende sygdom, som blev behandlet med Myozyme i indtil 1 år i 3 forskellige undersøgelser, omfattede øget hjertefrekvens, hypertension, hovedpine, perifer kulde, paræstesi, rødmen, smerter på infusionsstedet, reaktioner på infektionsstedet, øget blodtryk og svimmelhed.
ADRs reported in 2 of 9 late-onset patients treated with Myozyme for up to 1 year in 3 different studies included increased heart rate, hypertension, headache, peripheral coldness, paresthesia, flushing, infusion site pain, infusion site reaction, increased blood pressure and dizziness.
De 2 sent debuterende patienter oplevede ikke samme ADR.
The 2 late onset patients did not experience the same ADRs.
ADR var milde og blev vurderet som en infusionsrelateret reaktion.
The ADRs were mild in intensity and assessed as an IAR.
Infusionsrelaterede reaktioner hos patienter, der er behandlet med Myozyme i kliniske undersøgelser og ” Expanded Access Programs ”, som er indberettet for mere end 1 patient, omfattede udslæt, rødmen, urticaria, pyrexi, hoste, takykardi, reduceret iltmætning, opkastning, tachypnoea, uro, forhøjet blodtryk, cyanose, hypertension, irritabilitet, bleghed, pruritus, kløgning, kulderystelser, tremor, hypotension, øget hjertefrekvens, bronkospasmer, erytem, ansigtsødem, varm fornemmelse, hovedpine, hyperhidrose, øget tåredannelse, livedo reticularis, kvalme, periorbitalt ødem, rastløshed 5 og hvæsende vejrtrækning.
IARs in patients treated with Myozyme in clinical studies and expanded access programs and reported in more than 1 patient included rash, flushing, urticaria, pyrexia, cough, tachycardia, decreased oxygen saturation, vomiting, tachypnea, agitation, increased blood pressure, cyanosis, hypertension, irritability, pallor, pruritus, retching, chills, tremor, hypotension, heart rate increased, bronchospasm, erythema, face edema, feeling hot, headache, hyperhidrosis, lacrimation increased, livedo reticularis, nausea, periorbital edema, restlessness and wheezing.
Infusionsrelaterede reaktioner, der blev rapporteret som svære hos mere end 1 patient, omfattede pyrexi, reduceret iltmætning, takykardi, cyanose og hypotension.
Those IARs reported as severe in more than 1 patient included pyrexia, decreased oxygen saturation, tachycardia, cyanosis and hypotension.
Der er rapporteret et enkelt tilfælde af angioneurotisk ødem af høj sværhedsgrad.
A single event of angioneurotic edema of severe intensity has been reported.
Et lille antal patienter (< 1%) fra kliniske undersøgelser og fra efter markedsføring udviklede anafylaktisk chok og/ eller hjertestop under infusion med Myozyme, som krævede genoplivningstiltag.
A small number of patients (< 1%) in clinical trials and in the commercial setting developed anaphylactic shock and/ or cardiac arrest during Myozyme infusion that required life-support measures.
Patienterne udviste en række tegn og symptomer, primært respiratoriske, kardiovaskulære, ødematøse og/ eller kutane af natur (se pkt.
Patients presented with a constellation of signs and symptoms, primarily respiratory, cardiovascular, edematous and/ or cutaneous in nature (see Section 4.4).
4. 4).
Patients
Patienter med moderate til svære eller recidiverende infusionsrelaterede reaktioner er vurderet for Myozyme - specifikke IgE- antistoffer; nogle patienter testedes positive, herunder en patient, der oplevede en anafylaktisk reaktion.
5 with moderate to severe or recurrent IARs have been evaluated for Myozyme specific IgE antibodies; some patients tested positive including one patient who experienced an anaphylactic reaction.
I kliniske undersøgelser blev der brugt doser på op til 40 mg/ kg kropsvægt.
In clinical studies doses up to 40 mg/ kg body weight were used.
Farmakoterapeutisk gruppe: produkter til fordøjelseskanalen og stofskiftet – enzymer.
Alimentary tract and metabolism products – enzymes.
A16AB07 alglukosidase alfa.
A16AB07 alglucosidase alfa.
Alglukosidase alfa er en rekombinant form af human sur α- glukosidase og fremstilles ved hjælp af rekombinant DNA- teknologi ud fra kinesisk hamster ovarie( CHO) cellekultur.
Alglucosidase alfa is a recombinant form of human acid α -glucosidase and is produced by recombinant DNA technology using Chinese Hamster Ovary (CHO) cell culture.
Pompes sygdom Pompes sygdom er en sjælden, progressiv og dødelig stofskifte- myopati med en anslået global forekomst på 1 ud af 40. 000 fødsler.
Pompe disease Pompe disease is a rare, progressive and fatal metabolic myopathy with an estimated global incidence of 1 in 40,000 births.
Andre navne for Pompes sygdom er ” glycogen storage disease type II ” (GSD- II), ” sur maltase deficiency ” (AMD) og ” glykogonesis type II ”.
Other names for Pompe disease include glycogen storage disease type II (GSD- II), acid maltase deficiency (AMD) and glycogenosis type II.
Pompes sygdom tilhører de lysosomale aflejringssygdomme, idet den skyldes en mangel på en naturligt forekommende lysosomal hydrolase, sur α- glukosidase (GAA), der nedbryder lysosomal glykogen til glukose.
Pompe disease belongs to the lysosomal storage disorders as it is caused by a deficiency of a naturally-occurring lysosomal hydrolase, acid α - glucosidase (GAA) that degrades lysosomal glycogen to glucose.
Mangel på dette enzym medfører glykogen- ophobning i forskellige væv, især hjerte -, åndedræts - og skeletalmuskler, hvilket medfører udvikling af hypertrofisk kardiomyopati og progressiv muskelsvækkelse, herunder svækkelse af åndedrætsfunktionen.
Deficiency of this enzyme leads to glycogen accumulation in various tissues, particularly cardiac, respiratory and skeletal muscle, leading to the development of hypertrophic cardiomyopathy and progressive muscle weakness, including impairment of respiratory function.
Død indtræder typisk som følge af hjertestop og/ eller respirationssvigt inden 1 års alderen.
Death typically occurs due to cardiac and/ or respiratory failure before the age of one year.
I en retrospektiv observations undersøgelse af patienter med Pompes sygdom med debut i spædsbørnsalderen (n=168) var den mediane alder ved symptomernes debut 2, 0 måneder og den mediane alder ved død 9, 0 måneder.
In a retrospective natural history study in patients with infantile-onset Pompe disease (n=168), the median age at onset of symptoms was 2.0 months and the median age of death was 9.0 months.
Kaplan- Meier overlevelsesrater ved 12, 24 og 36 måneders alderen var henholdsvis 26%, 9% og 7%.
Kaplan-Meier survival rates at 12, 24 and 36 months of age were 26%, 9% and 7%, respectively.
6 Den sent debuterende form af Pompes sygdom manifesterer sig i løbet af spædbørnsalderen, barndommen, ungdommen eller endda voksenalderen og er langt mindre hastigt progredierende end formen med debut i spædbørnsalderen.
The late-onset form of Pompe disease manifests during infancy, childhood, adolescence or even adulthood and is much less rapidly progressive than the infantile-onset form.
Som regel kendetegnes den ved tilstedeværelsen af tilstrækkelig resterende GAA- aktivitet, hvilket forhindrer udviklingen af kardiomyopati, men nogen involvering af hjertet er rapporteret hos op til ca.
Usually, it is characterised by the presence of sufficient residual GAA activity to preclude the development of cardiomyopathy, however some cardiac involvement has been reported in up to approximately 4% of patients with late-onset Pompe disease.
4% af patienter med sent debuterende Pompes sygdom.
The time course of disease progression is extremely variable and not predictable, with some patients experiencing a rapid deterioration in skeletal and respiratory muscle function leading to loss of
Tidsforløbet for sygdommens udvikling varierer meget og er ikke forudsigelig, da nogle patienter oplever en hurtig forringelse i skeletal - og åndedrætsmuskelfunktion, som medfører tab af mobilitet og respirationssvigt, andre progredierer mindre hurtigt, og atter andre præsenterer sig med en adskillelse mellem progressionen af skeletal - og åndedrætsmuskel involvering.
6 ambulation and respiratory failure, others progressing less rapidly, and yet others presenting with a dissociation in the progression of skeletal and respiratory muscle involvement.
Det påstås, at Myozyme vil genoprette lysosomal GAA- aktivitet, hvilket medfører stabilisering eller genoprettelse af hjerte - og skeletalmuskelfunktion (herunder åndedrætsmuskler).
It is postulated that Myozyme will restore lysosomal GAA activity resulting in stabilisation or restoration of cardiac and skeletal muscle function (including respiratory muscles).
På grund af blod - hjernebarrierens virkning og enzymets størrelse er optagelse af alglukosidase alfa i centralnervesystemet usandsynlig.
Due to the blood- brain barrier effect and the enzyme’ s size, uptake of alglucosidase alfa in the central nervous system is unlikely.
Pompes sygdom med debut i spædbørnsalderen; klinisk forsøg med patientalder op til 6 måneder Sikkerhed og effekt for Myozyme er vurderet i en randomiseret, open- label, historisk kontrolleret klinisk pivotalundersøgelse med 18 ikke- ventilerede patienter med sygdomsdebut i spædbørnsalderen og i alderen 6 måneder eller mindre ved behandlingens start.
Infantile-onset Pompe disease; clinical trial in patients aged 6 months or less The safety and efficacy of Myozyme was assessed in a pivotal, randomised, open-label, historically- controlled clinical trial of 18 non-ventilated infantile-onset patients aged 6 months or less at the onset of treatment.
Den ubehandlede, historiske patientgruppe var i overensstemmelse med pivotalundersøgelsens population og var afledt fra en retrospektiv naturlig anamneseundersøgelse (n=42) hos patienter med Pompes sygdom med debut i spædbørnsalderen.
The untreated historical cohort was matched to the pivotal study population and was derived from a retrospective natural history study (n=42) in patients with infantile-onset Pompe disease.
Patienterne blev randomiseret til at få enten 20 mg/ kg eller 40 mg/ kg hver anden uge i en periode på 52 uger.
Patients were randomized to receive either 20 mg/ kg or 40 mg/ kg every two weeks for a period of 52 weeks.
Efter mindst 52 uger blev 16 af disse 18 patienter rekrutteret til en udvidet undersøgelse og fik fortsat behandling med samme dosis med en samlet varighed på op til tre år (150 uger).
After a minimum of 52 weeks, 16 of these 18 patients were enrolled in an extension study to receive continued treatment at the same dose for a total duration of up to three years (150 weeks).
Det primære endpoint var andelen af patienter, som var i live og fri for invasiv ventilator.
The primary endpoint was the proportion of patients who were alive and free of invasive ventilator support.
Overlevelsen fri for invasiv ventilator blev dog ikke registreret i den ubehandlede, historiske gruppe, og en sammenligning af dette endpoint er ikke mulig.
However, the invasive ventilator-free survival was not recorded in the untreated historical cohort and a comparison of this endpoint is not possible.
Efter 52 ugers behandling var alle 18 patienter, der blev behandlet med Myozome, i live og 15 ud af 18 patienter i live og fri for invasiv ventilatorstøtte, hvorimod 1 af 42 patienter i den ubehandlede, historiske gruppe var i live ved 18 måneders alderen.
After 52 weeks of treatment, all 18 patients treated with Myozyme were alive and 15 of these 18 patients were alive and free of invasive ventilatory support whereas 1 of 42 patients in the untreated historical cohort was alive at 18 months of age.
To patienter døde og deltog ikke i den forlængede undersøgelse.
Two patients died and did not enter into the extension study.
Efter 104 ugers behandling var alle 16 patienter, som blev rekrutteret til den forlængede undersøgelse, i live, og 10 ud af disse 16 patienter var fri for invasiv ventilation.
After 104 weeks of treatment, all 16 patients who enrolled in the extension study were alive and 10 of these 16 patients were free of invasive ventilatory support.
Ved afslutningen af undersøgelsen (med individuelle patientbehandlingsvarigheder fra 60 til 150 uger: gennemsnitlig opfølgningsperiode på 119 uger) var 14 af 16 patienter i live, og 9 af 16 patienter var i live og fri for invasiv ventilator.
At the end of the study (with individual patient treatment durations ranging from 60 to 150 weeks; mean follow-up period of 119 weeks) 14 of 16 patients were alive and 9 of 16 patients were alive and free of invasive ventilatory support.
Endnu en patient døde efter undersøgelsens afslutning og endnu en efter udtræden fra undersøgelsen.
One additional patient died after study end and another one after withdrawal from the study.
Patienter, der blev behandlet med Myozyme, udviste længerevarende overlevelse sammenlignet med overlevelsen i den ubehandlede historiske gruppe (se tabel 2).
Patients treated with Myozyme demonstrated prolonged survival as compared to survival in an untreated historical cohort (see Table 2).
7 Tabel 2:
7 Table 2:
Resultater for endpoint overlevelse ved hjælp af Cox- regressionsmodel
Results for endpoint survival using the Cox regression model
Historisk
Treatment
Ratio mellem 95%
95%
Behandlede reference -
Effect Hazard Confidence
behandlings -
Patients
konfidens -
Comparator
patienter komparator Endpoint
Endpoint
effekt og risiko
Ratio Interval
(0, 015, 0, 147)
(0.015, 0.147) < 0.0001
< 0, 0001
Note:
Resultaterne er fra en Cox proportionel risiko regressions analyse, der involverer behandling som en tidsvarierende kovariat samt alder ved diagnose og alder ved symptomdebut.
Results are from a Cox proportional hazards regression analysis which includes treatment as a time-varying covariate, and also includes age of diagnosis and age at symptom onset.
Efter 104 ugers behandling var LVM - vurderingerne tilgængelige for 8 patienter, hvoraf værdien faldt til indenfor normalgrænserne hos 5.
At 104 weeks of treatment LVM assessments were available for 8 patients, of which 5 decreased to within normal limits.
Målt efter motorisk præstation i form af aldersækvivalente scorer på Alberta Infant Motor Scale (AIMS) opnåede syv af 18 patienter bedre motorisk funktion under undersøgelsen og kunne gå selv ved den sidste vurdering (med individuelle patientbehandlingsvarigheder fra 52 til 130 uger: gennemsnitlig opfølgningsperiode på 94 uger).
As measured by motor performance age-equivalent scores of the Alberta Infant Motor Scale (AIMS), seven of the 18 patients made motor development gains during the study and were walking independently by the last study assessment (with individual patient treatment durations ranging from 52 to 130 weeks; mean follow-up period of 94 weeks).
Yderligere 4 patienter opnåede bedre motorisk funktion under undersøgelsen og kunne sidde selv ved den sidste vurdering (med individuelle patientbehandlingsvarigheder fra 78 til 130 uger: gennemsnitlig opfølgningsperiode på 110 uger), selvom de ikke kunne bruge benene.
An additional 4 patients made motor development gains during the study and were sitting independently by the last study assessment (with individual patient treatment durations ranging from 78 to 130 weeks; mean follow-up period of 110 weeks), although they did not have functional use of the legs.
Efter 52 ugers behandling havde 14 af 18 patienter (77, 8%) opnået vedligeholdelse eller forbedring i vægt/ alder- percentilen (over 3. percentil), 14 af 15 patienter (93, 3%) var over den 3. percentil for højde, og 12 af 15 patienter (80, 0%) var over den 3. percentil for hovedomkreds.
After 52 weeks of treatment 14 of 18 patients (77.8%) had maintained or improved weight-for-age percentiles (above the 3rd percentile), 14 of 15 patients (93.3%) were above the 3rd percentile for length and 12 of 15 patients (80.0%) were above the 3rd percentile for head circumference.
I det andet behandlingsår havde 15 af 17 patienter opnået en yderligere forbedring i vægt/ alder- percentilen (med individuelle patientbehandlingsvarigheder fra 78 til 142 uger: gennemsnitlig opfølgningsperiode på 111 uger), 10 af 16 patienter havde opnået en yderligere forbedring i længe/ alder- percentilen (med individuelle patientbehandlingsvarigheder fra 90 til 130 uger: gennemsnitlig opfølgningsperiode på 113 uger), og 11 af 15 patienter havde opnået en yderligere forbedring i hovedomkreds/ alder - percentilen (med individuelle patientbehandlingsvarigheder fra 90 til 130 uger: gennemsnitlig opfølgningsperiode på 110 uger).
In the second year of treatment, 15 out of 17 patients had further improved weight-for-age percentiles (with individual patient treatment durations ranging from 78 to 142 weeks; mean follow-up period of 111 weeks), 10 out of 16 patients had further improved length-for-age percentiles (with individual patient treatment durations ranging from 90 to 130 weeks; mean follow-up period of 113 weeks) and 11 out of 15 patients had further improved head circumference-for-age percentiles (with individual patient treatment durations ranging from 90 to 130 weeks; mean follow-up period of 110 weeks).
Efter 104 ugers behandling havde alle 13 patienter med tilgængelige data opnået vedligeholdelse eller forbedring af vægt/ alder- percentilen (over 3. percentil), alle 12 patienter med tilgængelige data var over den 3. percentil for højde, og alle 12 patienter med tilgængelige data var over den 3. percentil for hovedomkreds.
At 104 weeks of treatment, all 13 patients with available data had maintained or improved weight-for-age percentiles (above the 3rd percentile), all 12 patients with available data were above the 3rd percentile for length and all 12 patients with available data were above the 3rd percentile for head circumference.
Analyser af effekt afslørede ingen forskelle af betydning mellem de 2 dosisgrupper med hensyn til overlevelse, overlevelse fri for invasiv ventilator, overlevelse uden nogen form for ventilator, fald i LVM, forøgning i vækstparametre og opnåelse af motoriske milepæle.
Analyses of efficacy did not reveal meaningful differences between the 2 dose groups with respect to survival, invasive ventilator-free survival, any ventilator-free survival, decrease in LVM, gains in growth parameters and acquisition of motor milestones.
Baseret på disse resultater anbefales dosen 20 mg/ kg hver anden uge.
Based on these results the 20 mg/ kg qow dose is recommended.
Pompes sygdom med debut i spædbørnsalderen; klinisk forsøg med patientalder fra 6 måneder til 3, 5 år En anden open- label undersøgelse vurderede ligeledes sikkerhed og effekt af Myozyme hos 21 patienter med hovedsagelig den a- typiske form for Pompes sygdom med debut i spædbørnsalderen, der var fra 6 måneder til 3, 5 år ved behandlingens start.
Infantile-onset Pompe disease; clinical trial in patients aged 6 months to 3.5 years A second open-label clinical trial also assessed the safety and efficacy of Myozyme in 21 patients with predominantly a non-typical form of infantile-onset Pompe disease who ranged in age from 6 months to 3.5 years at initiation of treatment.
Patienterne fik 20 mg/ kg Myozyme hver anden uge i 52 uger med undtagelse af 8 patienter, der fik 40 mg/ kg efter mindst 26 ugers behandling.
Patients received 20 mg/ kg Myozyme every other week for 52 weeks except for 8 patients who received 40 mg/ kg after at least 26 weeks of treatment.
8 Efter 52 uger fortsatte alle patienter med behandling med en samlet varighed på op til mere end 3 år (168 uger med en median på 121 uger).
After 52 weeks all patients continued treatment for a total duration of more than 3 years (168 weeks with a median of 121 weeks).
Det primære endpoint for den pivotale undersøgelse var andelen af patienter, som var i live.
8 The primary endpoint of the pivotal trial was the proportion of patients who were alive.
Efter 52 ugers behandling var 16 af 21 patienter i live (76, 2%), som blev behandlet med Myozyme.
After 52 weeks of treatment, 16 of 21 patients (76.2%) treated with Myozyme were alive.
Efter 104 ugers behandling var 14 af 21 patienter i live (66, 7%), og 1 patient var i live, men var trådt ud af forsøget.
After 104 weeks of treatment, 14 of 21 patients (66.7%) were alive and 1 patient was alive but had discontinued from the study.
Disse andele blev opretholdt indtil afslutningen af undersøgelsen (med individuelle patientbehandlingsvarigheder mellem 1 og 168 uger: gennemsnitlig opfølgningsperiode på 109 uger).
These proportions were maintained up to the end of the study (with individual patient treatment durations ranging from 1 to 168 weeks; mean follow-up period of 109 weeks).
I den ubehandlede, historiske gruppe var 5 af 47 patienter (10, 6%) med tilgængelige data i live ved alderen 30 måneder (2, 5 år).
In the untreated historical cohort 5 of 47 patients (10.6%) for whom data were available, were alive at age 30 months (2.5 years).
Overlevelse hos de behandlede patienter blev sammenlignet med overlevelse hos en lignende historisk gruppe af ubehandlede forsøgspersoner ved hjælp af en Cox proportionel risiko regressions analyse (se Tabel 3).
Survival in the treated patients was compared to survival in a similar historical cohort of untreated subjects using a Cox proportional hazards regression analysis (See Table 3).