qanastek/EMEA-V3 huggingface dataset:
These reactions are listed in table 4 by system organ class and frequency (very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000) or not known.
Dawn ir - reazzjonijiet huma elenkati f’ tabella 4 skond il- klassi tas- sistema ta ’ l- organi u l- frekwenza (komuni ħafna (≥ 1/ 10), komuni (≥ 1/ 100 sa < 1/ 10), mhux komuni (≥ 1/ 1, 000 sa < 1/ 100), rari (≥ 1/ 10, 000 sa < 1/ 1, 000), ari ħafna (< 1/ 10, 000) jew mhux magħruf.
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness
F’ kull sezzjoni ta ’ frekwenza, l- effetti mhux mixtieqa huma mniżżla skond is- serjetà tagħhom, bl- aktar serji jitniżżlu l- ewwel.
Adverse reactions reported in clinical trials or through post-marketing surveillance in patients treated with interferon alfa-2b, including PegIntron monotherapy or PegIntron + ribavirin.
Reazzjonijiet avversi irrappurtati fil- provi kliniċi jew minn sorveljenza f’ pazjenti kkurati b’ interferon alfa- 2b, inkluża monoteraija b’ PegIntron jew PegIntron ma ’ ribavirin.
Infection s and infestations Very common:
Infezzjonijiet u infestazzjonijiet Komuni ħafna:
Infection viral*
Infezzjoni virali *
Fungal infection, bacterial infection including sepsis, herpes simplex, otitis media
Infezzjonijiet tal- fungu, infezzjoni b’ batteri, inkluża sepsi, herpes simplex, otitis media
Anaemia, leukopaenia, thrombocytopaenia, lymphadenopathy
Anemija, lewkopenja, tromboċitopenja, limfadenopatija
Aplastic anaemia
Anemija alpastika
Frequency not known:
Frekwenza mhux magħrufa:
Pure red cell aplasia
Aplażja taċ- ċelluli ħomor pura
Sarcoidosis or exacerbation of sarcoidosis
Sarkojdożi jew sarkojdożi tiħrax
Acute hypersensitivity reactions including angioedema, anaphylaxis and anaphylactic reactions including anaphylactic shock, idiopathic thrombocytopenic purpura, thrombotic thrombocytopenic purpura, systemic lupus erythematosus, vasculitis, arthritis rheumatoid and arthritis rheumatoid aggravated
Reazzjonijiet ta ’ sensittività eċċessiva inkluża anġjoedema, anafilassi u reazzjonijiet anafilattiċi inklużi xokk anafilattiku, purpura tromboċitopenika idjopatika, purpura tromboċitopenika trombotika, lupus eritematosus sistemika, vaskulite, artrite rewmatika u artrite rewmatika aggravata.
11 Metabolism and nutrition disorders Very common:
Dijabete Disturbi fil- metaboliżmu u n - nutrizzjoni Komuni ħafna:
Weight decrease
Telf tal- piż
Hypocalcemia, hyperuricemia, thirst
Ipokalċimja, iperuriċimja, għatx
Depression, irritability, insomnia, anxiety*, concentration impaired, emotional lability*
Dipressjoni, irritabilità, nuqqas ta ’ rqad, ansjetà *, telf tal - konċentrazzjoni, burdati emozzjonali *
Aggressive behaviour, behaviour disorder, agitation, nervousness, somnolence, sleep disorder, dreaming abnormal, decreased libido, apathy, appetite increased
Imġieba aggressiva, disturbi fl- imġieba, aġitazzjoni, nervi, ngħas, disturbi fl- irqad, ħolm anormali, nuqqas fil- libido, apatija, nuqqas fl- aptit
Attempted suicide, suicidal ideation
Attentat ta ’ suwiċidju, ħsibijiet dwar suwiċidju
Psychosis, hallucination
Psikożi, alluċinazzjoni
Nervous system disorders
Disturbi fis- sistema nervuża Komuni ħafna:
Mania, bipolar disorders
Manija, disturbi bipolari Uġigħ ta ’ ras, ħalq xott *
Confusion, tremor, ataxia, neuralgia, vertigo, paresthesia, hypoaesthesia, hyperaesthesia, hypertonia, migraine, increased sweating
Konfużjoni, tregħid, atassja, newralġja, vertigo, parasteżija, iposteżija, iperesteżija, ipertonija, emigranja, żieda fl- għaraq
Seizure, peripheral neuropathy
Attakk tal- qamar, newropatija periferali Rari:
Very rare:
Emorraġija ċerebrovaskulari, iskemija ċerebrovaskulari, Rari ħafna:
Cerebrovascular haemorrhage, cerebrovascular ischaemia, encephalopathy
enċefelopatija
Facial palsy, neuropathies, mononeuropathies
Palsi tal- wiċċ, newropatiji, mononewropatiji
Conjunctivitis, blurred vision, lacrimal gland disorder, eye pain
Konġuntivite, vista mċajpra, disturbi fil- glandola tad- dmugħ, uġigħ fl- għajnejn.
Hearing impairment/loss, tinnitus
Nuqqas/ telf tas- smigħ, tisfir fil- widnejn
Palpitation, tachycardia
Palpitazzjoni, takikardija
Myocardial infarction, cardiac ischaemia
Infart mijokardijaku, iskemija kardijaka
Cardiomyopathy, pericardial effusion, pericarditis
Kardjomijopatija, effużjoni perikardijaka, perikardite
Respiratory, thoracic and mediastinal disorders
Disturbi respiratorji, toraċiċi u medjastinali Komuni ħafna:
Hypotension, hypertension, syncope, flushing
Pressjoni baxxa, pressjoni għolja, sinkope, fwawar Qtugħ ta ’ nifs *, farinġite *, sogħla *
Interstitial lung disease 12
Disturbi gastro- intestinali Komuni ħafna:
Vomiting*, nausea, abdominal pain, diarrhoea, anorexia
Sinusite, bronkite, disfonja, epistassi, infjammazzjoni tal - passaġġi mukużi ta ’ l- imnieħer, disturbi respiratorji, konġestjoni ta ’ l- imnieħer, flissjoni, sogħla fil- vojt Mard fl- interstizzju tal- pulmun Rimettar *, dardir, uġigħ fl- addome, dijarea, anoressija
Dyspepsia, gastroesophageal reflux, stomatitis, ulcerative stomatitis, gingival bleeding, loose stools, constipation, flatulence, hemorrhoids, gingivitis, glossitis, dehydration, taste perversion
Dispepsja, ittella ’ mill- istonku, stomatite, stomatite b’ ulċera, fsada tal- ħanek, ippurgar maħlul, stitikezza, gass fl- istonku, emorrojdi, ġenġivite, glossite, deidratazzjoni, perverżjoni tat - togħma
Pancreatitis
Infezzjoni fil- frixa
Ischaemic colitis, ulcerative colitis
Kolite iskemika, kolite b’ ulċera
Skin and subcutaneous tissue disorders
Disturbi fil- ġilda u fit- tessuti ta ’ taħt il- ġilda Komuni ħafna:
Alopecia, pruritus*, skin dry*, rash*
Epatomegalija, iperbilirubinimja Alopeċja, ħakk *, ġilda xotta *, raxx *
Psoriasis, photosensitivity reaction, maculopapular rash, dermatitis, face or peripheral oedema, erythematous rash, eczema, acne, furunculosis, erythema, urticaria, abnormal hair texture, nail disorder
Psorajiżi, reazzjoni ta ’ fotosensittività, raxx makulopapulari, dermatite, edema tal- wiċċ jew periferali, raxx bi ħmura, ekżema, akne, furunkolite, ħmura, urtikarja, għamla tax- xagħar mhux normali, disturbi fid- dwiefer,
Stevens Johnson syndrome, toxic epidermal necrolysis, injection site necrosis, erythema multiforme
Sindrome ta ’ Stevens Johnson, nekroloiżi tossika ta ’ l- epidermide, nekrożi fis- sit mnejn tingħata l- injezzjoni, erythema multiforme
Myalgia, arthralgia, musculoskeletal pain
Mijalġja, artralġja, uġigħ muskoluskeletrali
Rhabdomyolysis, myositis Renal and urinary disorders Common:
Rabdomajelożi, mijosite Disturbi fil- kliewi u fis - sistema urinarja Komuni:
Micturition frequency, urine abnormal
Frekwenza ta ’ l- awrina, awrina anormali
Renal failure, renal insufficiency
Indeboliment renali, insuffiċjenza renali
Amenorrhoea, impotence, breast pain, menorrhagia, menstrual disorder, ovarian disorder, vaginal disorder, sexual dysfunction (not specified), prostatitis
Ma jkunx hemm mestrwazzjoni, impotenza, uġigħ tas- sider, uġigħ tal- mestrwazzjoni, disturbi mestrwali, disturbi fl- ovarji, disturbi fil- vaġina, funzjoni sesswali ħażina (mhux speċifikat), infjammazzjoni fil- prostata
Injection site inflammation, injection site reaction*, dizziness, fatigue, rigors, fever, flu-like symptoms, asthenia
Infjammazzjoni fis- sit mnejn tingħata l- injezzjoni, reazzjoni fis - sit mnejn tingħata l- injezzjoni *, sturdament, għeja, tregħid, deni, sintomi bħal ta ’ l- influwenza, astenja
Common: *
Komuni: *
Chest pain, RUQ pain, malaise, injection site pain
Uġigħ fis- sider, Uġigħ RUQ, tħossok ma tiflaħx, uġigħ fis- sit mnejn tingħata l- injezzjoni
These adverse reactions were common (≥1/100 to < 1/10) in clinical trials in patients treated with PegIntron monotherapy.
Dawn ir- reazzjonijiet avversi kienu komuni (≥1/ 100 sa < 1/ 10) fi provi kliniċi f’ pazjenti kkurati b’ monoterapija b’ PegIntron.
Most cases of neutropaenia and thrombocytopaenia were mild (WHO grades 1 or 2).
Il- biċċa l- kbira tal- każijiet ta ’ newtropenja u tromboċitopenija kienu ħfief (Gradi ta ’ WHO 1 jew 2).
There were some cases of more severe neutropenia in patients treated with the recommended doses of PegIntron in combination with ribavirin (WHO grade 3:
Kien hemm xi każijiet ta ’ newtropenja iktar qawwija f’ pazjenti li ġew trattati bid- dożi rakkomandati ta ’ PegIntron flimkien ma 'ribavirin (Gradi ta ’ WHO 3:
39 of 186 [21%]; and WHO grade 4:
39 minn186 [21%]; u gradi ta ’ WHO 4:
13 of 186 [7%]).
13 minn 186 [7%]).
In a clinical trial, approximately 1.2% of patients treated with PegIntron or interferon alfa-2b in combination with ribavirin reported life-threatening psychiatric events during treatment.
Fi prova klinika, madwar 1. 2% tal- pazjenti li kienu trattati b’ PegIntron jew interferon alfa- 2b flimkien ma 'ribavirin rrapurtaw każijiet psikjatriċi waqt it- trattament.
These events included suicidal ideation and attempted suicide (see section 4.4).
Dawn l- każijiet kienu jinkludu ħsibijet dwar suwiċidju u attentati ta ’ suwiċidju (ara sezzjoni 4. 4).
13 Cardiovascular (CVS) adverse events, particularly arrhythmia, appeared to be correlated mostly with pre-existing CVS disease and prior therapy with cardiotoxic agents (see section 4.4).
Każijiet avversi kardjovaskulari (CVS), l- aktar arritmija, dehru li kellhom x’ jaqsmu l- aktar ma ’ mard pri - eżistenti CVS u ma ’ l- għotja ta ’ aġenti kardjotossiċi xi darba qabel (ara sezzjoni 4. 4).
Cardiomyopathy, that may be reversible upon discontinuation of interferon alpha, has been reported rarely in patients without prior evidence of cardiac disease.
Kardjomijopatija, li tista ’ tkun riversibbli wara t- twaqqif ta ’ interferon alpha, kienet rrappurtata rari f’ xi pazjenti li qatt ma kellhom qabel sintomi ta ’ mard kardijaku.
Ophthalmological disorders that have been reported rarely with alpha interferons include retinopathies (including macular oedema), retinal haemorrhages, retinal artery or vein obstruction, cotton wool spots, loss of visual acuity or visual field, optic neuritis, and papilloedema (see section 4.4).
Problemi tal- għajnejn illi ġew rrapuratati b' mod rari b’ alfa interferon jinkludu retinopatija (inkluż nefħa ta ’ l- ilma fil- makula), emorraġija fir- retina, imblokk fl- arterja jew vina tar- retina, tara t- tikek, nuqqas fil - vista jew fil- kamp viżiv, infjammazzjoni tan- nerv ottiku, u papillo- edema (ara sezzjoni 4. 4).
A wide variety of autoimmune and immune-mediated disorders have been reported with alpha interferons including thyroid disorders, systemic lupus erythematosus, rheumatoid arthritis (new or aggravated), idiopathic and thrombotic thrombocytopenic purpura, vasculitis, neuropathies including mononeuropathies and Vogt-Koyanagi-Harada syndrome (see also section 4.4, Autoimmune disorders).
Varjetà wiesa ’ ta ’ problemi awto- immuni jew li jseħħu permezz tas- sistema immunitarja ġew irrapportati b’ alpha interferon, inkluż mard tat- tirojde, eritematożi sistemika tat- tip lupus, artrite rewmatika (tibda jew tiħrax), tromboċitopenja idjopatika u pupurika trombotika, infjammazzjoni vaskulari, u newropatiji li jinkludu mononewropatiji u sindrome Vogt- Koyanagi- Harada (ara wkoll sezzjoni 4. 4 Disturbi awto- immuni).
HCV/HIV co-infected patients For HCV/HIV co-infected patients receiving PegIntron in combination with ribavirin, other undesirable effects (that were not reported in mono-infected patients) which have been reported in the larger studies with a frequency > 5% were: oral candidiasis (14%), lipodystrophy acquired (13%), CD4 lymphocytes decreased (8%), appetite decreased (8%), gamma-glutamyltransferase increased (9%), back pain (5%), blood amylase increased (6%), blood lactic acid increased (5%), cytolytic hepatitis (6%), lipase increased (6%) and pain in limb (6%).
Pazjenti infettati fl- istess ħin b’ HCV/ HIV Għall- pazjenti infettati fl- istess ħin b’ HCV/ HIV li qed jirċievu PegIntron f’ kombinazzjoni ma ’ ribavirin, effetti oħra mhux mixtieqa (li ma kienux irrappurtati f’ pazjenti b’ infezzjoni waħda) li kienu irrappurtati fl - istudji b’ frekwenza ta ’ > 5% kienu: kandidijażi orali (14%), lipodistrofija akkwiżita (13%), tnaqqis fil - limfoċiti CD4 (8%), tnaqqis fl- aptit (8%), żieda tal- gamma- glutamyltransferase (9%), uġigħ fid- dahar (5%), żieda ta ’ l- amylase fid- demm (6%), żieda tal- lactic acid fid- demm (5%), epatite ċitolitika (6%), żieda tal - lipase (6%) u uġigħ fir- riġel (6%).
Mitochondrial toxicity:
Tossiċità mitokondijali:
Mitochondrial toxicity and lactic acidosis have been reported in HIV-positive patients receiving NRTI regimen and associated ribavirin for co-HCV infection (see section 4.4).
Tossiċità mitokondrijali u aċidożi lattika kienu rrappurtati f’ pazjenti pożittivi għall- HIV li kienu qed jirċievu kors ta ’ NRTI u ribavirin assoċjat għall- infezzjoni fl- istess ħin b’ HCV (ara sezzjoni 4. 4).
Although haematological toxicities of neutropenia, thrombocytopenia and anaemia occurred more frequently in HCV/HIV co-infected patients, the majority could be managed by dose modification and rarely required premature discontinuation of treatment (see section 4.4).
Valuri tal- laboratorju għall- pazjenti infettati fl- istess ħim b’ HCV/ HIV Għalkemm tossiċitajiet ħematoloġiċi ta ’ newtropenija, tromboċitopenja u anemija seħħew b’ mod aktar frekwenti f’ pazjenti li kellhom fl- istess ħin infezzjoni b’ HCV/ HIV, il- parti l- kbira setgħu ikunu maniġġjati b’ tibdil fid- doża u rari kellhom bżonn iwaqqfu l- kura aktar kmieni (ara sezzjoni 4. 4).
Haematological abnormalities were more frequently reported in patients receiving Peg Intron in combination with ribavirin when compared to patients receiving interferon alfa-2b in combination with ribavirin.
Anormalitajiet ħematoloġiċi kienu rrappurtati b’ mod aktar frekwenti f’ pazjenti li kienu qed jirċievu PegIntron f’ kombinazzjoni ma ’ ribavirin meta mqabbel ma ’ pazjenti li kienu qed jirċievu interferon alfa- 2b flimkien ma ’ ribavirin.
In Study 1 (see section 5.1), decrease in absolute neutrophil count levels below 500 cells/mm3 was observed in 4% (8/194) of patients and decrease in platelets below 50,000/mm3 was observed in 4% (8/194) of patients receiving PegIntron in combination with ribavirin.
Fi Studju wieħed (ara sezzjoni 5. 1), tnaqqis fl- għadd assolut tan- newtrofili taħt il- 500 ċellula/ mm3 dehru f’ 4% (8/ 194) tal- pazjenti u tnaqqis fl- għadd tal- plejtlits għal taħt 50, 000/ mm3 deher f’ 4% (8/ 194) tal- pazjenti li kienu qed jirċievu PegIntron f’ kombinazzjoni ma ’ ma ’ ribavirin.
Anaemia (hemoglobin < 9.4g/dl) was reported in 12% (23/194) of patients treated with PegIntron in combination with ribavirin.
Anemija (ħemoglobina < 9. 4g/ dl) kienet irrappurtata f’ 12% (23/ 194) tal- pazjenti ikkurati b’ PegIntron f’ kombinazzjoni ma ’ ribavirin.
CD4 lymphocytes decrease:
Tnaqqis fil- limfoċiti CD4:
Treatment with PegIntron in combination with ribavirin was associated with decreases in absolute CD4+ cell counts within the first 4 weeks without a reduction in CD4+ cell percentage.
Kura b’ PegIntron f’ kombinazzjoni ma ’ ribavirin kienet assoċjata ma ’ tnaqqis fl- għadd assolut ta ’ ċelluli CD4+ fl- ewwel 4 ġimgħat mingħajr tnaqqis fil- perċentwali taċ- ċelluli CD4+.
The decrease in CD4+ cell counts was reversible upon dose reduction or cessation of therapy.
It- tnaqqis fl- għadd ta ’ ċelluli CD4+ kien riversibbli bi tnaqqis tad- doża jew twaqqif tat- terapija.
The use of PegIntron in combination with ribavirin had no observable negative impact on the control of HIV viraemia during therapy or follow-up.
L- użu ta ’ PegIntron f’ kombinazzjoni ma ’ ribavirin ma deherx li kellu impatt negattiv fuq il- kontroll ta ’ virimja bl- HIV waqt it- terapija jew fiż - żmien ta ’ follow- up.
Limited safety data (N= 25) are available in co-infected patients with CD4+ cell counts < 200/µl (see section 4.4).
Hemm tgħarif limitat dwar is- sigurtà (N=25) f’ pazjenti li jkollhom infezzjoni fl- istess ħin b’ għadd ta ’ ċelluli CD4+ < 200µl (ara sezzjoni 4. 4).
Please refer to the respective Summary of Product Characteristics of the antiretroviral medicinal products that are to be taken concurrently with HCV therapy for awareness and management of toxicities specific for each product and the potential for overlapping toxicities with PegIntron in combination with ribavirin.
Jekk jogħġbok irreferi għas- Sommarju tal- Karatteristiċi tal- Prodott tal- prodotti mediċinali antiretrovirali li jkollhom jittieħdu fl- istes ħin ma ’ terapija HCV għall- għarfien u maniġġjar tat- tossiċitajiet speċifiċi għal kull prodott u l- potenzjal li jista ’ jkun hemm tossiċitajiet f’ daqqa b’ PegIntron f’ kombinazzjoni ma ’ ribavirin.
Doses up to 10.5 times the intended dose have been reported.
Dożi sa 10. 5- il darba d- doża intiża kienu rrappurtati.
The maximum daily dose reported is 1,200 µg for one day.
L- ogħla doża rrappurtata kuljum hija ta ’ 1, 200 μg f’ ġurnata waħda.
In general, the adverse events seen in overdose cases involving PegIntron are consistent with the known safety profile for PegIntron; however, the severity of the events may be increased.
B’ mod ġenerali, il- każijiet avversi li dehru f’ każijiet ta ’ doża eċċessiva li kienu jinvolvu PegIntron huma konsistenti mal- profil ta ’ sigurtà maghruf għal PegIntron; madankollu, is- severità tal - każijiet tista ’ tiżdied.
Standard methods to increase elimination of the medicinal product, e.g., dialysis, have not been shown to be useful.
Metodi standard biex tiżdied l- eliminazzjoni tal- prodott mediċinali, eż dijalisi, ma ntwerewx li kienu utli.
No specific antidote for PegIntron is available; therefore, symptomatic treatment and close observation of the patient are recommended in cases of overdose.
M’ hemm l- ebda antidotu speċifiku għal PegIntron; għalhekk, kura sintomatika o osservaz+zjoni mill- qrib tal- pazjent hija rakkomandata f’ każijiet ta ’ doża eċċessiva.
If available, prescribers are advised to consult with a poison control centre (PCC).
Jekk ikun hemm, it - tobba li jordnawh huma konsiljati li jirreferu għal ċentru tal- kontroll tal- veleni (PCC).
Immunostimulants, Cytokines and immunomodulators, Interferons, Peginterferon alfa-2b, ATC code:
Immunostimulanti, Ċitokajns u immunomodulaturi, Interferoni, Peginterferon alfa- 2b, Kodiċi ATC:
Recombinant interferon alfa-2b is covalently conjugated with monomethoxy polyethylene glycol at an average degree of substitution of 1 mole of polymer/mole of protein.
Interferon alfa- 2b rikombinat huwa konjugat b’ mod kovalenti ma ’ monomethoxy polyethylene glycol bi grad medju ta ’ sostituzzjoni ta ’ mole 1 ta ’ polimer/ mole ta ’ proteina.
The average molecular mass is approximately 31,300 daltons of which the protein moiety constitutes approximately 19,300.
Il- massa molekulari medja hija madwar 31, 300 daltons li 19, 300 minnhom huma kostitwit minn proteina.
Interferon alfa-2b In vitro and in vivo studies suggest that the biological activity of PegIntron is derived from its interferon alfa-2b moiety.
Interferon alfa- 2b Studji in vitro u in vivo jissuġġerixxu li l- attività bijoloġika ta ’ PegIntron titnissel minn kull wieħed minn żewġ partijiet ta ’ interferon alfa- 2b.
Interferons exert their cellular activities by binding to specific membrane receptors on the cell surface.
Interferoni jeżerċitaw l- attività ċellulari tagħhom billi jintrabtu ma ’ riċetturi speċifiċi fir- rita fuq il- wiċċ taċ- ċellola.
Studies with other interferons have demonstrated species specificity.
Studji b’ interferoni oħra wrew speċifiċità għal kull speċi.
However, certain monkey species, e.g., Rhesus monkeys, are susceptible to pharmacodynamic stimulation upon exposure to human type 1 interferons.
Madankollu, ċertu speċi ta ’ xadini, eż, xadini ta ’ l- ispeċi Rhesus, huma suxxettibbli għal stimulazzjoni farmakodinamika meta dawn ikunu esposti għal interferon tat- tip- 1 tal- bniedem.
Once bound to the cell membrane, interferon initiates a complex sequence of intracellular events that include the induction of certain enzymes.
Ladarba jingħaqad mar- rita taċ- ċellula, interferon iqajjem sekwenza kumplessa ta ’ sitwazzjonijiet ġewwa ċ- cellula li jinkludu l- attivazzjoni ta ’ ċertu enżimi.
It is thought that this process, at least in part, is responsible for the various cellular responses to interferon, including inhibition of virus replication in virus- infected cells, suppression of cell proliferation and such immunomodulating activities as enhancement of the phagocytic activity of macrophages and augmentation of the specific cytotoxicity of lymphocytes for target cells.
Huwa maħsub illi dan il- proċess, għall- inqas parzjalment, huwa responsabbli għar- risponsi varji fiċ- cellula għal interferon, inkluż l- impediment tar - replikazzjoni ta ’ vajrusijiet f’ ċelluli infettati bil- vajrus, trażżin tal- proliferazzjoni ta ’ ċelluli u attivitajiet immunomodulaturi bħal ma huma tħarriex ta ’ l- attività fagoċitika ta ’ makrofaġi u żjieda fit- tossiċità ċellulari speċifika ta ’ limfoċiti fiċ- ċelluli immirati.
Any or all of these activities may contribute to interferon’s therapeutic effects.
Kull waħda minn dawn l- attivitajiet jew kollha kemm huma jistgħu jikkontribwixxu għall- effett terapewtiku ta ’ interferon.
Recombinant interferon alfa-2b also inhibits viral replication in vitro and in vivo.
L- interferon alfa- 2b rikombinanti jimpedixxi wkoll replikar tal- vajrus in vitro u in vivo.
Although the exact antiviral mode of action of recombinant interferon alfa-2b is unknown, it appears to alter the host cell metabolism.
Għalkemm il- mod eżatt kif jaħdem interferon alfa- 2b rikombinanti kontra l- vajrus mhux magħruf, jidher illi jbiddel il - metaboliżmu taċ- ċellula li tilqa ’ fiha.
This action inhibits viral replication or if replication occurs, the progeny virions are unable to leave the cell.
Dan jimpedixxi r- replikar tal- vajrus jew jekk ir- replikar iseħħ, il - vajrusijiet imnissla ma jkunux jistgħu jitilqu miċ- ċellula.
PegIntron PegIntron pharmacodynamics were assessed in a rising single-dose trial in healthy subjects by examining changes in oral temperature, concentrations of effector proteins such as serum neopterin and 2’5’- oligoadenylate synthetase (2’5’-OAS), as well as white cell and neutrophil counts.
PegIntron Il- farmakodinamiċi ta ’ PegIntron kienu mistħarrġa fi prova ta ’ doża waħda li tiżdied f’ suġġetti b’ saħħithom billi ġew mkejla bidliet fit- temperatura orali, konċentrazzjonijiet ta ’ proteini effetturi bħalma huma neopterin tas- serum u 2’ 5 ’ - oligoadenylate synthetase (2’ 5 ’ - OAS), kif ukoll in- numru ta ’ ċelluli bojod u tan- newtrofili.
Subjects treated with PegIntron showed mild dose-related elevations in body temperature.
Dawk illi kienu trattati b’ PegIntron urew zjieda żgħ ira fit- temperatura tal- ġisem li kienet konnessa mad- doża.
Following single doses of PegIntron between 0.25 and 2.0 micrograms/kg/week, serum neopterin concentration was increased in a dose- related manner.
Wara dożi singoli ta ’ PegIntron ta ’ bejn 0. 25 u 2. 0 mikrogrammi/ kg/ ġimgħa, il- konċentrazzjoni ta ’ neopterin fis- serum żdiedet b’ mod li kien relatat mad- doża.
Neutrophil and white cell count reductions at the end of week 4 correlated with the dose of PegIntron.
Tnaqqis fl- għadd ta ’ newtrofili u ċelloli bojod fl- aħħar tar- raba ġimgħa kien korrelatat mad- doża ta ’ PegIntron.
PegIntron clinical trials – Naïve patients Two pivotal trials have been conducted, one (C/I97-010) with PegIntron monotherapy; the other (C/I98-580) with PegIntron in combination with ribavirin.
Studji Kliniċi fuq PegIntron - Pazjenti li qatt ma kienu ħadu din il- kura qabel Saru żewġ studji pivitali, wieħed (C/ I97- 010) b’ monoterapija b’ Pegintron u l- ieħor (C/ I98- 580) b’ PegIntron flimkien ma 'ribavirin.
Eligible patients for these trials had chronic hepatitis C confirmed by a positive HCV-RNA polymerase chain reaction (PCR) assay (> 30 IU/ml), a liver biopsy consistent with a histological diagnosis of chronic hepatitis with no other cause for the chronic hepatitis, and abnormal serum ALT.
Pazjenti eliġibbli għal dawn l- istudji kellhom epatite Ċ kronika li kienet ikkonfermata b' assay pożittiv tar- reazzjonijiet katina bil- polymerase (PCR) ta ’ l- HCV- RNA (> 30 IU/ ml), bijopsija tal- fwied li taqbel mad- dijanjożi istoloġika ta ’ epatite kronika mingħajr kawżi oħra għall- epatite kronika, u ALT anormali fis- serum.
In the PegIntron monotherapy trial, a total of 916 naïve chronic hepatitis C patients were treated with PegIntron (0.5, 1.0 or 1.5 micrograms/kg/week) for one year with a follow-up period of six months.
Fl- istudju fejn intużat monoterapija b’ PegIntron, b’ kollox 916 pazjenti naïve b’ epatite Ċ kronika ġew ittrattati b 'PegIntron (0. 5, 1. 0 jew 1. 5 mikrogrammi/ kg/ ġimgħa) għal sena u mbagħad ġew osservati għal sitt xhur.
In addition, 303 patients received interferon alfa-2b (3 million International Units [MIU] three times a week) as a comparator.
Barra minn hekk, 303 pazjenti irċevew interferon alfa- 2b (3 miljun unità internazzjonali [MIU] tliet darbiet fil- ġimgħa) biex isir tqabbil.
This study showed that Peg Intron was superior to interferon alfa-2b (Table 5).
Dan l- istudju wera li PegIntron kien superjuri għal interferon alfa- 2b (Tabella 5).
15 following combination regimens: • Peg Intron (1.5 micrograms/kg/week) + ribavirin (800 mg/day), (n = 511). • PegIntron (1.5 micrograms/kg/week for one month followed by 0.5 microgram/kg/week for 11 months) + ribavirin (1,000/1,200 mg/day), (n = 514). • Interferon alfa-2b (3 MIU three times a week) + ribavirin (1,000/1,200 mg/day) (n = 505).
Fi prova fejn PegIntron intuża f’ kombinazzjoni, 1, 530 pazjent naïve ingħataw trattament għal sena b’ wieħed mill- korsijiet ikkumbinati li ġejjin: • PegIntron (1. 5 mikrogrammi/ kg/ ġimgħa) + ribavirin (800 mg kuljum), (n = 511). • PegIntron (1. 5 mikrogrammi/ kg/ ġimgħa għal xahar segwit 0. 5 mikrogrammi/ kg/ ġimgħa għal ħdax - il xahar) + ribavirin (1, 000/ 1, 200 mg kuljum), (n = 514). • Interferon alfa- 2b (3 MIU tlett darbiet fil- ġimgħa) + ribavirin (1, 000/ 1, 200 mg kuljum) (n = 505).
In this trial, the combination of PegIntron (1.5 micrograms/kg/week) and ribavirin was significantly more effective than the combination of interferon alfa-2b and ribavirin (Table 5), particularly in patients infected with Genotype 1 (Table 6).
F’ din il- prova, il- kombinazzjoni ta ’ PegIntron (1. 5 mikrogrammi/ kg/ ġimgħa) u ribavirin kien, b’ mod sinifikattiv, aktar effettiv mill- kombinazjoni ta ’ interferon alfa- 2b u ribavirin (Tabella 5), l- aktar f’ pazjenti infettati b’ Ġenotip 1 (Tabella 6).
Sustained response was assessed by the response rate six months after the cessation of treatment.
Reazzjoni sostnuta kienet evalwata bir- rata ta ’ reazzjoni sitt xhur wara li twaqqaf it- trattament.
HCV genotype and baseline virus load are prognostic factors which are known to affect response rates.
Il- ġenotip ta ’ HCV u l- linja bażi tal- virus load huma fatturi pronostiċi li huma magħrufin li jaffettwaw ir - rati ta ’ reazzjoni.
However, response rates in this trial were shown to be dependent also on the dose of ribavirin administered in combination with Peg Intron or interferon alfa-2b.
Madankollu intwera li r- rati ta ’ reazzjoni f’ dan l- istudju kienu jiddependu wkoll fuq id - doża ta ’ ribavirin li ngħatat flimkien ma 'PegIntron jew interferon alfa- 2b.
In those patients that received > 10.6 mg/kg ribavirin (800 mg dose in typical 75 kg patient), regardless of genotype or viral load, response rates were significantly higher than in those patients that received ≤ 10.6 mg/kg ribavirin (Table 6), while response rates in patients that received > 13.2 mg/kg ribavirin were even higher.
F’ dawk il- pazjenti li ngħataw iktar minn 10. 6 mg/ kg ribavirin (doża ta ’ 800 mg f’ pazjent tipiku li jiżen 75 kg), minkejja l- ġenotip jew il - viral load, ir- rati ta ’ reazzjoni kienu, b’ mod sinifikattiv, ogħla minn dawk tal- pazjenti li ngħataw inqas minn 10. 6 mg/ kg ribavirin (Tabella 6), filwaqt illi r- rati tar- reazzjoni f’ pazjenti li ngħataw > 13. 2 mg/ kg ribavirin kienu saħansitra ogħla.
Sustained virological response (% patients HCV negative) PegIntron monotherapy
Reazzjoni viroloġika
PegIntron + ribavirin
sostenuta (% ta ’ pazjenti negattivi għal HCV) Monoterapija b 'PegIntron PegIntron + ribavirin
Number of patients
Kors ta ’ trattament Numru ta ’ pazjenti
304
P 1. 5 304
297
P 1. 0 297
315
P 0. 5 315
511
P 1. 5/ R 511
514
P 0. 5/ R 514
Response at end of treatment
Reazzjoni mal- waqfa tat - trattament
Sustained response
Reazzjoni sostnuta
P 1.5 PegIntron 1.5 micrograms/kg P 1.0 PegIntron 1.0 microgram/kg P 0.5 PegIntron 0.5 microgram/kg I Interferon alfa-2b 3 MIU P 1.5/R P 0.5/R I/R * **
P 1. 5 PegIntron 1. 5 mikrogrammi/ kg P 1. 0 PegIntron 1. 0 mikrogramma/ kg P 0. 5 PegIntron 0. 5 mikrogramma/ kg I Interferon alfa- 2b 3 MIU P 1. 5/ R P 0. 5/ R I/ R * **
Peg Intron (1.5 micrograms/kg) + ribavirin (800 mg) PegIntron (1.5 to 0.5 microgram/kg) + ribavirin (1,000/1,200 mg) Interferon alfa-2b (3 MIU) + ribavirin (1,000/1,200 mg) p< 0.001 P 1.5 vs.
PegIntron (1. 5 mikrogrammi/ kg) + ribavirin (800 mg) PegIntron (1. 5 sa 0. 5 mikrogramma/ kg) + ribavirin (1, 000/ 1, 200 mg) Interferon alfa- 2b (3 MIU) + ribavirin (1, 000/ 1, 200 mg) p < 0. 001 P 1. 5 vs.
I p = 0.0143 P 1.5/R vs.
I p = 0. 0143 P 1. 5/ R vs.
Sustained response rates with PegIntron + ribavirin (by ribavirin dose, genotype and viral load)
Rati ta ’ risponsi sostnuti b 'PegIntron + ribavirin (bid- doża ta ’ ribavirin, ġenotip u viral load)
HCV Genotype
HCV Ġenotip
Ribavirin dose (mg/kg)
Doża ta ’ P 1. 5/ R P 0. 5/ R Rebetol (mg/ kg)
All ≤ 10.6 > 10.6
Kollha ≤ 10. 6 > 10. 6
Genotype 1 ≤ 600,000 IU/ml
Ġenotip 1 ≤ 600, 000 IU/ ml
Genotype 1 > 600,000 IU/ml
Ġenotip 1
All ≤ 10.6 > 10.6
Kollha ≤ 10. 6
All ≤ 10.6
Kollha ≤ 10. 6 > 10. 6
P 1.5/R P 0.5/R I/R
P 1. 5/ R P 0. 5/ R I/ R
Peg Intron (1.5 micrograms/kg) + ribavirin (800 mg) PegIntron (1.5 to 0.5 microgram/kg) + ribavirin (1,000/1,200 mg) Interferon alfa-2b (3 MIU) + ribavirin (1,000/1,200 mg)
PegIntron (1. 5 mikrogrammi/ kg) + ribavirin (800 mg) PegIntron (1. 5 to 0. 5 mikrogramma/ kg) + ribavirin (1, 000/ 1, 200 mg) Interferon alfa- 2b (3 MIU) + ribavirin (1, 000/ 1, 200 mg)
In the PegIntron monother apy study, the Quality of Life was generally less affected by 0.5 microgram/kg of PegIntron than by either 1.0 microgram/kg of PegIntron once weekly or 3 MIU of interferon alfa-2b three times a week.
Fl- istudju fejn ingħatat monoterapija b 'PegIntron, il- Kwalità tal- Ħajja kienet ġeneralment inqas affettwata b’ 0. 5 mikrogramma/ kg ta ’ PegIntron milli jew b’ 1. 0 mikrogramma/ kg ta ’ PegIntron darba fil- ġimgħa jew b’ 3 MIU ta ’ interferon alfa- 2b tliet darbiet fil- ġimgħa.
In a separate trial, 224 patients with genotype 2 or 3 received PegIntron, 1.5 microgram/kg subcutaneously, once weekly, in combination with ribavirin 800 mg –1,400 mg p.o. for 6 months (based on body weight, only three patients weighing > 105 kg, received the 1,400 mg dose) (Table 7).
Fi prova separata, 224 pazjent b’ ġenotip 2 jew 3 irċevew PegIntron, 1. 5 mikrogrammi/ kg minn taħt il - ġilda, darba fil- ġimgħa, f’ kombinazzjoni ma ’ ribavirin 800 mg- 1, 400 mg p. o. għal 6 xhur (ibbażat fuq il - piż tal- ġisem, tlett pazjenti biss kienu jiżnu > 105 kg, irċevew doża ta ’ 1, 400 mg) (Tabella 7).
Twenty-four% had bridging fibrosis or cirrhosis (Knodell 3/4).
Erbgħa u għoxrin% kellhom fibrożi bridging jew ċirrożi (Knodell 3/ 4).
Virologic Response at End of Treatment, Sustained Virologic Response and Relapse by HCV Genotype and Viral Load* PegIntron 1.5 μg/kg once weekly plus Ribavirin 800-1,400 mg/day
Tabella 7 Rispons viroloġiku fi Tmiem il- kura, Rispons Viroloġiku Sostnut u Irkadar b’ Ġenotip HCV u Viral Load. * PegIntron 1. 5 μg/ kg darba fil- ġimgħa ma ’ Ribavirin 800- 1, 400 mg/ jum
of Treatment Response
Tmiem ir- Rispons tal - Kura
Sustained Virologic Response
Rispons Viroloġiku Sostnut
Relapse
Irkadar
All Subjects
L- individwi kollha
HCV 2 ≤ 600,000 IU/ml
HCV 2 ≤ 600, 000 IU/ ml
> 600,000 IU/ml
> 600, 000 IU/ ml
≤ 600,000 IU/ml
≤ 600, 000 IU/ ml
* Any subject with an undetectable HCV-RNA level at the Follow-Up Week 12 visit and missing data at the Follow- Up Week 24 visit was considered a susta ined responder.
Żjara ma ’ Ġimgħa 24 kienet meqjusa bħala rispons sostnut.
Any subject with missing data in and after the Follow-Up Week 12 window was considered to be a non-responder at Week 24 of follow-up.
Kwalunkwe individwu b’ dejta nieqsa sa ’ u wara l- medda tal- Follow- Up ta ’ Ġimgħa 12 kien meqjus bħala li ma weriex rispons fil- follow- up ta ’ Ġimgħa 24
49%.
Il- kura ta ’ 6 xhur f’ din il- prova kien tollerat aħjar mill- kura ta ’ sena fil- prova bil- kombinazzjoni pivitali, għal twaqqif 5% vs 14%, għal bidla fid- doża 18% vs 49%.
In a non-comparative trial, 235 patients with genotype 1 and low viral load (< 600,000 IU/ml) received PegIntron, 1.5 microgram/kg subcutaneously, once weekly, in combination with weight adjusted ribavirin.
Fi prova mhux kumparattiva, 235 pazjent b’ ġenotip 1 u viral load baxx (< 600, 000 IU/ ml) irċevew PegIntron, 1. 5 mikrogrammi/ kg minn taħt il- ġilda, darba fil- ġimgħa, flimkien ma ’ ribavirin aġġustat skond il- piż.
The overall sustained response rate after a 24-week treatment duration was 50%.
Ir- rata globali tar- rispons sostnut wara 24 ġimgħa ta ’ kura kienet 50%.
Forty-one percent of subjects (97/235) had nondetectable plasma HCV-RNA levels at Week 4 and Week 24 of therapy.
Wieħed u erbgħin ta ’ l - individwi (97/ 235) kellhom livelli ta ’ HCV- RNA fil- plażma li ma jitkejlux f’ Ġimgħa 4 u Ġimgħa 24 tat - terapija.
In this subgroup, there was a 92% (89/97) sustained virological response rate.
F’ dan is- sottogrupp, kien hemm rata ta ’ rispons viroloġiku sostnut ta ’ 92% (89/ 97).
The high sustained response rate in this subgroup of patients was identified in an interim analysis (n=49) and prospectively confirmed (n=48).
Ir- rata għolja ta ’ rispons sostnut f’ dan is- sottogrupp ta ’ pazjenti instab f’ analiżi interim (n=49) u kien ikkonfermat b’ mod prospettiv (n=48).
Limited historical data indicate that treatment for 48 weeks might be associated with a higher sustained response rate (11/11) and with a lower risk of relapse (0/11 as compared to 7/96 following 24 weeks of treatment).
Tgħarif limitat mill- passat jindika li l- kura għal 48 ġimgħa tista ’ tkun assoċjata ma ’ rata ogħla ta ’ rispons (11/ 11) u b’ riskju anqas ta ’ irkadar (0/ 11 meta mqabbel ma ’ 7/ 96 wara 24 ġimgħa ta ’ kura).
Predictability of sustained virological response – Naïve patients Virological reponse by week 12, defined as a 2-log viral load decrease or undetectable levels of HCV- RNA has been shown to be predictive for sustained response (Table 8).
Tbassir ta ’ rispons viroloġiku sostnut - Pazjenti li qatt ma kienu ħadu din il- kura qabel Rispons viroloġiku sat- tnax- il ġimgħa, mfissra bħala tnaqqis ta ’ 2- log fil- viral load jew livelli ta ’ HCV RNA li ma jitkejlux intweriet li tista ’ tintuża biex jitbassar ir- rispons sostnut (Tabella 8) Table 8
sustained response by viral response at week 12 and genotype*
Tbassir ta ’ rispons sostnut permezz ta ’ reazzjoni virali sat- tnax- il ġimgħa u ġenotip *
Treatment PegIntron 1.5 + ribavirin (> 10.6 mg/kg) 48-week treatment PegIntron 1.5 +
Kura PegIntron 1. 5 + ribavirin (> 10. 6 mg/ kg)
Viral response Sustained response Negative predictive value at week 12 1 Yes 75% (82/110) 71% (58/82) ---- No 25% (28/110) 0% (0/28) 100%
Ġinotip Rispons viroloġiku Rispons sostnut Valur negattiv ma ’ ġimgħa 12 imbassar 1 Iva 75% (82/ 110) 71% (58/ 82) ---- Le 25% (28/ 110) 0% (0/ 28) 100%
ribavirin 800-1,400 mg
ġimgħa ta ’ kura 48 PegIntron 1. 5 + ribavirin 800- 1, 400 mg
2 and 3
2 and 3
Yes 99% (213/215) 83% (177/213)
Iva 99% (213/ 215)
24-week treatment
24- week treatment
No 1% (2/215) 50% (1/2)
Le 1% (2/ 215)
* reflects patients with 12 week data available
* jirrifletti pazjenti li għandhom dejta ta ’ 12- il gimgħa
The negative predictive value for sustained response in patients treated with PegIntron in monotherapy was 98%.
Il- valur negattiv li jbassar għal rispons sostnut f’ pazjenti li ġew trattati b 'PegIntron f’ monoterapija kien ta ’ 98%.
HCV/HIV Co-infected patients Two trials have been conducted in patients co-infected with HIV and HCV.
Pazjenti infettati fl- istess ħin b’ HCV/ HIV Saru żewġ provi f’ pazjenti infettati fl- istess ħin b’ HIV u HCV.
The response to treatment in both of these trials is presented in Table 9.
Ir- rispons għall- kura f’ dawn iż- żewġ provi jidher f’ Tabella 9.
Study 1 (RIBAVIC; P01017) was a randomized, multicentre study which enrolled 412 previously untreated adult patients with chronic hepatitis C who were co-infected with HIV.
Studju 1 (RIBAVIC; P01017) kien studju multiċentriku randomized li fih ħadu sehem 412 pazjent adult li ma kienux ikkurati qabel b’ epatite C kronika li kellhom ukoll infezzjoni b’ HIV.
Patients were randomized to receive either PegIntron (1.5 µg/kg/week) plus ribavirin (800 mg/day) or interferon alfa-2b (3 MIU TIW) plus ribavirin (800 mg/day) for 48 weeks with a follow-up period of 6 months.
Il- pazjenti kienu randomized sabiex jirċievu PegIntron (1. 5 µg/ kg/ ġimgħa) ma ’ ribavirin (800 mg/ jum) jew interferon alfa- 2b (3 MIU TIW) ma ’ ribavirin (800 mg/ jum) għal 48 ġimgħa b’ perijodu ta ’ follow- up ta ’ 6 xhur.
Study 2 (P02080) was a randomized, single centre study that enrolled 95 previously untreated adult patients with chronic hepatitis C who were co- infected with HIV.
Studju 2 (P02080) kien randomized, f’ ċentru wieħed li fih ħadu sehem 95 pazjent adult li ma kienux ikkurati qabel b’ epatite C kronika li kellhom l- HIV fl- istess ħin.
Patients were randomized to receive either PegIntron (100 or 150 µg /week based on weight) plus ribavirin (800-1,200 mg/day based on weight) or interferon alfa-2b (3 MIU TIW) plus ribavirin (800-1,200 mg/day based on weight).
Il- pazjenti kienu randomized biex jirċievu PegIntron (100 jew 150 µg/ ġimgħa skond il- piż) ma ’ ribavirin (800- 1, 200 mg/ jum skond il- piż) jew interferon alfa- 2b (3 MIU TIW) ma ’ ribavirin (800- 1, 200 mg/ jum skond il- piż).
The duration of therapy was 48 weeks with a follow-up period of 6 months except for patients infected with genotypes 2 or 3 and viral load < 800,000 IU/ml (Amplicor) who were treated for 24 weeks with a 6-month follow-up period.
It- tul tat- terapija kien 48 ġimgħa bi perijodu ta ’ follow- up ta ’ 6 xhur ħlief għall- pazjenti infettati b’ ġenotip 2 jew 3 u viral load < 800, 000 IU/ ml (Ampiclor) li kienu ikkurati għal 24 ġimgħa bi perijodu follow- up ta ’ 6 xhur.
18 Table 9
Tabella 9
Sustained virological response based on genotype after PegIntron in combination with Ribavirin in HCV/HIV Co-infected patients Study 11 Study 22 PegIntron Interferon PegIntron Interferon (100 or alfa-2b (1.5 µg/kg/ alfa-2b 150c µg/week) (3 MIU TIW) week) + (3 MIU TIW) + + ribavirin + ribavirin
Rispons viroloġiku sostnut ibbażat fuq il- ġenotip wara PegIntron f’ kombinazzjoni ma ’ Ribavirin f’ pazjenti infettati fl- istess ħin b’ HCV/ HIV Studju 11 Studju 22 PegIntron (100 jew Interferon 150c PegIntron Interferon alfa- 2b µg/ ġimgħa) + (3 MIU TIW) (1. 5 µg/ kg / alfa- 2b ribavirin + ribavirin ġimgħa) + (3 MIU TIW) + valur - ribavirin ribavirin valur - (800 - (800 - pb d a d 1, 200 mg) (800 mg) (800 mg) p 1, 200 mg)
All Genotype 1, 4
Kollha Ġenotip 1, 4
27% (56/205) 20% 17% (21/125)
27% (56/ 205) 20% (41/ 205) 0. 047 44% (23/ 52) 21% (9/ 43) 0. 017 17% (21/ 125) 6% (8/ 129) 0. 006 38% (12/ 32) 7% (2/ 27) 0. 007
MIU = million international units; TIW = three times a week. a: p value based on Cochran-Mantel Haenszel Chi square test. b: p value based on chi-square test. c: subjects < 75 kg received 100 µg/week PegIntron and subjects ≥ 75 kg received 150 µg/week PegIntron. d: ribavirin dosing was 800 mg for patients < 60 kg, 1,000 mg for patients 60-75 kg, and 1,200 mg for patients > 75 kg.
MIU =miljun unitajiet internazzjonali; TIW = tlett darbiet fil- ġimgħa. a: valur- p ibbażat fuq it- test Cochran- Mantel Haenszel Chi square. b: valur- p ibbażat fuq it- test chi- square. c: individwi < 75 kg irċevew 100 µg/ ġimgħa PegIntron u individwi ≥ 75 kg irċevew 150 µg/ ġimgħa PegIntron. d: għall- pazjenti < 60 kg ingħataw dożi ta ’ 800 mg ribavirin, 1, 000 mg għall- pazjenti 60- 75 kg, u 1, 200 mg għall- pazjenti > 75 kg.
Histological response Liver biopsies were obtained before and after treatment in Study 1 and were available for 210 of the 412 subjects (51%).
Rispons ħistoloġiku Bijopsiji tal- fwied ittieħdu qabel u wara l- kura fi Studju 1 u kienu disponibbli għal 210 mill - 412 individwu (51%).
Both the Metavir score and Ishak grade decreased among subjects treated with PegIntron in combination with ribavirin.
Kemm il- punteġġ Metavir u l- grad Ishak naqsu fost l- individwi ikkurati b’ PegIntron f’ kombinazzjoni ma ’ ribavirin.
This decline was significant among responders (-0.3 for Metavir and -1.2 for Ishak) and stable (-0.1 for Metavir and -0.2 for Ishak) among non-responders.
Dan it- tnaqqis kien sinifikanti fost dawk li wrew rispons (- 0. 3 għal Metavir u - 1. 2 għal Ishak) u stabbli (- 0. 1 għal Metavir u - 0. 2 għal Ishak) fost dawk li ma kellhomx rispons.
In terms of activity, about one-third of sustained responders showed improvement and none showed worsening.
Mill- lat ta ’ attività, madwar terz ta ’ dawk li kellhom rispons sostnut urew titjib ħadd ma mar għall- agħar.
There was no improvement in terms of fibrosis observed in this study.
Ma deherx titjib mill- lat ta ’ fibrożi f’ dan l- istudju.
Steatosis was significantly improved in patients infected with HCV Genotype 3.
Stejatożi tjiebet b’ mod sinifikanti f’ pazjenti infettti b’ HCV ta ‘ Ġenotip 3.
PegIntron/ribavirin retreatment of prior treatment failures In a non-comparative trial, 2,293 patients with moderate to severe fibrosis who failed previous treatment with combination alpha interferon/ribavirin were retreated with PegIntron, 1.5 microgram/kg subcutaneously, once weekly, in combination with weight adjusted ribavirin.
Kura mill- ġdid b’ PegIntron/ ribavirin ta ’ każijiet fejn kuri li kienu ngħataw qabel fallew Fi prova mhux kumparattiva, 2, 293 pazjent b’ fibrożi moderata għal severa li kienu fallew għall- kura li ngħataw qabel b’ taħlita ta ’ interferon alfa/ ribavirin kienu kkurati mill- ġdid b’ PegIntron, 1. 5 mikrogramma/ kg minn taħt il- ġilda, darba fil- ġimgħa, flimkien ma ’ ribavirin mogħti skond il- piż tal - ġisem.
Failure to prior therapy was defined as relapse or non-response (HCV-RNA positive at the end of a minimum of 12 weeks of treatment).
Falliment għal terapija li tkun ngħatat qabel kien definit bħala irkadar jew nuqqas ta rispons (HCV - RNA pożittivi fi tmiem ta ’ mill- anqas 12- il ġimgħa ta ’ kura).
Patients who were HCV-RNA negative at Treatment Week 12 continued treatment for 48 weeks and were followed for 24 weeks post-treatment.
Pazjenti li kienu HCV- RNA negattivi fit- 12- il Ġimgħa tal- Kura komplew il- kura għal 48 ġimgħa u kienu segwiti għal 24 ġimgħa wara l- kura.
Response Week 12 was defined as undetectable HCV- RNA after 12 weeks of treatment.
Rispons f’ Ġimgħa 12 kien definit bħala HCV- RNA li ma setgħux jitkejlu wara 12- il ġimgħa ta ’ kura.
Sustained Virologic Response (SVR) is defined as undetectable HCV-RNA at 24 weeks post-treatment (Table 10).
Rispons Viroloġiku Sostnut (SVR) huwa definit bħala HCV - RNA li ma jistgħux jitkejlu ma ’ l- 24 ġimgħa wara l- kura (Tabella 10).
19 Table 10 Rates of Response to retreatment in prior treatment failures
Tabella 10 Rati ta ’ Rispons għall- kura mill- ġdid f’ Każijiet fejn il- Kura Qabel kienet falliet
Patients with undetectable HCV–RNA at treatment Week 12 and SVR upon retreatement Overall
Pazjenti b’ HCV– RNA li ma setgħax jitkejjel f’ Ġimgħa tal- Kura 12 u SVR wara kura mill- ġdid Popolazzjoni
interferon alpha/ribavirin
interferon alpha/ ribavirin
peginterferon alpha/ribavirin
peginterferon alpha/ ribavirin
Population*
globali *
Response Week 12% (n/N)
SVR% (n/ N) 99% CI
Response SVR% (n/ N) Week 12% 99% CI (n/N)
Response SVR% (n/ N) Week 12% 99% CI (n/ N)
Overall Prior Response
B’ mod globali Rispons Qabel
38.6 (549/1,423) 59.4 (326/549) 54.0,64.8
38. 6 (549/ 1, 423) 59. 4 (326/ 549) 54. 0, 64. 8
31.5 (272/863) 50.4 (137/272) 42.6, 58.2
31. 5 (272/ 863) 50. 4 (137/ 272) 42. 6, 58. 2
21.7 (497/2,293) 19.5, 23.9
21. 7 (497/ 2, 293) 19. 5, 23. 9
Relapse
Jirkadu
67.7 (203/300) 59.6 (121/203) 50.7, 68.5
67. 7 (203/ 300) 59. 6 (121/ 203) 50. 7, 68. 5
58.1 (200/344) 52.5 (105/200) 43.4, 61.6
58. 1 (200/ 344) 52. 5 (105/ 200) 43. 4, 61. 6
37.7 (243/645) 32.8, 42.6
37. 7 (243/ 645) 32. 8, 42. 6
Genotype 1/4
Ġenotip 1/ 4
59.7 (129/216) 51.2 (66/129) 39.8, 62.5
59. 7 (129/ 216) 51. 2 (66/ 129) 39. 8, 62. 5
48.6 (122/251) 44.3 (54/122) 32.7, 55.8
48. 6 (122/ 251) 44. 3 (54/ 122) 32. 7, 55. 8
28.6 (134/468) 23.3, 34.0
28. 6 (134/ 468) 23. 3, 34. 0
88.9 (72/81)
88. 9 (72/ 81)
73.6 (53/72) (60.2, 87.0)
73. 6 (53/ 72) (60. 2, 87. 0)
83.7 (77/92)
83. 7 (77/ 92)
64.9 (50/77) 50.9, 78.9
64. 9 (50/ 77) 50. 9, 78. 9
61.3 (106/173) 51.7, 70.8
61. 3 (106/ 173) 51. 7, 70. 8
28.6 (258/903)
28. 6 (258/ 903)
57.0 (147/258) 49.0, 64.9
57. 0 (147/ 258) 49. 0, 64. 9
12.4 (59/476)
12. 4 (59/ 476)
44.1 (26/59) 27.4, 60.7
44. 1 (26/ 59) 27. 4, 60. 7
13.6 (188/1,385) 11.2, 15.9
13. 6 (188/ 1, 385) 11. 2, 15. 9
23.0 (182/790)
23. 0 (182/ 790)
51.6 (94/182) 42.1, 61.2
51. 6 (94/ 182) 42. 1, 61. 2
9.9 (44/446)
9. 9 (44/ 446)
38.6 (17/44) 19.7, 57.5
38. 6 (17/ 44) 19. 7, 57. 5
9.9 (123/1,242) 7.7, 12.1
9. 9 (123/ 1, 242) 7. 7, 12. 1
Genotype 2/3 Genotype
Ġenotip 2/ 3 Ġenotip
67.9 (74/109)
67. 9 (74/ 109)
70.3 (52/74) 56.6, 84.0
70. 3 (52/ 74) 56. 6, 84. 0
53.6 (15/28)
53. 6 (15/ 28)
60.0 (9/15) 27.4, 92.6
60. 0 (9/ 15) 27. 4, 92. 6
46.0 (63/ 137) 35.0, 57.0
46. 0 (63/ 137) 35. 0, 57. 0
30.2 (343/1,135)
30. 2 (343/ 1, 135)
51.3 (176/343) 44.4, 58.3
51. 3 (176/ 343) 44. 4, 58. 3
23.0 (162/704)
23. 0 (162/ 704)
42.6 (69/162) 32.6, 52.6
42. 6 (69/ 162) 32. 6, 52. 6
14.6 (270/1,846) 12.5, 16.7
14. 6 (270/ 1, 846 12. 5, 16. 7
77.1 (185/240)
77. 1 (185/ 240)
73.0 (135/185) 64.6, 81.4
73. 0 (135/ 185) 64. 6, 81. 4
75.6 (96/127)
75. 6 (96/ 127)
63.5 (61/96) 50.9, 76.2
63. 5 (61/ 96) 50. 9, 76. 2
55.3 (203/367) 48.6, 62.0
55. 3 (203/ 367) 48. 6, 62. 0
4 METAVIR Fibrosis score
4 Punteġġ Fibrożi METAVIR
42.5 (17/40)
42. 5 (17/ 40)
70.6 (12/17) 42.1, 99.1
70. 6 (12/ 17) 42. 1, 99. 1
44.4 (12/27)
44. 4 (12/ 27)
50.0 (6/12) 12.8, 87.2
50. 0 (6/ 12) 12. 8, 87. 2
28.4 (19/67) 14.2, 42.5
28. 4 (19/ 67) 14. 2, 42. 5
46.0 (193/420)
46. 0 (193/ 420)
66.8 (129/193) 58.1, 75.6
66. 8 (129/ 193) 58. 1, 75. 6
33.6 (78/232)
33. 6 (78/ 232)
57.7 (45/78) 43.3, 72.1
57. 7 (45/ 78) 43. 3, 72. 1
29.2 (191/653) 24.7, 33.8
29. 2 (191/ 653) 24. 7, 33. 8
38.0 (163/429)
38. 0 (163/ 429)
62.6 (102/163) 52.8, 72.3
62. 6 (102/ 163) 52. 8, 72. 3
32.4 (78/241)
32. 4 (78/ 241)
51.3 (40/78) 36.7, 65.9
51. 3 (40/ 78) 36. 7, 65. 9
21.9 (147/672) 17.8, 26.0
21. 9 (147/ 672) 17. 8, 26. 0
F4 Baseline Viral Load
F4 Linja bażi tat - tgħabija virali
33.6 (192/572)
33. 6 (192/ 572)
49.5 (95/192) 40.2, 58.8
49. 5 (95/ 192) 40. 2, 58. 8
29.7 (116/390)
29. 7 (116/ 390)
44.8 (52/116) 32.9, 56.7
44. 8 (52/ 116) 32. 9, 56. 7
16.5 (159/966) 13.4, 19.5
16. 5 (159/ 966) 13. 4, 19. 5
HVL (> 600,000 IU/ml)
HVL (> 600, 000 IU/ ml)
32.4 (280/864)
32. 4 (280/ 864)
56.1 (157/280) 48.4, 63.7
56. 1 (157/ 280) 48. 4, 63. 7
26.5 (152/573)
26. 5 (152/ 573)
41.4 (63/152) 31.2, 51.7
41. 4 (63/ 152) 31. 2, 51. 7
16.6 (239/1,441) 14.1, 19.1
16. 6 (239/ 1, 441) 14. 1, 19. 1
48.3 (269/557)
48. 3 (269/ 557)
62.8 (169/269) 55.2, 70.4
62. 8 (169/ 269) 55. 2, 70. 4
41.0 (118/288)
41. 0 (118/ 288)
61.0 (72/118) 49.5, 72.6
61. 0 (72/ 118) 49. 5, 72. 6
30.2 (256/848) 26.1, 34.2
30. 2 (256/ 848) 26. 1, 34. 2
Non-responder defined as serum/plasma HCV-RNA positive at the end of a minimum of 12 weeks of treatment.
Ma wrewx rispons definit bħala HCV- RNA fis- serum/ plażma pożittiv fi tmiem it- 12- il ġimgħa ta ’ kura.
Plasma HCV-RNA is measured with a research-based quantitative polymerase chain reaction assay by a central laboratory *Intent to treat population includes 7 patients for whom at least 12 weeks of prior therapy could not be confirmed.
HCV- RNA fil- plażma jitkejjel b’ essej ta ’ reazzjoni ta ’ katina tal- polymeras kwantitattiv ibbażat fuq riċerka minn laboratorju ċentrali. * Popolazzjoni bl- intenzjoni li tiġi ikkurata tinkludi 7 pazjenti li għalihom mill- anqas 12- il ġimgħa ta ’ terapija minn qabel ma setgħetx tkun ikkonfermata.