qanastek/EMEA-V3 huggingface dataset:
Use with ribavirin Significant teratogenic and/ or embryocidal effects have been demonstrated in all animal species exposed to ribavirin.
L- użu ma ’ ribavirin Effetti teratoġeniċi sinifikanti u/ jew effetti embrijoċidi dehru f’ kull speċji ta ’ annimal li kien espost għal ribavirin.
Ribavirin therapy is contraindicated in women who are pregnant.
Terapija b’ ribavirin hija kontra- indikata għal nisa waqt it- tqala.
Extreme care must be taken to avoid pregnancy in female patients or in partners of male patients taking Pegasys in combination with ribavirin.
Għandu jkun hemm attenzjoni kbira biex ma jkunx hemm tqala ta ’ pazjenti nisa jew ta ’ sieħba ta ’ pazjenti rġiel li qed jieħdu Pegasys f’ taħlita ma ’ ribavirin.
Female patients of childbearing potential and their partners must each use an effective contraceptive during treatment and for 4 months after treatment has been concluded.
Pazjenti nisa li jistgħu jinqabdu tqal u s- sieħeb tagħhom iridu jużaw kontraċettiv effettiv kull wieħed waqt il- kura u għal 4 xhur wara li tkun intemmet il- kura.
Male patients and their female partners must each use an effective contraceptive during treatment and for 7 months after treatment has been concluded.
Pazjenti rġiel u sieħba femminili tagħhom iridu jużaw kontraċettiv effettiv kull wieħed waqt il- kura u għal 7 xhur wara li tkun intemmet il- kura.
Please refer to the ribavirin SPC.
Jekk jogħġbok ara l- SPC ta ’ ribavirin.
Pegasys has a minor or moderate influence on the ability to drive and use machines.
Pegasys għandu effett żgħir jew moderat fuq il- ħila biex issuq u tħaddem magni.
Patients who develop dizziness, confusion, somnolence or fatigue should be cautioned to avoid driving or operating machinery.
Pazjenti li jiżviluppaw sturdament, konfużjoni, ngħas jew għeja għadhom ikunu avżati sabiex jevitaw li jsuqu jew iħaddmu xi magni.
Experience from clinical trials
Esperjenza minn provi kliniċi
Chronic hepatitis C
Epatite Ċ kronika
The frequency and severity of the most commonly reported adverse reactions with Pegasys are similar to those reported with interferon alfa-2a (see Table 4).
Il- frekwenza u s- severità tar- reazzjonijiet avversi li dehru l- aktar ta ’ spiss b' Pegasys huma simili ħafna għal dawk li dehru b’ interferon alfa- 2a (ara Tabella 4).
The most frequently reported adverse reactions with Pegasys 180 micrograms were mostly mild to moderate in severity and were manageable without the need for modification of doses or discontinuation of therapy.
Ir- reazzjonijiet avversi li dehru l- aktar ta ’ spiss b' Pegasys 180 mikrogramma ġeneralment kienu ħfief għall- moderati fis- severità tagħhom u kienu kontrollati mingħajr ma kien hemm bżonn li tinbidel id- doża jew li titwaqqaf it- terapija.
Chronic hepatitis B
Epatite B kronika
In clinical trials of 48 week treatment and 24 weeks follow-up, the safety profile for Pegasys in chronic hepatitis B was similar to that seen in chronic hepatitis C.
Fi provi kliniċi ta ’ 48 ġimgħa ta ’ kura u 24 ġimgħa ta ’ wara, il- profil ta ’ sigurtà ta ’ Pegasys f’ epatite B kronika kien simili għal dak li deher f’ epatite Ċ kronika.
With the exception of pyrexia the frequency of the majority of the reported adverse reactions was notably less in CHB patients treated with Pegasys monotherapy compared with HCV patients treated with Pegasys monotherapy (see Table 4) Adverse events were experienced by 88% of Pegasys-treated patients as compared with 53% of patients in the lamivudine comparator group, while 6% of the Pegasys-treated and 4% of the lamivudine-treated patients experienced serious adverse events during the studies.
Avvenimenti avversi dehru fi 88% tal- pazjenti kkurati b’ Pegasys meta mqabbel ma ’ 53% tal- pazjenti fil- grupp ta ’ paragun b’ lamivudine, filwaqt li 6% tal- pazjenti kkurati b’ Pegasys u 4% tal - pazjenti kkurati b’ lamivudine esperjenzaw episodji avversi serji waqt l- istudji.
Adverse events or laboratory abnormalities led to 5% of patients withdrawing from Pegasys treatment, while less than 1% of patients withdrew from lamivudine treatment for these reasons.
Avvenimenti avversi jew anormalitajiet tal- laboratorju wasslu għal twaqqif tal- kura b’ Pegasys f’ 5% tal- pazjenti, filwaqt li anqas minn 1% tal- pazjenti waqfu mill- kura b’ lamivudine għal dawn ir- raġunijiet.
The percentage of patients with cirrhosis who withdrew from treatment was similar to that of the overall population in each treatment group.
Il- persentaġġ ta ’ pazjenti b’ ċirrożi li waqfu mill- kura kien simili għal dak tal- popolazzjoni globali f’ kull grupp ta ’ kura.
Chronic hepatitis C in prior non-responder patients
Epatite Ċ kronika f’ pazjenti li ma rrispondewx qabel
Overall, the safety profile for Pegasys in combination with ribavirin in prior non-responder patients was similar to that in naïve patients.
Globalement, f’ pazjenti li ma rrispondewx qabel, il- profil ta ’ sigurtà ta ’ Pegasys flimkien ma ’ ribavirin kien simili għal dak ta ’ pazjenti li qatt ma kienu ħadu kura qabel.
In a clinical trial of non-responder patients to prior pegylated interferon alfa-2b/ ribavirin, which exposed patients to either 48 or 72 weeks of treatment, the frequency of withdrawal for adverse events or laboratory abnormalities from Pegasys treatment and
Fi prova klinika ta ’ pazjenti li ma rrispondewx għal pegylated interferon alfa- 2b/ ribavirin mogħti qabel, li esponiet il- pazjenti għal 48 jew 72 ġimgħa ta ’ kura, il- frekwenza ta ’ waqfien minħabba avvenimenti avversi jew anormalitajiet tal - laboratorju kkawżati minn kura ta ’ Pegasys u kura ta ’ ribavirin kienet 6% u 7% rispettivament, fil - gruppi ta ’ 48 ġimgħa u 12% u 13% rispettivament, fil- gruppi ta ’ 72 ġimgħa.
Similarly for patients with cirrhosis or transition to cirrhosis, the frequencies of withdrawal from Pegasys treatment and ribavirin treatment were higher in the 72-week treatment arms (13% and 15%) than in the 48-week arms (6% and 6%).
B’ mod simili għall- pazjenti b’ ċirrożi jew li qed jiżviluppaw ċirrożi, il- frekwenza ta ’ waqfien minn kura ta ’ Pegasys u kura ta ’ ribavirin kienet ogħla fil- gruppi ta ’ kura ta ’ 72 ġimgħa (13% u 15%) meta mqabbel mal- ġruppi ta ’ 48 ġimgħa (6% u 6%).
Patients who withdrew from previous therapy with pegylated interferon alfa-2b/ ribavirin because of hematological toxicity were excluded from enrolling in this trial.
Pazjenti li waqfu terapija ta ’ qabel b’ pegylated interferon alfa- 2b/ ribavirin minħabba t- tossiċità ematoloġika kienu esklużi minn din il- prova.
In another clinical trial, non-responder patients with advanced fibrosis or cirrhosis (Ishak score of 3 to 6) and baseline platelet counts as low as 50,000/ mm3 were treated for 48 weeks.
Fi prova klinika oħra, pazjenti b’ fibrożi jew ċirrożi avvanzata li ma rrispondewx (punteġġ Ishak ta ’ 3 sa 6) u għadd tal- plejtlits fil- linja bażi baxx sa 50, 000/ mm3 kienu kkurati għal 48 ġimgħa.
Haematologic laboratory abnormalities observed during the first 20 weeks of the trial included anemia (26% of patients experienced a hemoglobin level of < 10 g/ dL), neutropenia (30% experienced an ANC < 750/ mm3), and thrombocytopenia (13% experienced a platelet count < 50,000/ mm3) (see section 4.4).
Anormalitajiet ematoloġiċi tal- laboratorju osservati waqt l- ewwel 20 ġimgħa tal- prova kienu jinkludu anemija (26% tal- pazjenti kellhom livell ta ’ l- emoglobina ta ’ < 10 g/ dL), newtropenija (30% kellhom ANC < 750/ mm3), u tromboċitopenija (13% kellhom għadd tal- plejtlits < 50, 000 / mm3) (ara sezzjoni 4. 4).
Chronic hepatitis C and HIV co-infection
Infezzjoni fl- istess ħin b’ epatite Ċ kronika u b’ HIV:
In HIV-HCV co-infected patients, the clinical adverse event profiles reported for Pegasys, alone or in combination with ribavirin, were similar to those observed in HCV mono-infected patients For HIV- HCV patients receiving Pegasys and ribavirin combination therapy other undesirable effects have been reported in ≥ 1% to ≤ 2% of patients: hyperlactacidaemia/ lactic acidosis, influenza, pneumonia, affect lability, apathy, tinnitus, pharyngolaryngeal pain, cheilitis, acquired lipodystrophy and chromaturia.
Għall- pazjenti b’ HIV- HCV li qed jirċievu terapija kombinata b’ Pegasys u ribavirin kienu rrapportati effetti mhux mixtieqa oħra f’ ≥ 1% sa ≤ 2% tal- pazjenti: iperlattiċidemija/ aċidożi lattika, influwenza, pnewmonja, effett fuq il- lijabilità, apatija, tinnitus, uġigħ faringolarinġali, kelite, lipodistrofija miksuba u kromaturja.
Pegasys treatment was associated with decreases in absolute CD4+ cell counts within the first 4 weeks without a reduction in CD4+ cell percentage.
Kura b’ Pegasys kienet assoċjata ma ’ tnaqqis fl- għadd assolut ta ’ ċelloli CD4+ fl- ewwel 4 ġimgħat mingħajr tnaqqis fil- persentaġġ taċ- ċelloli CD4+.
The decrease in CD4+ cell counts was reversible upon dose reduction or cessation of therapy.
It- tnaqqis fl- għadd taċ- ċelloli CD4+ kien riversibbli hekk kif tnaqqset id- doża jew twaqqfet it- terapija.
The use of Pegasys had no observable negative impact on the control of HIV viraemia during therapy or follow-up.
L- użu ta ’ Pegasys ma kellu l- ebda impatt negattiv li seta jiġi osservat fuq il- kontroll tal- viremija ta ’ HIV waqt it- terapija jew wara.
Limited safety data (N= 51) are available in co- infected patients with CD4+ cell counts < 200/ µl.
Tagħrif limitat dwar is- sigurtà (N= 51) huwa disponibbli f’ pazjenti ko- infettati b’ għadd ta ’ ċelloli ta ’ CD4+ < 200/ µl.
Table 4 summarises the undesirable effects reported with Pegasys monotherapy in CHB or CHC patients and with Pegasys in combination with ribavirin in CHC patients.
Tabella 4 tiġbor l- effetti mhux mixtieqa rrappurati b’ monoterapija ta ’ Pegasys f’ pazjenti b’ CHB jew CHC u b’ Pegasys f’ taħlita flimkien ma ’ ribavirin f’ pazjenti b’ CHC.
Table 4:
13 Tabella 4:
Undesirable Effects Reported with Pegasys Monotherapy for HBV or HCV or In Combination with Ribavirin for HCV Patients Body system
Effetti Mhux Mixtieqa Irrapportati b’ Monoterapija b’ Pegasys għal HBV jew HCV jew f’ Taħlita ma ’ Ribavirin għall- Pazjenti b’ HCV Sistema tal - ġisem Infezzjonijiet u infestazzjonijiet
Very Common ≥ 1/ 10
Komuni Ħafna ≥ 1/ 10
Common ≥ 1/ 100 to < 1/ 10
Komuni ≥ 1/ 100 sa < 1/ 10 Infezzjoni tas - sistema respiratorja ta ’ fuq, bronkite, kandidajiżi fil - ħalq, herpes simplex, infezzjonijiet mill- moffa, virali u mill- batterja
Uncommon ≥ 1/ 1000 to < 1/ 100
Mhux komuni ≥ 1/ 1000 sa < 1/ 100 Pnewmonja, infezzjoni tal - ġilda
Rare ≥ 1/ 10,000 to < 1/ 1000
Rari ≥ 1/ 10, 000 sa < 1/ 1000 Endokardite, otite esterna
Very rare < 1/ 10,000
Rari ħafna < 1/ 10, 000
Infections and infestations
Neoplażmi beninni u malinni
Hepatic neoplasm
Neoplażma epatika
Blood and lymphatic system disorders
Disturbi tad - demm u tas - sistema limfatika
Thrombocytopenia, anaemia, lymphadenopathy
Tromboċitopenja, anemija, limfo - adenopatija
Pancytopenia
Panċitopenja
Aplastic anemia
Anemija aplastika
Sarcoidosis, thyroiditis
Sarkojdożi, tirojdite
Anaphylaxis, systemic lupus erythematosus, rheumatoid arthritis
Anafilassi, lupus erythematosus sistemika, artrite rewmatojda
Idiopathic or thrombotic thrombocytopenic purpura
Purpura tromboċitopenika idjopatika jew trombotika
Endocrine disorders
Disturbi fis - sistema endokrinarja
Hypothyroidism, hyperthyroidism
Ipotajrojdiżmu, ipertajrojdiżmu
Diabetes
Dijabete
Diabetic ketoacidosis
Ketoaċidożi dijabetika
13 Body system Metabolism and Nutrition Disorders
Disturbi fil - metaboliżmu u n- nutrizzjoni
Common ≥ 1/ 100 to < 1/ 10
Anoressija
Uncommon ≥ 1/ 1000 to < 1/ 100 Dehydration
Deidratazzjoni
Emotional disorders, mood alteration Aggression, nervousness, libido decreased
Depressjoni Disturbi *, ansjetà, emozzjonali, insomnja * tibdil fil- burdata, aggressività, nervi, tnaqqis fil - libido,
Suicidal ideation, hallucinations
Ħsibijiet ta ’ suwiċidju, alluċinazzjonijiet
Suicide, psychotic disorder
Suwiċidju, disturb psikotiku
Memory impairment, syncope, weakness, migraine, hypoaesthesia, hyperaesthesia, paraesthesia, tremor, taste disturbance, nightmares, somnolence
Uġigħ ta ’ Indeboliment fil - ras, memorja, sturdament * sinkope,, tfixkil fil - debbulizza, konċentrazz emigranja, joni ipoestesija, iperestesija, parestesija, tregħid, disturb fit- togħma, inkubi, ngħas
Peripheral neuropathy
Newropatija periferali
Coma, convulsions,, facial palsy
Koma, konvulżjonijiet, paralisi fil- wiċċ
Eye disorders
Disturbi fl - għajnejn
Vision blurred, eye pain, eye inflammation, xerophthalmia
Vista imċajpra, uġigħ fl- għajn, infjammazzjoni ta ’ l- għajn, gżeroftalmja
Retinal hemorrhage
Emorraġija fir - retina
Optic neuropathy, papilledema, retinal vascular disorder, retinopathy, corneal ulcer
Newropatija ottika, Telf tal- vista papilledima, disturbi vaskulari fir- retina, retinopatija, ulċera tal- korneja
Ear and labyrinth disorders
Disturbi fil - widnejn u fis - sistema labirintika
Vertigo, earache
Vertigo, uġigħ fil- widna
Cardiac disorders
14 Sistema tal - ġisem Disturbi fil- qalb
Tachycardia, palpitations, oedema peripheral
Komuni ≥ 1/ 100 sa < 1/ 10 Takikardja, palpitazzjonijiet, edima periferali
Myocardial infarction, congestive heart failure, angina, supraventricular tachycardia, arrhythmia, atrial fibrillation, pericarditis, cardiomyopathy
Rari ≥ 1/ 10, 000 sa < 1/ 1000 Infart mijokardijaku, insuffiċjenza tal- qalb konġestiva, anġina, takikardja supraventrikolari, arritmija, fibrillazzjoni atrijali, perikardite, kardjomijopatija
Flushing
Fwawar
Cerebral haemorrhage, vasculitis
Emorraġija ċerebrali, vaskulite
Dyspnoea, cough
Qtugħ ta ’ nifs, sogħla
Dyspnoea exertional, epistaxis, nasopharyngitis, sinus congestion, nasal congestion, rhinitis, sore throat
Qtugħ ta ’ nifs meta titħabat, epistassi, nażofarinġite, konġestjoni fis - sinus, konġestjoni ta ’ l - imnieħer, rinite, uġigħ fil - griżmejn
Wheezing
Tħarħir
Interstitial pneumonitis including fatal outcome, pulmonary embolism
Pnewmonite interstizjali inkluż riżultat fatali, emboliżmu pulmonari
Diarrhoea*, nausea*, abdominal pain*
Dijarea *, tqalligħ *, uġigħ addominali *
Vomiting, dyspepsia, dysphagia, mouth ulceration, gingival bleeding, glossitis, stomatitis, flatulence, dry mouth
Rimettar, dispepsja, disfaġja, ulċeri fil- ħalq, ħanek inixxi d- demm, infjammazzjoni ta ’ l- ilsien, stomatite, gass, ħalq xott
Gastrointestinal bleeding
Telf ta ’ demm gastro- intestinali
Peptic ulcer, pancreatitis
Ulċera peptika, pankreatite
Hepato-biliary disorders
Disturbi fil - fwied u fil - marrara
Hepatic dysfunction
L- fwied ma jaħdimx normali
Hepatic failure, cholangitis, fatty liver
Insuffiċjenza epatika, kolanġite, fwied xaħmi
Alopecia, dermatitis, pruritis, dry skin
Alopeċja, dermatite, ħakk, ġilda xotta
Rash, sweating increased, psoriasis, urticaria, eczema, skin disorder, photosensitivity reaction, night sweats
Raxx, żieda fl - għaraq, psorjasi urtikarja, ekżema, disturbi fil- ġilda, reazzjoni ta ’ fotosensittività, tgħereq ħafna matul il- lejl
Toxic epidermal necrolysis, Stevens-Johnson syndrome, angioedema, erythema multiforme
Nekrolisi epidermali tossika, Sindrome Stevens - Johnson, anġjoedima, eritema multiforme
Musculoskeletal Myalgia, connective tissue arthralgia and bone disorders
Disturbi muskolu - skeletrali, tal - connective tissue u ta ’ l- għadam
Back pain, arthritis, muscle weakness, bone pain, neck pain, musculoskeletal pain, muscle cramps
Uġigħ fid- dahar, artrite, indebboliment tal- muskoli, uġigħ fl- għadam, uġigħ fl- għonq, uġigħ muskolu - skeletrali, bugħawwieġ fil - muskoli
Myositis
Majosite
Renal and urinary disorders Reproductive system and breast disorders
Disturbi fis - sistema riproduttiva u fis- sider
Renal insufficiency
Rari ħafna < 1/ 10, 000
General disorders Pyrexia, and rigors*, administration pain*, site conditions asthenia, fatigue, injection site reaction*, irritability*
Disturbi ġenerali Deni, u kondizzjonijiet rogħda *, ta 'mnejn uġigħ *, jingħata astenja, għeja, reazzjoni fis- sit ta ’ l - injezzjoni *, irritabilità *
Chest pain, influenza like illness, malaise, lethargy, hot flushes, thirst
Uġigħ fis- sider, mard li jixbaħ l - influwenza, tħossok ma tiflaħx, letarġija, fwawar, għatx
Investigations Injury and poisoning
Ivestigazzjonijiet Korriment u avvelenament
Substance overdose
Doża eċċessiva tas - sustanza
*These adverse reactions were common (≥ 1/ 100 to < 1/ 10) in CHB patients treated with Pegasys monotherapy
* Dawn ir- reazzjonijiet avversi kienu komuni (≥ 1/ 100 sa < 1/ 10) f’ pazjenti b’ CHB kkurati b’ monoterapija ta ’ Pegasys
Post marketing adverse events
Avvenimenti avversi rrapportati wara t- tqegħid fis- suq
Nervous System Disorders:
Disturbi fis- sistema nervuża:
Cerebral ischemia: frequency unknown.
Iskemija ċerebrali: frekwenza mhux magħrufa.
Eye Disorders:
Disturbi fl- għajnejn:
Serous retinal detachment: frequency unknown.
Distakk seruż tar- retina: frekwenza mhux magħrufa.
As with other alpha interferons, serous retinal detachment has been reported with Pegasys.
Bħal b’ alpha interferons oħra, b’ Pegasys kien irrapportat distakk seruż tar- retina.
Musculoskeletal connective tissue and bone disorders:
Disturbi muskolu- skeletrali, tal- connective tissue u tal- għadam:
Rhabdomyolysis: frequency unknown.
Rabdomijolisi: frekwenza mhux magħrufa.
ALT increase, bilirubin increase, electrolyte disturbance (hypokalaemia, hypocalcaemia, hypophosphataemia), hyperglycaemia, hypoglycaemia and elevated triglycerides (see section 4.4.).
Riżultati tal- laboratorju Kura b' Pegasys kienet assoċċjata ma ’ riżultati tal- laboratorju anormali: żieda fl- ALT, żieda fil- bilirubin, disturbi fil- livelli ta ’ l- elektroliti (ipokalimja, ipokalċimja, ipofosfatimja), ipergliċemija, ipogliċemija u livelli għoljin ta ’ trigliċeridi (ara sezzjoni 4. 4).
With both Pegasys monotherapy, and also the combined treatment with ribavirin, up to 2% of patients experienced increased ALT levels that led to dose modification or discontinuation of the treatment.
Kemm fil- monoterapija b' Pegasys, kif ukoll fit- terapija kombinata ma ’ ribavirin, sa 2% mill- pazjenti kellhom żieda fil- livelli tal- ALT li wasslet għat- tibdil fid - doża jew għall- twaqqif tal- kura.
Treatment with Pegasys was associated with decreases in haematological values (leucopenia, neutropenia, lymphopenia, thrombocytopenia and haemoglobin), which generally improved with dose modification, and returned to pre-treatment levels within 4-8 weeks upon cessation of therapy (see sections 4.2 and 4.4).
Kura b' Pegasys kienet assoċjata ma ’ tnaqqis fil- valuri ematoloġiċi (lewkopenja, newtropenja, limfopenja, tromboċitopenja u emoglobina), li ġeneralment marru għall- aħjar b’ tibdil tad- doża, u marru lura għall- livelli ta ’ qabel bdiet il- kura fi żmien 4- 8 ġimgħat wara li waqfet it- terapija (ara sezzjonijiet 4. 2 u 4. 4).
Moderate (ANC:
Newtropenja moderata (ANC:
0.749 - 0.5 x 109/ l) and severe (ANC: < 0.5 x 109/ l) neutropenia was observed respectively in 24% (216/ 887) and 5% (41/ 887) of patients receiving Pegasys 180 micrograms and ribavirin 1000/ 1200 milligrams for 48 weeks.
0. 749 – 0. 5 x 109/ l) u severa (ANC: < 0. 5 x 109/ l) kienet osservata rispettivament f’ 24% (216/ 887) u 5% (41/ 887) tal- pazjenti li rċevew Pegasys 180 mikrogramma u ribavirin 1000/ 1200 milligramma għal 48 ġimgħa.
Anti-interferon antibodies 1-5% of patients treated with Pegasys developed neutralising anti-interferon antibodies.
Antikorpi anti- interferon 1- 5% tal- pazjenti kurati b' Pegasys żviluppaw antikorpi anti- interferon newtralizzanti.
However in neither disease was this correlated with lack of therapeutic response.
Bħal b’ interferons oħra, dehret inċidenza ogħla ta ’ antikorpi newtralizzanti f’ epatite B kronika. Madanakollu, dan ma kienx ikkorrelat ma ’ nuqqas ta ’ rispons terapewtiku fl- ebda marda.
Thyroid function Pegasys treatment was associated with clinically significant abnormalities in thyroid laboratory values requiring clinical intervention (see section 4.4).
Funzjoni tat- tirojde Kura b' Pegasys kienet assoċjata ma ’ anormalitajiet ta ’ sinifikanza klinika fir- riżultati tal- figuri tal - laboratorju tat- tirojde li kellhom bżonn intervent kliniku (ara sezzjoni 4. 4).
The frequencies observed (4.9%) in patients receiving Pegasys/ ribavirin (NV15801) are similar to those observed with other interferons.
Il- frekwenzi osservati (4. 9%) f’ pazjenti li kienu qed jirċievu Pegasys/ ribavirin (NV15801) huma simili għal dawk osservati b’ interferons oħrajn.
Laboratory values for HIV-HCV co-infected patients Although haematological toxicities of neutropenia, thrombocytopenia and anaemia occurred more frequently in HIV-HCV patients, the majority could be managed by dose modification and the use of growth factors and infrequently required premature discontinuation of treatment.
16 Figuri tal - laboratorju f’ pazjenti ko- infettati b’ HIV- HCV Għalkemm tossiċitajiet ematoloġiċi ta ’ newtropenja, tromboċitopenja u anemija seħħew aktar ta ’ spiss f’ pazjenti b’ HIV- HCV, il- maġġoranza setgħet tiġi kkontrollata permezz ta ’ modifikazzjoni fid- doża u l - użu ta ’ fatturi ta ’ tkabbir u f’ każijiet rari kien meħtieġ twaqqif bikri tal- kura.
Decrease in ANC levels below 500 cells/ mm3 was observed in 13% and 11% of patients receiving Pegasys monotherapy and combination therapy, respectively.
Tnaqqis fil- livelli ta ’ ANC taħt 500 ċellola/ mm3 kien osservat fi 13% u fi 11% tal- pazjenti li rċevew Pegasys waħdu jew f’ terapija kombinata, rispettivament.
Decrease in platelets below 50,000/ mm3 was observed in 10% and 8% of patients receiving Pegasys monotherapy and combination therapy, respectively.
Tnaqqis fil- plejtlits taħt 50, 000/ mm3 kien osservat f’ 10% u fi 8% tal- pazjenti li rċevew Pegasys waħdu jew f’ terapija kombinata, rispettivament.
Anaemia (haemoglobin < 10g/ dL) was reported in 7% and 14% of patients treated with Pegasys monotherapy or in combination therapy, respectively.
Anemija (emoglobina < 10g/ dL) kienet irrapportata f’ 7% u f’ 14% tal- pazjenti li rċevew Pegasys waħdu jew f’ terapija kombinata, rispettivament.
Overdoses involving between two injections on consecutive days (instead of weekly interval) up to daily injections for1 week (ie, 1260 micrograms/ week) have been reported.
Dożi eċċessivi li jvarjaw minn żewġ injezzjonijiet fi ġranet konsekuttivi (minflok interval ta ’ ġimgħa) sa injezzjonijiet ta ’ darba kuljum għal ġimgħa waħda (jiġifieri, 1260 mikrogramma/ ġimgħa) kienu rapportati.
None of these patients experienced unusual, serious or treatment-limiting events.
L- ebda minn dawn il- pazjenti ma kellhom sintomi mhux tas- soltu, serji jew li tellfu l- kura.
Weekly doses of up to 540 and 630 micrograms have been administered in renal cell carcinoma and chronic myelogenous leukaemia clinical trials, respectively.
Dożi sa 540 u 630 mikrogramma fil- ġimgħa kienu mogħtija fi provi kliniċi f’ każijiet ta ’ karċinoma taċ - ċelloli renali u b’ lewkimja majeloġenika kronika, rispettivament.
Dose limiting toxicities were fatigue, elevated liver enzymes, neutropenia and thrombocytopenia, consistent with interferon therapy.
Tossiċitajiet li llimitaw id- doża kienu għejja, livelli għoljin ta ’ enżimi tal- fwied, newtropenja u tromboċitopenja, konsistenti ma ’ terapija b’ interferon.
Immunostimulating Agent/ Cytokine, ATC code:
Aġent immunostimulatorju/ Ċitokina, Kodiċi ATC:
The conjugation of PEG reagent (bis-monomethoxypolyethylene glycol) to interferon alfa-2a forms a pegylated interferon alfa-2a (Pegasys).
Il- konjugazzjoni tar- reaġent PEG (bis - [monomethoxy polyethylene glycol] ma ’ interferon alfa- 2a jifforma pegylated interferon alfa- 2a (Pegasys).
Pegasys possesses the in vitro antiviral and antiproliferative activities that are characteristic of interferon alfa-2a.
Pegasys in vitro għandu l- attivitajiet antivirali u antiproliferattivi li huma karatteristiċi ta ’ interferon alfa- 2a.
16 Interferon alfa-2a is conjugated with bis-[monomethoxy polyethylene glycol] at a degree of substitution of one mole of polymer/ mole of protein. The average molecular mass is approximately 60,000 of which the protein moiety constitutes approximately 20,000.
Il- piż molekulari medju huwa ta ’ madwar 60, 000 li minnu l- parti tal- proteina tikkostitwixxi madwar 20, 000.
HCV RNA levels decline in a biphasic manner in responding patients with hepatitis C who have received treatment with 180 micrograms Pegasys.
Il- livelli ta ’ HCV RNA jonqsu b’ mod bi- fażiku f’ pazjenti b’ epatite Ċ li kellhom rispons għal- kura b’ 180 mikrogrammi Pegasys.
The first phase of decline occurs 24 to 36 hours after the first dose of Pegasys and is followed by the second phase of decline which continues over the next 4 to 16 weeks in patients who achieve a sustained response.
L- ewwel fażi tat- tnaqqis isseħħ bejn 24 sa 36 siegħa wara l- ewwel doża ta ’ Pegasys u hija segwita mit- tieni fażi ta ’ tnaqqis li tkompli fir- raba ’ sa 16- il ġimgħa f’ pazjenti li jilħqu rispons sostenut.
Ribavirin had no significant effect on the initial viral kinetics over the first 4 to 6 weeks in patients treated with the combination of ribavirin and pegylated interferon alfa-2a or interferon alfa.
Ribavirin ma kellu l- ebda effett sinifikanti fuq il- kinetiċi virali tal- bidu fl- ewwel 4 sa 6 ġimgħat f’ pazjenti li kienu kkurati bit- taħlita ta ’ ribavirin u pegylated interferon alfa- 2a jew interferon alfa.
Study WV16240 recruited patients who were positive for HBeAg, while study WV16241 recruited patients who were negative for HBeAg and positive for anti-HBe.
Riżultati tal- provi kliniċi Il- provi kliniċi kollha rreklutaw pazjenti b’ epatite B kronika li kellhom replikazzjoni virali attiva mkejjla b’ HBV DNA, livelli għolja ta ’ ALT u bijopsija tal- fwied konsistenti ma ’ epatite kronika. l - Studju WV16240 irrekluta pazjenti li kienu pożittivi għal HBeAg, waqt li studju WV16241irrekluta pazjenti li kienu negattivi għal HBeAg u pożittivi għal anti- HBe.
In both studies the treatment duration was 48 weeks, with 24 weeks of treatment-free follow-up.
Fiż- żewġ studji t- tul ta ’ kura kien ta ’ 48 ġimgħa, b’ 24 ġimgħa ta ’ wara bla kura.
Both studies compared Pegasys plus placebo vs Pegasys plus lamivudine vs lamivudine alone.
Iż- żewġ studji qabblu Pegasys u plaċebo vs Pegasys u lamivudine vs lamivudine waħdu.
No HBV-HIV co-infected patients were included in these clinical trials.
Pazjenti ko- infettat b’ HBV- HIV ma kienux inklużi f’ dawn il- provi kliniċi.
Response rates at the end of follow-up for the two studies are presented in Table 5.
Ir- rati ta ’ rispons fl- aħħar tal- perijodu ta ’ wara għaż- żewġ studji huma ppreżentati f’ Tabella 5.
In study WV16240, the primary efficacy endpoints were HBeAg seroconversion and HBV-DNA below 105 copies/ ml.
Fl - istudju WV16240, l- miri primarji tal- effikaċja kienu s- serokonverżjoni ta ’ HBeAg u HBV DNA taħt 105 kopja/ ml.
In study WV16241, the primary efficacy endpoints were ALT normalisation and HBV-DNA below 2 x 104 copies/ ml.
Fl- istudju WV16241, il- miri primarji tal- effikaċja kienu normalizzazzjoni ta ’ ALT u HBV
HBV-DNA was measured by the COBAS AMPLICOR™ HBV MONITOR Assay (limit of detection 200 copies/ ml).
HBV DNA kienet imkejjla b’ Analiżi COBAS AMPLICOR™ HBV MONITOR (limitu ta ’ kemm jista ’ jiġi mkejjel ta ’ 200 kopja/ ml).
A total of 283/ 1351 (21%) of patients had advanced fibrosis or cirrhosis, 85/ 1351 (6%) had cirrhosis.
Total ta ’ 283/ 1351 (21%) tal- pazjenti kellhom fibrożi avvanzata jew ċirrożi, 85/ 1351 (6%) kellhom ċirrożi.
There was no difference in response rate between these patients and those without advanced fibrosis or cirrhosis.
Ma kienx hemm differenza fir- rata ta ’ rispons bejn dawn il- pazjenti u dawk mingħajr fibrożi avvanzata jew ċirrożi.
Serological, Virological and Biochemical Responses in Chronic Hepatitis B
Risponsi Seroloġiċi, Viroloġiċi u Bijokimiċi f’ Epatite B Kronika
HBeAg positive Study WV16240
Pożittivi għal HBeAg Studju WV16240
HBeAg negative / anti-HBe positive Study WV16241
għal HBeAg / pożittivi għal anti- HBe Studju WV16241
Response Parameter
Parametru ta ’ Rispons
(N=272)
& Plaċebo
(N=177)
& Lamivudine 100 mg
(N=179)
& Plaċebo
(N=181)
& Lamivudine 100 mg
HBeAg Sero- conversion
Serokonverżj oni ta ’ HBeAg
32% #
(N=271) 32% #
27%
(N=271) 27%
19%
(N=272) 19%
N/ A
(N=177) N/ A
N/ A
(N=179) N/ A
N/ A
(N=181) N/ A
HBsAg Sero- conversion
Serokonverżj oni ta ’ HBsAg
* For HBeAg-positive patients:
* Għall- pazjenti pożittivi għal HBeAg:
HBV DNA < 105 copies/ ml For HBeAg-negative / anti-HBe-positive patients:
HBV DNA < 105 kopji/ ml Għall- pazjenti negattivi għal HBeAg/ pożittivi għal anti- HBe:
HBV DNA < 2 x 104 copies/ ml
HBV DNA < 2 x 104 kopji/ ml
# p-value (vs. lamivudine) < 0.01 (stratified Cochran-Mantel-Haenszel test)
# valur ta ’ p (vs. lamivudine) < 0. 01 (test Cochran- Mantel- Haenszel stratifikat)
17 Histological response was similar across the three treatment groups in each study; however, patients showing a sustained response 24 weeks after the end of treatment were significantly more likely to also show histological improvement.
Ir- rispons istoloġiku kien simili tul it- tlett gruppi ta ’ kura f’ kull studju; madanakollu, pazjenti li wrew rispons sostenut 24 ġimgħa wara t- tmiem tal- kura kienu sinifikatament aktar probabbli li juru wkoll titjib istoloġiku.
All patients who completed the phase III studies were eligible for entry into a long-term follow-up study (WV16866).
Il- pazjenti kollha li temmew l- istudji ta ’ fażi III setgħu jidħlu fl- istudju fit- tul ta ’ wara (WV16866).
Among patients from study WV16240, who received Pegasys monotherapy and entered the long-term follow-up study, the rate of sustained HBeAg seroconversion 12 months after the end of therapy was 48% (73/ 153).
Fost il- pazjenti mill- istudju WV16240, li rċevew monoterapija ta ’ Pegasys u li daħlu fl- istudju fit- tul ta ’ wara, ir- rata ta ’ serokonverżjoni sostenuta ta ’ HBeAg, 12- il xahar wara t- tmiem tat- terapija kienet 48% (73/ 153).
In patients receiving Pegasys monotherapy in study WV16241, the rate of HBV DNA response and ALT normalisation 12 months after end of treatment were 42% (41/ 97) and 59% (58/ 99), respectively.
F’ pazjenti li rċevew monoterapija ta ’ Pegasys fl- istudju WV16241, ir- rata ta ’ rispons tad - HBV DNA u n- normalizzazzjoni ta ’ ALT 12- il xahar wara t- tmiem tat- terapija kienu 42% (41/ 97) u 59% (58/ 99), rispettivament.
Predictability of response Please refer to section 4.2, in Table 2.
Tbassir tar- rispons Jekk jogħġbok ara sezzjoni 4. 2, f’ Tabella 2.
Dose-response in monotherapy In a direct comparison with 90 micrograms, the 180 micrograms-dose was associated with superior sustained virological response in patients with cirrhosis, but in a study in non-cirrhotic patients very similar results were obtained with doses of 135 micrograms and 180 micrograms.
Rispons skond id- doża fil- monoterapija Meta imqabbel direttament ma ’ 90 mikrogramma, id- doża ta ’ 180 mikrogramma kienet assoċjata ma ’ effett viroloġiku akbar u sostenut f’ pazjenti b’ ċirrożi, iżda fi studju b’ pazjenti mhux ċirrotiċi b’ dożi ta ’ 135 mikrogramma u 180 mikrogramma r- riżultati kienu simili ħafna.
Confirmatory clinical trials in treatment-naïve patients All clinical trials recruited interferon-naïve patients with chronic hepatitis C confirmed by detectable levels of serum HCV RNA, elevated levels of ALT (with the exception of study NR16071) and a liver biopsy consistent with chronic hepatitis.
Provi kliniċi konfermatorji f’ pazjenti li qatt ma jkunu ħadu kura qabel Waqt il- provi kliniċi kollha, il- pazjenti kollha li ħadu sehem ma kienux jafu li qed jieħdu interferon u kienu konfermati li jsofru minn epatite Ċ kronika mill- livelli mkejla fis- serum ta ’ HCV RNA, livelli elevati ta ’ ALT (bl- eċċezzjoni ta ’ studju NR16071) u minn bijopsija tal- fwied konsistenti ma ’ epatite
Study NV15495 specifically recruited patients with a histological diagnosis of cirrhosis (about 80%) or transition to cirrhosis (about 20%).
Fl- istudju NV15495 ħadu sehem speċifikament pazjenti b’ dijanjożi istoloġika ta ’ ċirrożi (bejn wieħed u ieħor 80%) jew transizzjoni għal ċirrożi (bejn wieħed u ieħor 20%).
Only HIV-HCV co-infected patients were included in the study NR15961 (see Table 14).
Pazjenti ko- infettat b’ HCV/ HIV biss kienu inklużi fl - istudju NR15961 (ara Tabella 14).
For HCV monoinfected patients and HIV-HCV co-infected patients, for treatment regimens, duration of therapy and study outcome see Tables 6, 7, 8 and Table 14, respectively.
Dawn il- pazjenti kellhom marda tal- HIV stabbli u l- għadd medju taċ- ċelloli T CD4 kien ta ’ madwar 500 ċellola/ µL. rispons F’ pazjenti infettati biss b’ HCV u pazjenti ko- infettati b’ HIV- HCV, għad- dożaggi ta ’ kura, tul tat - terapija u riżultati ta ’ l- istudju ara Tabelli 6, 7, 8 u 14, rispettivament.
Virological response was defined as undetectable HCV RNA as measured by the COBAS AMPLICOR™ HCV Test, version 2.0 (limit of detection 100 copies/ ml equivalent to 50 International Units/ ml) and sustained response as one negative sample approximately 6 months after end of therapy.
Rispons viroloġiku kien definit bħala livell ta ’ HCV RNA li ma jistax jitkejjel, kif imkejjel bit- test COBAS AMPLICOR™ HCV, verżjoni 2. 0 (limitu tal- kejl 100 kopja/ ml ekwivalenti għal 50 Unitajiet Internazzjonali/ ml) u r- rispons sostenut li deher bħala kampjun negattiv wieħed madwar 6 xhur wara t- tmiem tat- terapija.
Virological Response in HCV Patients
Rispons Viroloġiku f’ Pazjenti b’ HCV
Pegasys Monotherapy
Monoterapija b' Pegasys
Pegasys Combination Therapy
Terapija kombinata b' Pegasys
cirrhotic and cirrhotic cirrhotic
Mhux ċirrotiċi u ċirrotiċi
non-cirrhotic and cirrhotic
Mhux ċirrotiċi u ċirrotiċi
Study NV15496 +
Studju NV15496 +
Study NV15495 Study
Studju NV15495 Stud
Study NV15496 + Study NV15495 Study
Studju NV15496 + Studju NV15495 Studju
Study NV15801
Studju NV15801
6 MIU/
6 MIU/ 3 MIU
3 MIU 3 MIU & & &
3 MIU
3 MIU &
MIU
Ribavirin Ribavirin 1000/ 1200 1000/ 1200 mg mg
1000/ 1200 1000/ 1200 1000/ 1200
Ribavirin 1000/ 1200 mg
mg
(N=88)
(N=436)
48 weeks 48
48 ġimgħa 48 ġimgħa
weeks 48 weeks 48
48 ġimgħa 48 ġimgħa
weeks 48 weeks
48 ġimgħa
at End of Treatment
ġimgħa Rispons fl - aħħar tal - kura
55 - 69%
55- 69%
22 - 28%
22- 28%
Sustained Response
Rispons sostenut ġenerali
28 - 39%
28- 39%
11 - 19%
11- 19%
45%**
45 **
* 95% CI for difference:
* 95% CI għad- differenza:
11% to 33% ** 95% CI for difference:
11% sa 33% ** 95% CI għad- differenza:
3% to 16%
3% sa 16%
p-value (stratified Cochran-Mantel-Haenszel test) = 0.001 p-value (stratified Cochran-Mantel-Haenszel test)=0.003
valur- p (test Cochran- Mantel- Haenzel stratifikat) = 0. 001 valur- p (test Cochran- Mantel- Haenzel stratifikat) = 0. 003
The virological responses of HCV monoinfected patients treated with Pegasys monotherapy and with Pegasys and ribavirin combination therapy in relation to genotype and pre-treatment viral load and in relation to genotype, pre-treatment viral load and rapid virological response at week 4 are summarised in Table 7 and Table 8, respectively.
Ir- rispons viroloġiku ta ’ pazjenti infettati biss b’ HCV kkurati bil- monoterapija ta ’ Pegasys u bit- terapija kombinata ta ’ Pegasys u ribavirin b’ relazzjoni mal- ġenotip u l- viral load ta ’ qabel il- kura u b’ relazzjoni mal- ġenotip, l- viral load ta ’ qabel il- kura u r- rispons viroloġiku rapidu fir- raba ’ ġimgħa huma miġbura f’ Tabella 7 u f’ Tabella 8 rispettivament.
The results of study NV15942 provide the rationale for recommending treatment regimens based on genotype, baseline viral load and virological response at week 4 (see Tables 1, 7 and 8).
Ir- riżultati ta ’ l- istudju NV15942 jipprovdu r- raġunijiet wara l - għażla tat- tipi ta ’ kura rakkomandati skond il- ġenotip, viral load fil- linja bażi u r- rispons viroloġiku fir - raba ’ ġimgħa (ara Tabelli 1, 7 u 8).
The difference between treatment regimens was in general not influenced by presence/ absence of cirrhosis; therefore treatment recommendations for genotype 1, 2 or 3 are independent of this baseline characteristic.
Id- differenza bejn it- tipi ta ’ kura ġeneralment ma kienetx influwenzata mill- preżenza/ assenza ta ’ ċirrożi; għalhekk il- kura rakkomandata għall- ġenotip 1, 2 jew 3 hija indipendenti minn din il- karatteristika tal - linja bażi.
19 Table 7:
19 Tabella 7:
Sustained Virological Response Based on Genotype and Pre-treatment Viral Load after Pegasys Combination Therapy with Ribavirin in HCV Patients
Rispons Viroloġiku Sostenut ibbażat fuq il- Ġenotip u l- Viral load ta ’ Qabel il- Kura wara Terapija Kombinata ta ’ Pegasys ma ’ Ribavirin f’ Pazjenti b’ HCV
Study NV15942
Studju NV15942
Study NV15801
Studju NV15801 Interferon
Pegasys Pegasys Pegasys Pegasys Pegasys 180 mcg 180 mcg 180 mcg 180 mcg 180 mcg
180
Interferon alfa-2b 3 MIU
mcg 180 mcg 180 mcg 180 mcg
& & & & &
3 MIU u
&
u
Ribavirin Ribavirin Ribavirin Ribavirin Ribavirin
Ribavirin Ribavirin Ribavirin Ribavirin
1000/ 1200 mg 800 mg 1000/ 1200 mg 1000/ 1200 mg
1000/ 1200 mg 800 mg
24 weeks 24 weeks
48 ġimgħa
48 weeks 48 weeks 48 weeks
48 ġimgħa
Genotype 1 Low viral load High viral load
Ġenotip 1 Viral load
Genotype 2/ 3 Low viral load High viral load Genotype 4
Ġenotip 2/ 3 Viral load
Low viral load= ≤ 800,000 IU/ mL; High viral load= > 800,000 IU/ mL * Pegasys 180 mcg ribavirin 1000/ 1200 mg, 48 w vs.
Viral load baxxa= ≤ 800, 000 IU/ mL; Viral load għolja= > 800, 000 IU/ mL * Pegasys 180 mcg ribavirin 1000/ 1200 mg, 48 ġ vs.
Pegasys 180 mcg ribavirin 800 mg, 48 w:
Pegasys 180 mcg ribavirin 800 mg, 48 ġ:
Odds Ratio (95% CI) = 1.52 (1.07 to 2.17) P-value (stratified Cochran-Mantel-Haenszel test) = 0.020 * Pegasys 180 mcg ribavirin 1000/ 1200 mg, 48 w vs.
Odds Ratio (95% CI) = 1. 52 (1. 07 sa 2. 17) Valur- p (test Cochran- Mantel- Haenzel stratifikat) = 0. 020 * Pegasys 180 mcg ribavirin 1000/ 1200 mg, 48 ġ vs.
Pegasys 180 mcg ribavirin 1000/ 1200 mg, 24 w:
Pegasys 180 mcg ribavirin 1000/ 1200 mg, 24 ġ:
Odds Ratio (95% CI) = 2.12 (1.30 to 3.46)
Odds Ratio (95% CI) = 2. 12 (1. 30 sa 3. 46)
P-value (stratified Cochran-Mantel-Haenszel test) = 0.002.
Valur- p (test Cochran- Mantel- Haenzel stratifikat) = 0. 002
The possibility to consider shortening treatment duration to 24 weeks in genotype 1 and 4 patients was examined based on a sustained rapid virological response observed in patients with rapid virological response at week 4 in studies NV15942 and ML17131 (see Table 8).
Il- possibilità li jiġi kkunsidrat tnaqqis fit- tul tal- kura għal 24 ġimgħa f’ pazjenti b’ ġenotip 1 u 4 kienet studjata bbażata fuq rispons viroloġiku rapidu sostenut osservat f’ pazjenti b’ rispons viroloġiku rapidu mar- raba ’ ġimgħa fl- istudji NV15942 u ML17131 (ara Tabella 8).
Sustained Virological Response Based on Rapid Viral Response at week 4 for Genotype 1 and 4 after Pegasys Combination Therapy with Ribavirin in HCV Patients
Rispons Viroloġiku Sostenut Ibbażat fuq Rispons Virali Rapidu mar- raba ’ Gimgħa f’ Pazjenti b’ HCV ta ’ Genotip 1 u 4 wara Kura Kombinata ta ’ Pegasys ma ’ Ribavirin
Study ML17131
Studju ML17131
1000/ 1200 mg 24 weeks
Ġenotip 1 RVR
1000/ 1200 mg 48 weeks
1000/ 1200 mg 1000/ 1200 mg 24 ġimgħa 48 ġimgħa 90% (28/ 31) 92% (47/ 51)
1000/ 1200 mg 24 weeks
1000/ 1200 mg 24 ġimgħa 77% (59/ 77)
Genotype 1 RVR Low viral load High viral load Genotype 1 non RVR Low viral load High viral load
Viral load għolja Ġenotip 1 mhux
90% (28/ 31) 93% (25/ 27) 75% (3/ 4) 24% (21/ 87) 27% (12/ 44) 21% (9/ 43)
75% (3/ 4) 88% (21/ 24)
92% (47/ 51) 96% (26/ 27) 88% (21/ 24) 43% (95/ 220) 50% (31/ 62) 41% (64/ 158)
24% (21/ 87) 43% (95/ 220)
77% (59/ 77) 80% (52/ 65) 58% (7/ 12) - - -
27% (12/ 44) 50% (31/ 62)
Genotype 4 RVR
Viral load għolja
(5/ 6)
Ġenotip 4 RVR
Genotype 4 non RVR
Ġenotip 4 mhux RVR
Low viral load= ≤ 800,000 IU/ mL; High viral load= > 800,000 IU/ mL RVR = rapid viral response (HCV RNA undetectable) at week 4 and HCV RNA undetectable at week 24
Viral load baxxa= ≤ 800, 000 IU/ mL; Viral load għolja= > 800, 000 IU/ mL RVR = rispons virali rapidu (HCV RNA mhux osservat) fir- raba ’ ġimgħa u HCV RNA mhux osservat f’ ġimgħa 24
20 Although limited, data indicated that shortening treatment to 24 weeks might be associated with a higher risk of relapse (see Table 9).
20 Għalkemm limitat, it- tagħrif jindika li tqassir tal- kura għal 24 ġimgħa jista ’ jkun assoċjat ma ’ riskju akbar li wieħed jirkadi (ara Tabella 9).
Relapse of Virological Response at the End of Treatment for Rapid Virological Response Population
Rikaduta tar- Rispons Viroloġiku fit- Tmiem tal- Kura għall- Popolazzjoni ta ’ Rispons Viroloġiku Rapidu
1000/ 1200 mg 1000/ 1200 mg 24 weeks 48 weeks
1000/ 1200 mg 1000/ 1200 mg 24 ġimgħa 48 ġimgħa 6. 7% (2/ 30) 4. 3% (2/ 47)
1000/ 1200 mg 48 weeks
1000/ 1200 mg 48 ġimgħa 0% (0/ 24)
Genotype 1 RVR
Viral load baxxa
6.7% (2/ 30) 4.3% (2/ 47)
3. 8% (1/ 26) 0% (0/ 25)
0% (0/ 24)
0% (0/ 17)
Low viral load High viral load Genotype 4 RVR
Viral load għolja
3.8% (1/ 26) 0% (0/ 25) 25% (1/ 4) 9.1% (2/ 22) (0/ 5) (0/ 5)
25% (1/ 4) 9. 1% (2/ 22)
0% (0/ 17) 0% (0/ 7) 0% (0/ 4)
0% (0/ 7)
The possibility of shortening treatment duration to 16 weeks in genotype 2 or 3 patients was examined based on a sustained virological response observed in patients with rapid virological response by week 4 in study NV17317 (see Table 10).
Il- possibbiltà li t- tul tal- kura jiġi mqassar għal 16- il ġimgħa f’ pazjenti b’ ġenotip 2 jew 3 kienet eżaminata fuq il- bażi tar- rispons viroloġiku sostenut osservat f’ pazjenti b’ rispons viroloġiku mgħaġġel mar- raba ’ ġimgħa fi studju NV17317 (ara Tabella 10).
In study NV17317 in patients infected with viral genotype 2 or 3, all patients received Pegasys 180 μ g sc qw and a ribavirin dose of 800 mg and were randomized to treatment for either 16 or 24 weeks.
Fi studju NV17317 f’ pazjenti infetti b’ ġenotip virali 2 jew 3, il- pazjenti kollha rċevew Pegasys 180 μg sc qw u doża ta ’ ribavirin ta ’ 800 mg u kienu randomised għall- kura ta ’ 16 jew 24 ġimgħa.
Overall treatment for 16 weeks resulted in lower sustained viral response (65%) than treatment for 24 weeks (76%) (p < 0.0001).
Kura totali għal 16- il ġimgħa wasslet għal rispons virali sostenut aktar baxx (65%) minn kura għal 24 ġimgħa (76%) (p < 0. 0001).
The sustained viral response achieved with 16 weeks of treatment and with 24 weeks of treatment was also examined in a retrospective subgroup analysis of patients who were HCV RNA negative by week 4 and had a LVL at baseline (see Table 10).
Ir- rispons virali sostenut miksub b’ 16- il ġimgħa ta ’ kura u b’ 24 ġimgħa ta ’ kura kien eżaminat ukoll f’ analiżi retrospettiv ta ’ sottogrupp ta ’ pazjenti li kienu negattivi għal HCV RNA mar- raba ’ ġimgħa u li kellhom LVL fil- linja bażi (ara Tabella 10).
Table 10:
Tabella 10.
Sustained Virological Response Overall and Based on Rapid Viral Response by Week 4 for Genotype 2 or 3 after Pegasys Combination Therapy with Ribavirin in HCV Patients Study NV17317
Rispons Viroloġiku Sostenut Totali u Bbażat fuq Rispons Virali Rapidu mar- Raba ’ Ġimgħa għall- Ġenotip 2 jew 3 wara Terapija Kombinata ta ’ Pegasys b’ Ribavirin f’ Pazjenti b’ HCV
Treatment difference 95%CI
180 mcg
Ribavirin 800 mg 16 weeks
180 mcg &
Ribavirin 800 mg 24 weeks
&
-10.6%
- 0. 06%]
[-15.5%; - P < 0.0001 0.06%]
P < 0. 0001
Genotype 2 or 3 RVR
- 8. 2% [- 12. 8%; - 3. 7%] Ġenotip 2 jew 3 RVR
High viral load
Viral load baxxa
-9.7% [-15.9%; -
- 9. 7% [- 15. 9%; - 3. 6%] Viral load għolja
Low viral load= ≤ 800,000 IU/ mL; High viral load= > 800,000 IU/ mL RVR = rapid viral response (HCV RNA undetectable) at week 4
Viral load baxxa = ≤ 800, 000 IU/ mL; Viral load għolja = > 800, 000 IU/ mL RVR = rispons virali rapidu (HCV RNA mhux osservat) fir- raba ’ ġimgħa
21 The data indicated that shortening treatment to 16 weeks is associated with a higher risk of relapse (see Table 11).
It- tagħrif indika li tqassir tal- kura għal 16- il ġimgħa huwa assoċjat ma ’ riskju ogħla ta ’ rkadar (ara Tabella 11).
Table 11:
21 Tabella 11:
Relapse of Virological Response after the End of Treatment in Genotype 2 or 3 Patients with a Rapid Viral Response Study NV17317
Rkadar tar- Rispons Viroloġiku wara t- Tmiem tal- Kura f’ pazjenti b’ Ġenotip 2 jew 3 b’ Rispons Virali Rapidu
Pegasys Pegasys
Studju NV17317
difference 95%CI
Ribavirin 800 mg 24 ġimgħa
Ribavirin 800 mg 16 weeks
Viral load baxxa = ≤ 800, 000 IU/ mL; Viral load għolja = > 800, 000 IU/ mL RVR = rispons virali rapidu (HCV RNA mhux osservat) fir- raba ’ ġimgħa
Ribavirin 800 mg 24 weeks
Pazjenti b’ epatite Ċ kronika li ma rrispondewx għall- kura ta ’ qabel
Genotype 2 or 3
Il- gruppi ta ’ kura kollha kellhom perijodu ta ’ wara ta ’ 24 ġimgħa bla kura.
15%
Differenzi fir- rispons viroloġiku sostenut (SVR) ibbażati fuq it- tul tal- kura, demografiċi u l- aħjar risponsi għall- kura ta ’ qabel huma mniżżla f’ Tabella 12.
6% (23/ 386)
22 Tabella 12:
9.3% [5.2%;
Pegasys 360/ 180 jew 180 μg & Ribavirin 1000/ 1200 mg 72 jew 48 Ġimgħa (N = 942) Pażjenti b ’ VR f’ Ġimgħa 12 a (N = 876) 18% (157/ 876)
P < 0.0001
Pegasys 360/ 180 jew 180 μg & Ribavirin 1000/ 1200 mg 72 Ġimgħa (N = 473) SVR f’ Pażjenti b ’ VR f’ Ġimgħa 12 b (N = 100) 57% (57/ 100)
RVR
Pegasys 360/ 180 jew 180 μg & Ribavirin 1000/ 1200 mg 48 Ġimgħa (N = 469) SVR f’ Pażjenti b ’ VR f’ Ġimgħa 12 b (N = 57) 35% (20/ 57)
(67/ 439)
Viral load baxxa Viral load għolja Ġenotip 1/ 4
1% (2/ 141)
35% (56/ 159) 14% (97/ 686) 17% (140/ 846)
13.6%]
63% (22/ 35) 54% (34/ 63) 55% (52/ 94)
P=0.04
38% (8/ 21) 32% (11/ 34) 35% (16/ 46)
Low viral load
Viral load baxxa Viral load għolja
9% (21/ 245)
35% (54/ 154) 13% (84/ 663)
5% [0.6%;
63% (22/ 35) 52% (30/ 58)
High viral load
37% (7/ 19) 35% (9/ 26) (3/ 10)
(10/ 155)
Ġenotip 2/ 3
10.3%]
58% (15/ 26)
20%
(4/ 5)
11.5% [5.6%;
Viral load baxxa
17.4%]
—
Low viral load= ≤ 800,000 IU/ mL; High viral load= > 800,000 IU/ mL RVR = rapid viral response (HCV RNA undetectable) at week 4
(1/ 2) (1/ 7)
All treatment arms had 24 week treatment-free follow-up.
Viral load għolja Stat ta ’ Ċirrosi
22 Table 12:
(11/ 19) 8% (19/ 239)
Pegasys 360/ 180 or Pegasys 360/ 180 or 180 μ g 180 μ g & & Ribavirin 1000/ 1200 Ribavirin mg 1000/ 1200 mg 72 or 48 Weeks 72 Weeks (N = 942) (N = 473) Pts with SVR in Pts with VR at Wk 12 a VR at Wk 12 b (N = 876) (N = 100)
(3/ 4)
Pegasys 360/ 180 or 180 μ g & Ribavirin 1000/ 1200 mg 48 Weeks (N = 469) SVR in Pts with VR at Wk 12 b (N = 57)
Ċirrosi
Overall Low viral load High viral load Genotype 1/ 4 Low viral load High viral load Genotype 2/ 3 Low viral load High viral load Cirrhosis Status
22% (137/ 633)
Cirrhosis Noncirrhosis Best Response during Previous Treatment
Bla ċirrosi L- Aħjar Rispons waqt Kura ta ’ Qabel
≥ 2log10 decline in HCV RNA < 2log10 decline in HCV RNA Missing best previous response
Tnaqqis ta ’ ≥2log10 f’ HCV RNA
High viral load = > 800,000 IU/ mL, low viral load = ≤ 800,000 IU/ mL. a Patients who achieved viral suppression (undetectable HCV RNA, < 50 IU/ mL) at week 12 were considered to have a virological response at week 12.
Viral load għolja= > 800, 000 IU/ mL, viral load baxxa = ≤ 800, 000 IU/ mL. a Pazjenti li laħqu soppressjoni virali (HCV RNA li ma jistax jiġi osservat, < 50 IU/ mL) fit- 12- il ġimgħa kienu kkunsidrati li għandhom rispons viroloġiku fit- 12- il ġimgħa.
Patients missing HCV RNA results at week 12 have been excluded from the analysis. b Patients who achieved viral suppression at week 12 but were missing HCV RNA results at the end of follow-up were considered to be nonresponders
Pazjenti nieqsa minn riżultati ta ’ HCV RNA fit- 12- il ġimgħa kienu esklużi mill - analiżi. b Pazjenti li laħqu soppressjoni virali fit- 12- il ġimgħa iżda li kellhom r- riżultati ta ’ HCV RNA nieqsa fl- aħħar tal- vista ta ’ wara kienu kkunsidrati bħala li ma rrispondewx
In the HALT-C study, patients with chronic hepatitis C and advanced fibrosis or cirrhosis who were non-responders to previous treatment with interferon alfa or pegylated interferon alfa monotherapy or in combination therapy with ribavirin were treated with Pegasys 180 mcg/ week and ribavirin 1000/ 1200 mg daily.
Fl- istudju HALT- C, pazjenti b’ epatite Ċ kronika u b’ fibrożi jew ċirrożi avvanzata li ma rrispondewx għall kura ta ’ qabel b’ monoterapija ta ’ interferon alfa jew pegylated interferon alfa jew terapija kombinata ma ’ ribavirin kienu kkurati b’ Pegasys 180 mcg/ ġimgħa u ribavirin 1000/ 1200 mg kuljum.
The probability for sustained virological response varied depending upon the previous treatment regimen; see Table 13.
Pazjenti li laħqu livelli ta ’ HCV RNA li ma kienux osservati wara 20 ġimgħa ta ’ kura baqgħu fuq terapija kombinata ta ’ Pegasys flimkien ma ’ ribavirin għal total ta ’ 48 ġimgħa u wara kienu segwiti għal 24 ġimgħa wara t- tmiem tal- kura.
Table 13 Sustained Virological Response in HALT-C by Previous Treatment Regimen in Non-responder Population Previous Treatment
Il- probabbiltà ta ’ rispons viroloġiku sostenut varjat skond il- kors tal - kura ta ’ qabel; ara Tabella 13.