qanastek/EMEA-V3 huggingface dataset:
Patients who “ failed to respond to ” in the target population is defined by insufficient response (PASI < 50 or PGA less than good), or worsening of the disease while on treatment, and who were adequately dosed for a sufficiently long duration to assess response with at least each of the three major systemic therapies as available.
Pazjenti li “ fallew milli jirrispondu ” mill- popolazzjoni mmirata huma mfissra b’ risponsi insuffiċjenti (PASI < 50 jew PGA anqas minn tajba) jew deterjorament tal- marda waqt l- għoti tal- kura, u li kienu dożati adegwatament għal tul ta ’ żmien suffiċjenti biex jiġi assessjat ir- rispons b ’ ta ’ lanqas kull waħda mit- tliet terapiji sistemiċi kif jeżistu.
The primary efficacy endpoint in all four studies was the proportion of patients in each treatment group who achieved the PASI 75 (i. e. at least a 75% improvement in the Psoriasis Area and Severity Index score from baseline) at 12 weeks.
L- endpoint ta ’ l- effikaċja primarja fl- erba ’ studji kollha kien il- proporzjon ta ’ pazjenti f’ kull grupp ta ’ trattament li kisbu PASI 75 (i. e., mill - anqas 75% titjib B’ PUNTEĠĠ tal- Psoriasis Area and Severity Index mil- linja bażi) fit- 12- il ġimgħa.
49 Study 1 was a Phase 2 study in patients with active but clinically stable plaque psoriasis involving  10% of the body surface area that were  18 years old.
Studju 1 kien prova ta ’ Fażi 2 f’ pazjenti bi psorjasi tal- plakka klinikament stabbli imma attiva li tinvolvi ≥ 10% tal- erja tal- wiċċ tal- ġisem li kellhom ≥ 18- il sena.
Study 2 evaluated 652 patients with chronic plaque psoriasis using the same inclusion criteria as study 1 with the addition of a minimum psoriasis area and severity index (PASI) of 10 at screening.
Studju 2 evalwa 652 pazjent bi psorasi tal- plakka kronika billi ntużaw l- istess kriterji ta ’ inklużjoni bħal fi studju 1 biż- żieda ta ’ minimum psoriasis area and severity index (PASI) ta ’ 10 waqt screening.
After 12 weeks of treatment, patients in the placebo group began treatment with blinded Enbrel (25 mg twice a week); patients in the active treatment groups continued to week 24 on the dose to which they were originally randomised.
Wara tnax- il ġimgħa ta ’ trattament, pazjenti fil- grupp plaċebo bdew trattament blinded b’ Enbrel (25 mg darbtejn fil - ġimgħa); pazjenti fil- grupp tat- trattament attiv komplew sa ġimgħa 24 fuq id- doża li fiha kienu magħżula b’ mod każwali fil- bidu nett.
RESPONSES OF PATIENTS WITH PSORIASIS IN STUDIES 2, 3 AND 4 ------------------Study 2--------------- ---------------Study 3------------- ---------------Study 4-------------
48 REAZZJONIJIET TA ’ PAZJENTI BI PSORJASI FI STUDJI 2, 3 U 4 -------------------- Studju 2 ------------------ ---------------- Studju 3 ------------- ------------- Studju 4 ------------
Clear or almost clear defined as 0 or 1 on a 0 to 5 scale.
Dermatologist Static Global Assessment. Ikkurati jew kważi ikkurati iddefiniti bħala 0 jew 1 fuq skala 0 to 5.
Among patients with plaque psoriasis who received Enbrel, significant responses relative to placebo were apparent at the time of the first visit (2 weeks) and were maintained through 24 weeks of therapy.
Fost pazjenti b’ psorjasi tal- plakka li ngħataw Enbrel, risponsi sinifikattivi relattivi ma ’ plaċebo kienu jidhru waqt iż- żmien ta ’ l- ewwel viżta (2 ġimgħat) u kienu miżmumin waqt l- 24 ġimgħa tat- terapija.
50 Study 2 also had a drug withdrawal period during which patients who achieved a PASI improvement of at least 50% at week 24 had treatment stopped.
Studju 2 kellu wkoll perijodu fejn il- mediċina ma ngħatatx waqt liem żmien pazjenti li kienu kisbu titjib PASI ta ’ mill- anqas 50% f’ ġimgħa 24 kellhom it- trattament imwaqqaf.
During the withdrawal period, symptoms of psoriasis gradually returned with a median time to disease relapse of 3 months.
Waqt il- perijodu ta ’ żmien fejn ma hadux il- mediċina, sintomi ta ’ psorjasi gradwalment ġew lura bi żmien medjan tar- rikaduta tal- marda ta ’ 3 xhur.
At week 12, more patients randomised to Enbrel had positive efficacy responses (e. g., PASI 75) than those randomised to placebo.
F’ ġimgħa 12, iktar pazjenti li kienu randomised għal Enbrel kellhom risponsi pożittivi tal- effikaċja (eż.
Paediatric Plaque Psoriasis Outcomes at 12 Weeks Enbrel 0.8 mg/ kg Once
49 Riżultati tal- Psorjasi Pedjatrika tal- Plakka f’ Ġimgħa 12 Enbrel 0. 8 mg/ kg Darba fil -
After the 12-week double-blind treatment period, all patients received Enbrel 0.8 mg/ kg (up to 50 mg) once weekly for additional 24 weeks.
Wara l- kura double- blind ta ’ 12- il ġimgħa, il- pazjenti kollha rċivew Enbrel 0. 8 mg/ kg (sa 50 mg) darba f’ ġimgħa għal 34 ġimgħa addizzjonali.
51 Antibodies to Enbrel
Antikorpi għal Enbrel
A biexponential curve is required to describe the concentration time curve of etanercept.
50 Irid ikun hemm kurva biesponenzjali biex tiddeskrivi il- kurva ta ’ konċentrazzjoni vs ħin ta ’ etanercept.
Additionally, the pharmacokinetics of Enbrel in rheumatoid arthritis patients, ankylosing spondylitis and plaque psoriasis patients are similar.
Il- farmakokinetiċi ta ’ Enbrel f’ pazjenti bl- artrite rewmatojde, f’ pazjenti b’ immobilità tal- vertebra kawża ta ’ infjammazzjoni u psorjasi tal- plakka huma simili.
Mean serum concentration profiles at steady state in treated RA patients were Cmax of 2.4 mg/ l vs 2.6 mg/ l, Cmin 1.2 mg/ l vs 1.4 mg/ l and partial AUC of 297 mgh/ l vs 316 mgh/ l for 50 mg Enbrel once weekly (n=21) vs 25 mg Enbrel twice weekly (n=16), respectively.
Profili medji tal- konċentrazzjoni fis- serum fi stat fiss f’ pazjenti b’ RA ittrattati kienu Cmax ta ’ 2. 4 mg/ l vs 2. 6 mg/ l, Cmin ta ’ 1. 2 mg/ l vs 1. 4 mg/ l, u AUC parzjali of 297 mgh/ l vs 316 mgh/ l għal 50 mg Enbrel darba fil- ġimgħa (n=21) vs 25 mg Enbrel darbtejn fil- ġimgħa (n=16), rispettivament.
In an open-label, single-dose, two- treatment, crossover study in healthy volunteers, etanercept administered as a single 50 mg/ ml injection was found to be bioequivalent to two simultaneous injections of 25 mg/ ml.
Fi studju open- label, single- dose, two- treatment, crossover f’ voluntiera f’ saħħithom, etanercept mogħti bħala injezzjoni waħdanija ta ’ 50 mg/ ml instab li kien bijoekwivalenti għal żewġ injezzjonijiet simultanji ta ’ 25 mg/ ml.
52 Although there is elimination of radioactivity in urine after administration of radiolabelled etanercept to patients and volunteers, increased etanercept concentrations were not observed in patients with acute renal or hepatic failure.
Għalkemm hemm l- eliminazzjoni ta ’ radioattività fl- awrina wara t- tehid ta ’ etanercept immarkat b’ sustanza radju- attiva f’ pazjenti u f’ voluntiera, ma gietx osservata żieda fil- konċentrazzjonijiet ta ’ etanercept f’ pazjenti b’ insuffiċjenza renali jew epatika akuta.
In a polyarticular juvenile idiopathic arthritis trial with Enbrel, 69 patients (aged 4 to 17 years) were administered 0.4 mg Enbrel/ kg twice weekly for three months.
Fi studji b’ Enbrel fuq 69 pazjent (ta ’ eta` ta ’ bejn 4 u 17- il sena) bl- artrite idjopatika tal- minorenni ġ b’ kors poliartikulari, 0. 4 mg/ kg Enbrel kien mogħti darbtejn f’ ġimgħa għal tliet xhur.
The youngest children (4 years of age) had reduced clearance (increased clearance when normalised by weight) compared with older children (12 years of age) and adults.
L - iżgħar tfal (ta ’ 4 snin) kellhom clearance mnaqqas (hemm żieda ta ’ clearance meta mkejjel bl- użin) meta mqabbla ma ’ tfal akbar (ta ’ tnax- il sena) u ma ’ adulti.
5.3 Preclinical safety data
51 5. 3 Tagħrif ta 'qabel l- użu kliniku dwar is- sigurtà tal- mediċina
Enbrel did not elicit dose-limiting or target organ toxicity in cynomolgus monkeys following twice weekly subcutaneous administration for 4 or 26 consecutive weeks at a dose (15 mg/ kg) that resulted in AUC-based serum drug concentrations that were over 27-fold higher than that obtained in humans at the recommended dose of 25 mg.
Enbrel ma kkawżax xi limitazzjoni ta ’ doża jew tossiċità f’ xi organu magħżul fix- xadini tat- tip cynomolgus wara li ngħataw injezzjonijiet taħt il- ġilda darbtejn fil- ġimgħa għal 4 jew 26 ġimgħa konsekkutiva b’ doża (15 mg/ kg) li rriżultat f’ konċentrazzjoni tad- droga fis- serum ibbażata fuq AUC li kienu aktar minn 27 darba aktar minn dak miksub fil- bniedem b’ doża rrakkomandata ta ’ 25mg.
Mannitol Sucrose Trometamol
Mannitol Sukkrozju Trometamol.
After reconstitution, immediate use is recommended.
Wara li jiġi rikostitwit, l- użu immedjat tal- prodott hu rrakkomandat.
Chemical and physical stability has been demonstrated for 48 hours at 2 – 8 C.
Stabbilità kimika jew fiżika ntweriet għal 48 siegħa f' temperatura ta '2°C – 8°C.
If not used immediately, storage times are the responsibility of the user and should normally not be longer than 6 hours at 2 – 8 C, unless reconstitution has taken place in controlled and validated aseptic conditions.
Jekk ma jintużax minnufih, il- ħinijiet ta 'ħażna huma r- responsabiltà ta' l- utent u m’ għandhomx ikunu ta ’ aktar minn 6 sigħat f' temperatura ta '2°C - 8°C, ħlief meta r- rikostituzzjoni ssir f' kundizzjonijiet asettiċi kontrollati u validati.
Do not freeze.
Tagħmlux fil- friża
Cartons contain 4 vials of Enbrel with 8 alcohol swabs.
Pakett fih 4 fjali ta ’ Enbrel u 8 swabs bl- alkoħol.
Enbrel is reconstituted with 1 ml water for injections before use, and administered by subcutaneous injection.
52 Enbrel hu rikostitwit b’ 1 ml ilma għall- injezzjonijiet qabel jintuża, u jiġi mogħti b' injezzjoni subkutaneja.
The solution should be clear and colourless to pale yellow with no lumps, flakes or particles.
Is - soluzzjoni għandha tkun ċara u bla kulur għal isfar ċar, bla għoqod, biċċiet jew frak.
Start again with another vial.
Erġa ibda mill- ġdid b ’ kunjettġdid.
Each vial contains 25 mg of etanercept.
Kull fjala fiha 25 mg ta ’ etanercept.
56 Polyarticular juvenile idiopathic arthritis
Artrite idjopatika poliartikolari tal- minorenni
Psoriatic arthritis
54 Artrite psorjatika
Treatment of active and progressive psoriatic arthritis in adults when the response to previous disease- modifying antirheumatic drug therapy has been inadequate.
Il- kura ta ’ l- artrite psorjatika attiva u progressiva f’ adulti meta r- rispons ma kienx adekwat meta ngħataw terapija b’ mediċini anti- rewmatiċi li jimmodifikaw il- marda.
Treatment of adults with severe active ankylosing spondylitis who have had an inadequate response to conventional therapy.
Il- kura f’ adulti li għandhom ankylosing spondylitis severa w attiva u li kellhom rispons mhux adekwat għat- terapija konvenzjonali.
Alternatively, 50 mg administered once weekly has been shown to be safe and effective (see section 5.1).
B’ mod alternattiv, intwera li 50 mg mogħtija darba fil- ġimgħa ntwera li huma siguri u effettivi (ara sezzjoni 5. 1).
57 Plaque psoriasis
Psorjasi tal- plakka
Alternatively, 50 mg given twice weekly may be used for up to 12 weeks followed, if necessary, by a dose of 25 mg twice weekly or 50 mg once weekly.
B’ mod alternattiv, intwera li tista ’ tingħata doża ta ’ 50 mg darbtejn fil- ġimgħa sa 12- il ġimgħa, segwita minn, jekk meħtieġ, doża ta ’ 25 mg darbtejn fil- ġimgħa jew 50 mg darba fil- ġimgħa.
Treatment with Enbrel should continue until remission is achieved, for up to 24 weeks.
55 Trattament b’ Enbrel għandu jitkompla sakemm ikun hemm titfija, sa żmien 24 ġimgħa.
If re-treatment with Enbrel is indicated, the above guidance on treatment duration should be followed.
Jekk trattament mill- ġdid b’ Enbrel huwa indikat, il- gwida ta ’ hawn fuq dwar it- trattament għandha tiġi segwita.
58 4.4 Special warnings and precautions for use
4. 4 Avviżi speċjali u prekawzjonijiet speċjali għall- użu
In evaluating patients for infections, the patient’ s risk for relevant opportunistic infections (e. g., exposure to endemic mycoses) should be considered.
Fl- evalwazzjoni ta ’ pazjenti għal infezzjonijiet, ir- riskju tal- pazjent għal infezzjonijiet opportunistiċi rilevanti (eż. espożizzjoni għal mikożi endemika) għandu jiġi kkunsidrat.
Patients who develop a new infection while undergoing treatment with Enbrel should be monitored closely.
56 Pazjenti li jiżviluppaw infezzjoni ġdida waqt li jkunu qed jieħdu kura b’ Enbrel għandhom jiġu osservati sewwa.
Physicians should exercise caution when considering the use of Enbrel in patients with a history of recurring or chronic infections or with underlying conditions that may predispose patients to infections such as advanced or poorly controlled diabetes.
It- tobba għandhom ikunu attenti meta jirrakkomandaw l- użu ta ’ Enbrel f’ pazjenti b’ passat ta ’ infezzjonijiet li jitfaċċaw minn żmien għall- ieħor, jew f’ pazjenti b’ infezzjonijiet kroniċi, jew f’ pazjenti li għandhom kundizzjonijiet moħbija li jistgħu jżidu r- riskju għall- infezzjonijiet, per eżempju d - dijabete avvanzata jew mhux ikkontrollata bil- għaqal.
It is recommended that the conduct of these tests should be recorded in the patient’ s alert card.
Hu rrakkomandat li d- data ta ’ meta jsiru dawn testijiet għandha tkun irreġistrata fil - patient’ s alert card.
59 Worsening of hepatitis C
Aggravament ta ’ epatite Ċ
Concurrent Enbrel and abatacept treatment
57 Il- kura b’ Enbrel u abatacept fl- istess ħin
Allergic reactions
Reazzjonijiet Allerġiċi
60 In the controlled portions of clinical trials of TNF-antagonists, more cases of lymphoma have been observed among patients receiving a TNF-antagonist compared with control patients.
Fil- partijiet ikkontrollati ta ’ l- istħarriġ kliniku ta ’ antagonisti għal TNF, aktar każijiet ta ’ limfomi ġew osservati fost pazjenti li qed jieħdu antagonisti għal TNF meta mqabbla ma ’ pazjenti kontroll.
With the current knowledge, a possible risk for the development of lymphomas or other malignancies in patients treated with a TNF-antagonist cannot be excluded.
Bit- tagħrif attwali, riskju possibli għall- iżvilupp ta ’ limfomi u tumuri malinni oħra f’ pazjenti ttrattati b’ antagonisti għal TNF ma jistax jiġi eskluż.
No data are available on the secondary transmission of infection by live vaccines in patients receiving Enbrel.
M’ hemm l- ebda tagħrif dwar transmissjoni sekondarja ta ’ infezzjonijiet minn vaċċini ħajjin f’ pazjenti li jieħdu Enbrel.
In a double blind, placebo controlled, randomised clinical study in adult patients with psoriatic arthritis 184 patients also received a multivalent pneumococcal polysaccharide vaccine at week 4.
Huwa rakkomandat li pazjenti b’ artrite idjopatika tal- minorenni, jekk huwa possibbli, jiġu aġġornati mat - tilqim kollu skond il- linji gwida tat- tilqim attwali qabel tinbeda terapija b’ Enbrel Fi studju kliniku randomizzat, double blind, ikkontrollat bi plaċebo f’ pazjenti adulti b’ artrite psorjatika, 184 pazjenti ngħataw ukoll multivalent pneumococcal polysaccharide vaccine fir- 4 ġimgħa.
In this study most psoriatic arthritis patients receiving Enbrel were able to mount effective B-cell immune response to pneumococcal polysaccharide vaccine, but titers in aggregate were moderately lower and few patients had two-fold rises in titers compared to patients not receiving Enbrel.
F’ dan l- istudju l- parti l- kbira tal- pazjenti b’ artrite psorjatika li kienu qed jingħataw Enbrel kienu kapaċi jibnu rispons immunoloġiku effettiv taċ- ċelloli B għal pneumococcal polysaccharide vaccine, iżda t- titrati miġbura flimkien kienu moderatament aktar baxxi u ftit pazjenti kellhom żidiet ta 'darbtejn fit- titrati mqabblin ma ’ pazjenti li mhux qegħdin jieħdu Enbrel.
Autoantibody formation
58 Formazzjoni awtoantikorpi
Haematologic reactions
Reazzjonijiet Ematoloġiċi
All patients and parents/ caregivers should be advised that if the patient develops signs and symptoms suggestive of blood dyscrasias or infections (e. g., persistent fever, sore throat, bruising, bleeding, paleness) whilst on Enbrel, they should seek immediate medical advice.
Il- pazjenti kollha u l- ġenituri/ dawk li jieħdu ħsiebhom għandom jingħataw parir li jekk il- pazjent jiżviluppa sinjali jew sintomi li jissuġġerixxu mard fiċ- ċelluli tad- demm jew infezzjonijiet (eż. deni persistenti, uġigħ fil- grieżem, tbenġil, fsada, sfurija), għandhom ifittxu minnufih parir mediku.
There have been rare reports of CNS demyelinating disorders in patients treated with Enbrel (see section 4.8).
Mard tas- CNS Rapporti dwar pazjenti kkurati b’ Enbrel u li kellhom mard demajelinanti tas- CNS huma rari (ara sezzjoni 4. 8).
Although no clinical trials have been performed evaluating Enbrel therapy in patients with multiple sclerosis, clinical trials of other TNF antagonists in patients with multiple sclerosis have shown increases in disease activity.
Għalkemm ma sar l- ebda studju kliniku biex jevalwa t- terapija ta ’ Enbrel f’ pazjenti bi sklerożi multipla, studji kliniċi ta ’ antagonisti oħra tat- TNF f’ pazjenti bi sklerożi multipla, urew żieda fl- attività tal- marda.
A careful risk/ benefit evaluation, including a neurological assessment, is recommended when prescribing Enbrel to patients with pre-existing or recent onset of CNS demyelinating disease, or to those who are considered to have an increased risk of developing demyelinating disease.
Evalwazzjoni serja tar- riski/ benefiċċi, flimkien ma ’ assessjar newroloġiku, hu rrakkomandat meta Enbrel tingħata f’ pazjenti li diġa kellhom jew qabadhom riċentement mard demajelinanti tas- CNS, jew f’ dawk li huma kkunsidrati li għandhom riskju ogħla li jiżviluppaw mard demajelinanti.
In a controlled clinical trial of two years duration in rheumatoid arthritis patients, the combination of Enbrel and methotrexate did not result in unexpected safety findings, and the safety profile of Enbrel when given in combination with methotrexate was similar to the profiles reported in studies of Enbrel and methotrexate alone.
Terapija flimkien ma ’ mediċini oħra Fi studji kliniċi kkontrollati li damu sejrin sentejn fuq pazjenti b’ artrite rewmatojde, l- għoti ta ’ Enbrel flimkien ma ’ methotrexate ma rriżultax f’ sejbiet ta ’ sigurtà mhux mistennija, u l- profil tas- sigurtà ta ’ Enbrel meta mogħti flimkien ma ’ methotrexate kien simili għal profili li ġew irrappurtati fl- istudji b’ Enbrel u methotrexate waħedhom.
The long-term safety of Enbrel in combination with other disease-modifying antirheumatic drugs (DMARD) has not been established.
Is- sigurtà fit- tul ta ’ Enbrel flimkien ma ’ mediċini oħra anti- rewmatiċi li jimmodifikaw il- marda (DMARD) għadu ma ġiex stabbilit.
61 The use of Enbrel in combination with other systemic therapies or phototherapy for the treatment of psoriasis has not been studied.
L- użu ta ’ Enbrel flimkien ma ’ terapiji sistemiċi oħrajn jew fototerapija għat- trattament ta ’ psorjasi ma ġiex mistħarreġ.
Based on pharmacokinetic data (see section 5.2), no dosage adjustment is needed in patients with renal or hepatic impairment; clinical experience in such patients is limited.
Indeboliment renali u epatiku Meta tibbaża fuq tagħrif farmakonetiku (ara sezzjoni 5. 2), mhux meħtieġ l- ebda tibdil fid- doża f’ pazjenti b’ indeboliment renali jew epatiku; l- esperjenza klinika f’ dawn il- pazjenti hi limitata.
Physicians should use caution when using Enbrel in patients who have congestive heart failure (CHF).
Insuffiċjenza tal- qalb konġestiva It- tobba għandhom jkunu attenti meta jużaw Enbrel f’ pazjenti li għandhom insuffiċjenza tal- qalb konġestiva (CHF).
The incidence of non-cutaneous malignancies of various types was significantly higher in patients treated with Enbrel than in the control group.
L- inċidenza ta ’ tumuri malinni mhux tal- ġilda ta ’ tipi varji kienet sinifikattivament ogħla għal pazjenti ttrattati b’ Enbrel milli għall - grupp ta ’ kontroll.
4.5 Interaction with other medicinal products and other forms of interaction
59 4. 5 Prodotti mediċinali oħra li ma jaqblux ma ’ dan il- prodott u affarjiet oħra li jistgħu jibdlu l- effett farmaċewtiku tal- prodott
62 Non-interactions
Non- interazzjonijiet
4.8 Undesirable effects
60 4. 8 Effetti mhux mixtieqa
The proportion of patients who discontinued treatment due to adverse events was the same in both the Enbrel and placebo treatment groups; in the first active-controlled trial, the dropout rate was significantly higher for methotrexate (10%) than for Enbrel (5%).
Il- proporzjon tal- pazjenti li ma komplewx il- kura minħabba avvenimenti avversi kienu l- istess kemm fil- grupp ta ’ Enbrel kif ukoll fil- grupp tal- plaċebo; fl- ewwel studju kkontrollat attivament, in- numru ta ’ pazjenti li waqqfu t- terapija kien sinjifikament aktar għoli għal methotrexate (10%) minn dak għal Enbrel (5%).
In the second active-controlled trial, the rate of discontinuation for adverse events after 2 years of treatment was similar among all three treatment groups, Enbrel (16%), methotrexate (21%) and Enbrel in combination with methotrexate (17%).
Fit- tieni studju kkontrollat attivament, ir- rata ta ’ pazjenti li waqqfu t- terapija wara sentejn ta ’ trattament minħabba avvenimenti avversi kienet simili għat- tliet gruppi ta ’ kura, Enbrel (16%), methotrexate (21%) u Enbrel flimkien ma ’ methotrexate (17%).
Additionally, Enbrel has been studied in240 psoriatic arthritis patients who participated in 2 double-blind placebo-controlled studies and an open-label extension study.
Barra minn hekk, Enbrel kien studjat f’ 240 pazjent bl- artrite psorjatika li ħadu sehem f’ 2 studji double- blind u kkontrollati bi plaċebo u fi studju ieħor ta ’ estensjoni open- label.
Five hundred and eight (508) ankylosing spondylitis patients were treated with Enbrel in 4 double-blind placebo-controlled studies.
Ħames mija u tmien pazjenti (508) b’ ankylosing spondylitis ħadu kura b’ Enbrel f’ 4 studji double- blind u kkontrollati bi plaċebo.
Enbrel has also been studied in 1,180 patients with plaque psoriasis for up to 6 months in 4 double-blind placebo- controlled studies.
Enbrel ġie mistħarreġ ukoll f’ 1, 180 bi psorjasi tal- plakka sa żmien 6 xhur f’ 4 studji double - blind ikkontrollati bi plaċebo.
Among patients with rheumatoid arthritis treated in
Fi studji kliniċi double- blind fejn Enbrel ġie mqabbel ma ’ plaċebo, reazzjonijiet fis- siti ta ’ l- injezzjoni kienu l- avvenimenti avversi l- aktar frekwenti f’ pazjenti li ħadu Enbrel.
63 placebo-controlled trials, serious adverse events occurred at a frequency of 4% in 349 patients treated with Enbrel compared with 5% of 152 placebo-treated patients.
Fi studji kkontrollati bi plaċebo, fost il- pazjenti bl- artrite rewmatojde kkurati, avvenimenti avversi serji seħħew bi frekwenza ta ’ 4% f’ 349 pazjent ikkurati b’ Enbrel, imqabbla ma ’ 5% f’ 152 pazjent ikkurati bil- plaċebo.
In the second active-controlled trial the rate of serious adverse events after 2 years of treatment was similar among the three treatment groups (Enbrel 16%, methotrexate 15% and Enbrel in combination with methotrexate 17%).
Fit- tieni studju kkontrollat attivament wara sentejn ta ’ trattament, ir- rata ta ’ avvenimenti avversi kienet simili għat- tliet gruppi ta ’ kura (Enbrel 16%, methotrexate 15% u Enbrel flimkien ma ’ methotrexate 17%).
Within the organ system classes, adverse reactions are listed under headings of frequency (number of patients expected to experience the reaction), using the following categories: very common (> 1/ 10); common (> 1/ 100 ,< 1/10); uncommon (> 1/1000 ,< 1/100); rare (> 1/10,000, < 1/ 1000); very rare (< 1/10 ,000); not known (could not be accurately estimated through clinical studies).
Fost il- klassijiet tas- sistema ta ’ l- organi, ir- risponsi avversi huma elenkati skond il- frekwenza (numru ta ’ pazjenti mistennija li jesperjenzaw ir- rispons) skond dawn il- kategoriji: komuni ħafna (> 1/ 10); komuni (> 1/ 100, < 1/ 10); mhux komuni (> 1/ 1000, < 1/ 100); rari (> 1/ 10, 000, < 1/ 1000); rari ħafna (< 1/ 10, 000); mhux magħrufa (ma jisgħux ikunu stmati bi preċiżjoni minn studji kliniċi).
Immune system disorders:
61 Disturbi fis- sistema immuni:
Allergic reactions (see Skin and subcutaneous tissue disorders), autoantibody formation* Serious allergic/ anaphylactic reactions (including angioedema, bronchospasm) Macrophage activation syndrome*, anti-neutrophilic cytoplasmic antibody positive vasculitis
Reazzjonijiet allerġiċi/ anafilattiċi serji (inklużi anġjoedema, bronkospażmu) Sindrome ta ’ l- attivazzjoni tal- makrofagu *, vaskulite pożittiva ta ’ l- antikorpi
64 Skin and subcutaneous tissue disorders:
Disturbi fil- ġilda u fit- tessuti ta ’ taħt il- ġilda:
*see Additional information, below.
* ara aktar informazzjoni ta ’ hawn taħt
Additional information
62 Informazzjoni addizzjonali
Among rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and plaque psoriasis patients in placebo-controlled, active-controlled, and open-label trials of Enbrel, serious adverse events reported included malignancies (see below), asthma, infections (see below), heart failure, myocardial infarction, myocardial ischaemia, chest pain, syncope, cerebral ischaemia, hypertension, hypotension, cholecystitis, pancreatitis, gastrointestinal haemorrhage, bursitis, confusion, depression, dyspnoea, abnormal healing, renal insufficiency, kidney calculus, deep vein thrombosis, pulmonary embolism, membranous glomerulonephropathy, polymyositis, thrombophlebitis, liver damage, leucopenia, paresis, paresthesia, vertigo, allergic alveolitis, angioedema, scleritis, bone fracture, lymphadenopathy, ulcerative colitis, intestinal obstruction, eosinophilia, haematuria, and sarcoidosis.
Fost il- pazjenti bl- artrite rewmatojde, bl- artrite psorjatika, u bl- immobilità tal- vertebra kawża ta ’ infjammazzjoni u psorjasi tal- plakka fi studji kkontrollati bi plaċebo, ikkontrollati attivament u open - label b’ Enbrel, ġew rrappurtati reazzjonijiet avversi serji inklużi tumuri malinni (ara taħt), ażma, infezzjonijiet, (ara taħt) insuffiċjenza tal- qalb, infart mijokardijaku, iskemja mijokardijaka, uġigħ fis - sider, sinkope, iskemja ċerebrali, pressjoni għolja, pressjoni baxxa, koleċistite, pankreatite, ħemoraġija gastrointestinali, burżite, konfużjoni, dipressjoni, dispneja, fejqan annormali, insuffiċjenza renali, ġebla fil- kliewi, trombożi fil- vini fondi, emboliżmu pulmonari, nefropatija glomerulari fir- riti, polimijosite, tromboflebite, ħsara fil- fwied, lewkopenja, pareżi, paresteżja, sturdament, alveolite allerġika, anġjoedema, sklerite, ksur fl- għadam, limfadenopatija, kolite ulċerativa u ostruzzjoni fl - imsaren, eosinofilja, ematurja, u sarkojdożi.
In clinical studies conducted for more than 2 years with 351 ankylosing spondylitis patients, 6 malignancies were reported in Enbrel-treated patients.
Fi studji kliniċi magħmula għal aktar minn sentejn b’ 351 pazjent b’ ankylosing spondylitis, 6 tumuri malinni kienu rrappurtati f’ pazjenti ttrattati b’ Enbrel.
65 There were a total of 15 lymphomas reported in 5,966 patients treated with Enbrel in rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and psoriasis clinical trials.
Kien hemm total ta ’ 15- il limfoma rrappurtati f’ 5966 pazjent ittrattati b’ Enbrel fi provi kliniċi f’ artrite rewmatojde, artrite psorjatika, ankylosing spondylitis u psorjasi.
Mean duration was approximately 3 to 5 days.
Iż- żmien medju ta ’ kemm damet ir- rispons kienet ta ’ bejn wieħed u ieħor 3 għal 5 ijiem.
Additionally, some patients developed recall injection site reactions characterised by a skin reaction at the most recent site of injection along with the simultaneous appearance of injection site reactions at previous injection sites.
Addizzjonalment, xi ftit pazjenti żviluppaw mill- ġdid reazzjonijiet fis- siti ta ’ l- injezzjoni kkaratterizzati b’ rispons tal- ġilda fis- siti ta ’ l- injezzjoni l- aktar riċenti flimkien mad- dehra simultanja ta ’ reazzjonijiet fis- siti ta ’ l - injezzjoni f’ sit ta ’ injezzjonjiet li ngħataw qabel.
These reactions were generally transient and did not recur with treatment.
Dawn ir- risponsi ġeneralment kienu għal żmien qasir, u bil- kura ma reġgħux dehru.
In controlled trials in patients with plaque psoriasis, approximately 14.5% of patients treated with Enbrel developed injection site reactions compared with 5.2% of placebo-treated patients during the first 12 weeks of treatment.
Fi provi kontrollati f’ pazjenti bi psorjasi tal- plakka, bejn wieħed u ieħor 14. 5% tal- pazjenti ttrattati b’ Enbrel żviluppaw reazzjonijiet fis- siti tat- titqiba meta mqabbla ma ’ 5. 2% ta ’ pazjenti ttrattati bi plaċebo waqt l- ewwel 12- il ġimgħa tat- trattament.
In placebo-controlled trials, no increase in the incidence of serious infections (fatal, life threatening, or requiring hospitalisation or intravenous antibiotics) was observed.
Fi studji kkontrollati bil- plaċebo fejn ġie evalwat Enbrel, l- ebda żieda ta ’ inċidenza ta ’ infezzjonijiet serji (fatali, ta ’ theddid għall- ħajja, jew li kien hemm il- bżonn li jiddaħħlu l- isptar jew jingħataw injezzjoniet ta ’ antibijotiċi ġol- vini għalihom) ma ġew osservati.
Serious infections occurred in 6.3% of rheumatoid arthritis patients treated with Enbrel for up to 48 months.
Infezzjonijiet serji seħħew f’ 6. 3% tal - 63 pazjenti bl- artrite rewmatojde kkurati b’ Enbrel sa 48 xhur.
In the 2-year active-controlled study where patients were treated with either Enbrel alone, methotrexate alone or Enbrel in combination with methotrexate, the rates of serious infections were similar among the treatment groups.
Fi studju ta ’ sentejn kkontrollat attivament fejn il- pazjenti kienu kkurati jew b’ Enbrel waħdu, jew b’ methotrexate waħdu jew b’ Enbrel flimkien ma ’ methotrexate, ir- rata ta ’ infezzjonijiet serji kienet simili fost il- gruppi li ġew ikkurati.
Some have occurred within a few weeks after initiating treatment with Enbrel in patients who have underlying conditions (e. g. diabetes, congestive heart failure, history of active or chronic infections) in addition to their rheumatoid arthritis (see section 4.4).
Xi uħud ġraw fi ftit ġimgħat wara li bdiet il- kura b’ Enbrel f’ pazjenti li kellhom ukoll mard ieħor (eż. dijabete, insuffiċjenza tal- qalb konġestiva, passat ta ’ infezzjonijiet attivi jew kroniċi) flimkien ma ’ l- artite rewmatojde tagħhom (ara sezzjoni 4. 8).
The proportion of patients treated with Enbrel who developed anticardiolipin antibodies was similarly increased compared to placebo-treated patients.
Il- proporzjon tal - pazjenti kkurati b’ Enbrel li żviluppaw antikorpi tat- tip anti- kardjolipin kellhom l- istess żieda meta mqabbel ma ’ pazjenti kkurati bil- plaċebo.
There have been postmarketing reports of pancytopenia and aplastic anaemia, some of which had fatal outcomes (see section 4.4).
Wara li Enbrel ħareġ fuq is- suq, kien hemm rapporti ta ’ panċitopenja u anemija aplastika, li x’ uħud minnhom spiċċaw biex kienu fatali (ara sezzjoni 4. 4).
Interstitial lung disease
64 Mard interstizjali tal- pulmun
Laboratory evaluations
Evalwazzjoni fil- Laboratorju
Undesirable effects in paediatric patients with polyarticular juvenile idiopathic arthritis
Effetti mhux mixtieqa f’ pazjenti pedjatriċi bl- artrite idjopatika poliartikolari minorenni
67 The types of infections seen in clinical trials in juvenile idiopathic arthritis patients aged 2 to 18 years were generally mild to moderate and consistent with those commonly seen in outpatient paediatric populations.
It- tipi ta ’ infezzjonijiet murija fi provi kliniċi f’ pazjenti b’ artrite idjopatika tal- minorenni ta ’ etajiet bejn 2 sa 18- il sena kienu ġeneralment ħfief għal moderati u konsistenti ma ’ dawk li komunament jidhru fil- popolazzjonijiet pedjatriċi outpatient.
4.9 Overdose
65 4. 9 Doża eċċessiva
Tumor Necrosis Factor alpha (TNF-α) inhibitors.
Inibituri tal- Fattur tan- Nekrosi tat- Tumur (TNF- α).
68 TNF and lymphotoxin exist predominantly as homotrimers, with their biological activity dependent on cross-linking of cell surface TNFRs.
TNF u lymphotoxin jinstabu l- aktar bħala homotrimers, li l- attività bijoloġika tagħhom hija dipendenti fuq “ cross- linking ” ma ’ TNFRs fuq is- superfiċje taċ- ċelluli.
This section presents data from four randomised controlled trials in adults with rheumatoid arthritis, one study in polyarticular juvenile idiopathic arthritis, one study in adults with psoriatic arthritis, one study in adults with ankylosing spondylitis, one study in paediatric patients with plaque psoriasis, and four studies in adults with plaque psoriasis.
Din is- sezzjoni fiha tagħrif meħud minn erba ’ studji randomised u kkontrollati f’ adulti b’ artrite rewmatojde; studju wieħed ta ’ pazjenti b’ artrite idjopatika tal- minonorennitat- tip poliartikulari, studju wieħed ta ’ adulti b’ artrite psorjatika, u studju wieħed ta ’ adulti b’ immobilità tal- vertebra kawża ta ’ infjammazzjoni, studju wieħed fuq pazjenti pedjatriċi bi psorjasi tal- plakka, u erba ’ studji ta ’ adulti bi psorjasi tal- plakka.
Adult patients with rheumatoid arthritis
66 Pazjenti adulti b’ artrite rewmatojde
The efficacy of Enbrel was assessed in a randomised, double-blind, placebo-controlled study.
L- effikaċja ta ’ Enbrel ġiet imkejla fi studju randomised, double- blind u kkontrollat bi plaċebo.
Enbrel 41% and 40%, placebo 8% and 5% at months 3 and 6 respectively; p < 0.01 Enbrel vs Placebo at all time points for both ACR 20 and ACR 50 responses).
Enbrel 41% u 40%, placebo 8% u 5% f ’ 3 u f’ 6 xhur rispettivament; p < 0. 01 Enbrel vs plaċebo f’ kull punt taż- żmien għar- rispons ta ’ ACR 20 kif ukoll ACR 50.
Re-introduction of treatment with Enbrel after discontinuations of up to 24 months resulted in the same magnitudes of responses as patients who received Enbrel without interruption of therapy based on results of open-label studies.
Meta reġgħet inbdiet il- kura b’ Enbrel wara li ma tkomplietx sa 24 xahar irriżulta fl- istess qawwa ta ’ risponsi bħal dawk tal- pazjenti li komplew jieħdu Enbrel mingħajr interruzzjoni tat- terapija li kienet ibbażata fuq ir- riżultati ta ’ studji open- label.
The efficacy of Enbrel was compared to methotrexate in a third randomised, active-controlled study with blinded radiographic evaluations as a primary endpoint in 632 adult patients with active rheumatoid arthritis (< 3 years duration) who had never received treatment with methotrexate.
L- effikaċja ta ’ Enbrel kien imqabbel ma ’ methotrexate fi studju randomised, ikkontrollat attivament b’ evalwazzjonijiet radjografiċi blinded bħala endpoint primarju fi 632 pazjent adult bl- artrite rewmatojde attiva (għal < 3 snin) u li qatt ma kienu ħadu kura b’ methotrexate.
The results are shown in the figure below.
Ir- riżultati jidhru fil- figuri ta ’ hawn taħt.
RADIOGRAPHIC PROGRESSION:
67 PROGRESSJONI RADJOGRAFIKA:
In another active-controlled, double-blind, randomised study, clinical efficacy, safety, and radiographic progression in RA patients treated with Enbrel alone (25 mg twice weekly), methotrexate alone (7.5 to 20 mg weekly, median dose 20 mg), and of the combination of Enbrel and methotrexate initiated concurrently were compared in 682 adult patients with active rheumatoid arthritis of 6 months to 20 years duration (median 5 years) who had a less than satisfactory response to at least 1 disease-modifying antirheumatic drug (DMARD) other than methotrexate.
Fi studju ieħor ikkontrollat attivament, double- blind u randomised, l- effikaċja klinika, is- sigurtà, u l - progressjoni radjografika f’ pazjenti b’ RA kkurati b’ Enbrel waħdu (25 mg darbtejn f’ ġimgħa) b’ methotrexate waħdu (7. 5 sa 20 mg fil- ġimgħa, b’ doża medja ta ’ 20 mg), u Enbrel mibdi flimkien ma ’ methotrexate ġew imqabbla f’ 682 pazjent adult b’ artrite rewmatojde attiva ta ’ bejn 6 xhur u 20 sena (medjan 5 snin) li kellhom rispons anqas minn sodisfaċenti għal mill- anqas waħda mill- mediċina anti- rewmatojde li timmodifika l- marda barra methotrexate.
70 Patients in the Enbrel in combination with methotrexate therapy group had significantly higher ACR 20, ACR 50, ACR 70 responses and improvement for DAS and HAQ scores at both 24 and 52 weeks than patients in either of the single therapy groups (results shown in table below).
Il- pazjenti fil- grupp ta ’ Enbrel flimkien mat- terapija ta ’ methotrexate kellhom risponsi sinjifikament aktar għolja ta ’ ACR 20, ACR 50, ACR 70 u titjib fl- iskor tad- DAS u HAQ kemm f’ 24 kif ukoll f’ 52 ġimgħa minn pazjenti li kienu fil- gruppi ta ’ terapija b’ mediċina waħda (ir- riżultati jidhru fit- tabella ta ’ hawn taħt).
CLINICAL EFFICACY RESULTS AT 12 MONTHS:
68 RIŻULTATI TA ’ L- EFFIKAĊJA KLINIKA WARA 12- IL XAHAR:
2.3† ,
5. 7 3. 0 18%
37 %† ,
1. 7
Radiographic progression at 12 months was significantly less in the Enbrel group than in the methotrexate group, while the combination was significantly better than either monotherapy at slowing radiographic progression (see figure below).
Il- progressjoni radjografika wara 12- il xahar kienet sinjifikament anqas fil- grupp ta ’ Enbrel milli l - grupp ta ’ methotrexate, waqt li meta ttieħdu flimkien id- dawmien fil- progressjoni radjografika kienet sinjifikament aħjar milli meta l- mediċini ttieħdu weħidhom (ara t- tabella ta ’ hawn taħt).
71 RADIOGRAPHIC PROGRESSION:
69 PROGRESSJONI RADJOGRAFIKA:
-0.54† ,
- 0. 23 †, φ - 0. 30 † - 0. 5 - 0. 54 †, φ - 1. 0 -- Tgħawwir --
The safety and efficacy of Enbrel were assessed in a two-part study in 69 children with polyarticular juvenile idiopathic arthritis who had a variety of juvenile idiopathic arthritis onset types.
Is- sigurtà u l- effikaċja ta ’ Enbrel ġew assessjati fi studju maqsum f’ żewġ partijiet fejn 69 tfal b’ artrite idjopatika tal- minorenni b’ kors poliartikulari, u li fil- bidu kellhom varjetà ta ’ artrite idjopatika ġuvenili.
Patients aged 4 to 17 years with moderately to severely active polyarticular juvenile idiopathic arthritis refractory to or
Kienu studjati pazjenti ta ’ bejn 4 u 17- il sena b’ artrite idjopatika tal- minorennib’ kors poliartikulari bejn moderata u severament li ma fiqitx b’ methotrexate jew kienet intolleranti għal methotrexate; il- pazjenti tħallew fuq doża stabbli ta ’ mediċini kontra l- infjammazzjoni li mhumiex sterojdi u/ jew fuq prednisone (< 0. 2 mg/ kg/ kuljum jew massimu ta’ 10 mg).
In part 2, patients with a clinical response at day 90 were randomised to remain on Enbrel or receive placebo for four months and assessed for disease flare.
Fit - 70 tieni parti, pazjenti b’ rispons kliniku fid- 90 ġurnata, kienu randomised f’ dawk li kellhom jibqgħu fuq Enbrel u f’ oħrajn biex jirċievu l- plaċebo għal erba ’ xhur u jiġu assessjati għal xi żieda qawwija fl - intensità tal- marda.
Disease flare was defined as a  30% worsening in three of six JRA core set criteria and  30% improvement in not more than one of the six JRA core set criteria and a minimum of two active joints.
Żjieda qawwija fl- intensità tal- marda kien definit bħala ≥ 30% eħżen fi tlieta minn sitta kriterji bażiċi magħżula tal- JRA, u pazjenti b’ ≥ 30% titjib f’ mhux aktar minn waħda minn sitta kriterji bażiċi magħżula tal- JRA u b’ mill- anqas żewġ ġogi attivi.
The efficacy of Enbrel was assessed in a randomised, double-blind, placebo-controlled study in 205 patients with psoriatic arthritis.
L- effikaċja ta ’ Enbrel kienet assessjata f’ 205 pazjenti li kellhom artrite psorjatika fi studju randomised, double- blind u kkontrollat bi plaċebo.
Patients were between 18 and 70 years of age and had active psoriatic arthritis ( 3 swollen joints and  3 tender joints) in at least one of the following forms:
Il- pazjenti kienu bejn it- 18- il u s- 70 sena u kellhom artrite psorjatika attiva (≥ 3 ġogi minfuħin u ≥ 3 ġogi sensittivi) f’ mill- anqas waħda minn dawn il- forom:
(1) distal interphalangeal (DIP) involvement; (2) polyarticular arthritis (absence of rheumatoid nodules and presence of psoriasis); (3) arthritis mutilans; (4) asymmetric psoriatic arthritis; or (5) spondylitis-like ankylosis.
(1) involviment distali interfalanġjali (DIP); (2) artrite poliartkulari (nuqqas ta ’ noduli rewmatojdi u presenza ta ’ psorijażi); (3) artrite mutilans; (4) artrite psorjatika asimmetrika; jew (5) immobilità tal - vertebre li tixbaħ infjammazzjoni.
At the end of the double-blind study, patients could enter a long-term open-label extension study for a total duration of up to 2 years.
Fi tmiem ta ’ l- istudju double- blind, il- pazjenti setgħu jidħlu fi studju fit- tul tat- tip open- label extension, għal żmien totali sa sentejn.
Results are summarised in the Table below.
Ir- riżultati jidhru fil - qosor fit- tabella ta ’ hawn taħt:
73 RESPONSES OF PATIENTS WITH PSORIATIC ARTHRITIS IN PLACEBO-CONTROLLED TRIAL Percent of Patients
71 RISPONSI TA ’ PAZJENTI B’ ARTRITE PSORJATIKA FI STUDJU KKONTROLLAT BI PLAĊEBO% ta ’ Pazjenti Enbrela Plaċebo
The disability index score was significantly improved at all timepoints in psoriatic arthritis patients treated with Enbrel, relative to placebo (p < 0.001).
L- iskor ta ’ l- indiċi tad - diżabilità kien sinjifikament aħjar f’ kull punt ta ’ żmien f’ pazjenti bl- artrite psorjatika ikkurati b’ Enbrel, relatat mal- plaċebo (p < 0. 001).
74 Enbrel treatment resulted in improvement in physical function during the double-blind period, and this benefit was maintained during the longer-term exposure of up to 2 years.
Il- kura b’ Enbrel irriżultat fit- titjib tal- funzjoni fiżika matul il- perjodu double- blind, u dan il- benefiċċju inżamm matul l- espożizzjoni għal tul ta ’ żmien sa sentejn.
No study has been performed in patients with psoriatic arthritis using the 50mg once weekly dosing regimen.
72 Ma sar l- ebda studju fejn intuża r- reġimen ta ’ dożi ta ’ 50 mg darba fil- ġimgħa f’ pazjenti b’ artrite psorjatika.
The efficacy of Enbrel in ankylosing spondylitis was assessed in 3 randomised, double-blind studies comparing twice weekly administration of 25 mg Enbrel with placebo.
L- effikaċja ta ’ Enbrel f’ ankylosing spondylitis kienet assessjata fi 3 studji magħżula b’ mod każwali, double- blind li qabblu l- għoti ta ’ 25 mg Enbrel darbtejn fil- ġimgħa ma ’ plaċebo.
75 RESPONSES OF PATIENTS WITH ANKYLOSING SPONDYLITIS IN A PLACEBO-CONTROLLED TRIAL Percent of Patients
RISPONSI TA ’ PAZJENTI B’ ANKYLOSING SPONDYLITIS FI STUDJU KKONTROLLAT BIL- PLAĊEBO Perċentwali ta ’ Pazjenti
In a fourth study, the safety and efficacy of 50 mg Enbrel (two 25 mg SC injections) administered once weekly vs 25 mg Enbrel administered twice weekly were evaluated in a double-blind, placebo-controlled study of 356 patients with active ankylosing spondylitis.
73 Fir- raba ’ studju, is- sigurtà u l- effikaċja ta ’ 50 mg Enbrel (żewġ injezzjonijiet SC ta ’ 25 mg) mogħtija darba fil- ġimgħa vs 25 mg Enbrel mogħtija darbtejn fil- ġimgħa kienu evalwati fi studju double- blind, ikkontrollat bi plaċebo ta ’ 356 pazjent b’ ankylosing spondylitis attiva.
Patients who “ failed to respond to” in the target population is defined by insufficient response (PASI < 50 or PGA less than good), or worsening of the disease while on treatment, and who were adequately dosed for a sufficiently long duration to assess response with at least each of the three major systemic therapies as available.
Pazjenti li “ fallew milli jirrispondu ” mill- popolazzjoni mmirata huma mfissra b’ risponsi insuffiċjenti (PASI < 50 jew PGA anqas minn tajba) jew deterjorament tal- marda waqt l- għoti tal- kura, u li kienu dożati adegwatament għal tul ta ’ żmien suffiċjenti biex jiġi assessjat ir- rispons b ’ ta ’ lanqas kull waħda mit- tliet terapiji sistemiċi kif jeżistu.
Instead, the safety and efficacy of Enbrel were assessed in four randomised, double-blind, placebo-controlled studies.
Minflok, is- sigurtà u l- effikaċja ta ’ Enbrel kienu assessjati f’ erba ’ studji magħżula b’ mod każwali, double- blind u kkontrollati bi plaċebo.
The primary efficacy endpoint in all four studies was the proportion of patients in each treatment group who achieved the PASI 75 (i. e. at least a 75% improvement in the Psoriasis Area and Severity Index score from baseline) at 12 weeks.
L- endpoint ta ’ l- effikaċja primarja fl - erba ’ studji kollha kien il- proporzjon ta ’ pazjenti f’ kull grupp ta ’ trattament li kisbu PASI 75 (i. e., mill- anqas 75% titjib B’ PUNTEĠĠ tal- Psoriasis Area and Severity Index mil- linja bażi) fit- 12- il ġimgħa.
76 Study 1 was a Phase 2 study in patients with active but clinically stable plaque psoriasis involving  10% of the body surface area that were  18 years old.
Studju 1 kien prova ta ’ Fażi 2 f’ pazjenti bi psorjasi tal- plakka klinikament stabbli imma attiva li tinvolvi ≥ 10% tal- erja tal- wiċċ tal- ġisem li kellhom ≥ 18- il sena.
RESPONSES OF PATIENTS WITH PSORIASIS IN STUDIES 2, 3 AND 4 ------------------Study 2--------------- ---------------Study 3------------- ---------------Study 4-------------
74 REAZZJONIJIET TA ’ PAZJENTI BI PSORJASI FI STUDJI 2, 3 U 4 -------------------- Studju 2 ------------------ ---------------- Studju 3 ------------- ------------- Studju 4 ------------
77 Study 2 also had a drug withdrawal period during which patients who achieved a PASI improvement of at least 50% at week 24 had treatment stopped.
Studju 2 kellu wkoll perijodu fejn il- mediċina ma ngħatatx waqt liem żmien pazjenti li kienu kisbu titjib PASI ta ’ mill- anqas 50% f’ ġimgħa 24 kellhom it- trattament imwaqqaf.
Patients received Enbrel 0.8 mg/ kg (up to 50 mg) or placebo once weekly for 12 weeks.
75 Il- pazjenti rċivew Enbrel 0. 8 mg/ kg (sa 50 mg) jew il- plaċebo darba f’ ġimgħa għal 12- il ġimgħa.
Paediatric Plaque Psoriasis Outcomes at 12 Weeks Enbrel 0.8 mg/ kg Once
Riżultati tal- Psorjasi Pedjatrika tal- Plakka f’ Ġimgħa 12 Enbrel 0. 8 mg/ kg Darba fil -
78 Antibodies to Enbrel
Antikorpi għal Enbrel
After a single subcutaneous dose of 25 mg Enbrel, the average maximum serum concentration observed in healthy volunteers was 1.65  0.66  g/ ml, and the area under the curve was 235  96.6  g hr/ ml.
Wara doża waħda taħt il- ġilda ta ’ Enbrel ta ’ 25 mg, il- medja tal- konċentrazzjoni massima fis- serum osservata f’ voluntiera b’ saħħithom kien 1. 65 ± 0. 66 μg/ ml, u l- erja ta ’ taħt il- kurva
A biexponential curve is required to describe the concentration time curve of etanercept.
Irid ikun hemm kurva biesponenzjali biex tiddeskrivi il- kurva ta ’ konċentrazzjoni vs ħin ta ’ etanercept.
Mean serum concentration profiles at steady state in treated RA patients were Cmax of 2.4 mg/ l vs 2.6 mg/ l, Cmin of 1.2 mg/ l vs 1.4 mg/ l and partial AUC of 297 mgh/ l vs 316 mgh/ l for 50 mg Enbrel once weekly (n=21) vs 25 mg Enbrel twice weekly (n=16), respectively.
Profili medji tal- konċentrazzjoni fis- serum fi stat fiss f’ pazjenti b’ RA ittrattati kienu Cmax ta ’ 2. 4 mg/ l vs 2. 6 mg/ l, Cmin ta ’ 1. 2 mg/ l vs 1. 4 mg/ l, u AUC parzjali of 297 mgh/ l vs 316 mgh/ l għal 50 mg Enbrel darba fil- ġimgħa (n=21) vs 25 mg Enbrel darbtejn fil- ġimgħa (n=16), rispettivament.
In a population pharmacokinetics analysis in ankylosing spondylitis patients the etanercept steady state AUCs were 466  g hr/ ml and 474  g hr/ ml for 50 mg Enbrel once weekly (N= 154) and 25 mg twice weekly (N = 148), respectively.
F’ analiżi farmakokinetika tal- popolazzjoni f’ pazjenti b’ ankylosing spondylitis l- AUCs ta ’ stat fiss ta ’ etanercept kienu 466 μg* hr/ ml u 474 μg* h/ ml għal 50 mg Enbrel darba fil- ġimgħa (N= 154) u 25 mg darbtejn fil- ġimgħa (N = 148), rispettivament.
79 Although there is elimination of radioactivity in urine after administration of radiolabelled etanercept to patients and volunteers, increased etanercept concentrations were not observed in patients with acute renal or hepatic failure.
Għalkemm hemm l- eliminazzjoni ta ’ radioattività fl- awrina wara t- tehid ta ’ etanercept immarkat b’ sustanza radju- attiva f’ pazjenti u f’ voluntiera, ma gietx osservata żieda fil- konċentrazzjonijiet ta ’ etanercept f’ pazjenti b’ insuffiċjenza renali jew epatika akuta.
These mean concentrations were similar to those seen in adult patients with plaque psoriasis treated with 25 mg etanercept twice weekly.
Dawn il- konċentrazzjonijiet 77 medji kienu simili għal dawk osservati f’ pazjenti adulti bi psorjasi tal- plakka kkurati b’ 25 mg ta ’ etanercept darbtejn f’ ġimgħa.
Water for injections
Ilma għall- injezzjoni
Clear glass vial (4 ml, type I glass) with rubber stoppers, aluminium seals, and flip-off plastic caps.
Fjala ta ’ ħġieġ ċar (4 ml, ħġieġ tat- tip I) b’ tapp tal- gomma, siġill ta ’ l- aluminju, u għatu tal- plastik flip - off.
The syringes are type I glass.
Is- siringi huma tal - ħġieġ tat- tip I.
Cartons contain 4, 8 or 24 vials of Enbrel with 4, 8 or 24 pre-filled solvent syringes, 4, 8 or 24 needles, 4, 8 or 24 vial adaptors and 8, 16 or 48 alcohol swabs.
Pakett fih 4, 8 jew 24 fjala ta ’ Enbrel b’ 4, 8 jew 24 siringa mimlija minn qabel bis -
Not all pack sizes may be marketed.
78 solvent, 4, 8 jew 24 labra, 4, 8 jew 12- il adapter tal- fjala u 8, 16 jew 48 swabs ta 'l- alkoħol.
Some white
Is - soluzzjoni għandha tkun ċara u bla kulur għal isfar ċar, bla għoqod, biċċiet jew frak.
81 foam may remain in the vial – this is normal.
Xi ftit rawgħa bajda tista ’ tibqa fil- fjala – dan hu normali.