qanastek/EMEA-V3 huggingface dataset:
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 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.
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.
25 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 żjieda fil- konċentrazzjonijiet ta ’ etanercept f’ pazjenti b’ insuffiċjenza renali jew epatika akuta.
The presence of renal and hepatic impairment should not require a change in dosage.
Il- presenza ta ’ insuffiċjenza renali u epatika ma titlobx bidla fid- doża.
There is no apparent pharmacokinetic difference between males and females.
Ma hemm l- ebda evidenza ta ’ differenza farmakokinetika bejn l - irġiel u n- nisa.
Methotrexate has no effect on the pharmacokinetics of etanercept.
Methotrexate m’ għandu l- ebda effett fuq il- farmakokinetiċi ta ’ etanercept.
The effect of Enbrel on the human pharmacokinetics of methotrexate has not been investigated.
L- effett ta ’ Enbrel fuq farmakokinetiċi umani ta ’ methotrexate ma ġewx investigati.
Elderly patients
Pazjenti ta ’ età avvanzata
The impact of advanced age was studied in the population pharmacokinetic analysis of etanercept serum concentrations.
L- impatt ta ’ età avvanzata kien studjat f’ analiżi farmakokinetika ta ’ konċentrazzjoni ta ’ etanercept fis - serum f’ populazzjoni ta ’ età avvanzata.
Clearance and volume estimates in patients aged 65 to 87 years were similar to estimates in patients less than 65 years of age.
L- istimi tal- clearance u l- volum f’ pazjenti ta ’ età ta ’ bejn 65 u 87 sena kienu simili f’ pazjenti ta ’ età anqas minn 65 sena.
Paediatric patients with polyarticular juvenile idiopathic arthritis
Pazjenti bl- artrite idjopatika tal- minorenni b’ kors poliartikulari
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 b’ kors poliartikulari, 0. 4 mg/ kg Enbrel kien mogħti darbtejn f’ ġimgħa għal tliet xhur.
Serum concentration profiles were similar to those seen in adult rheumatoid arthritis patients.
Profili tal - konċentrazzjoni fis- serum kienu simili għal dawk il- pazjenti adulti li kellhom l- artrite rewmatojde.
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 żjieda ta ’ clearance meta mkejjel bl- użin) meta mqabbla ma ’ tfal akbar (ta ’ tnax- il sena) u ma ’ adulti.
Simulation of dosing suggests that while older children (10-17 years of age) will have serum levels close to those seen in adults, younger children will have appreciably lower levels.
Simulazzjoni ta ’ dożi turi li waqt tfal ta ’ età akbar (ta ’ bejn 10 u 17- il sena) ikollhom livelli ta ’ serum qrib dawk ta ’ l- adulti, tfal iżgħar ikollhom livelli iktar baxxi.
Patients with paediatric plaque psoriasis (aged 4 to 17 years) were administered 0.8 mg/ kg (up to a maximum dose of 50 mg per week) of etanercept once weekly for up to 48 weeks.
Pazjenti bi psorjasi pedjatrika tal- plakka (bejn l- 4 u s- 17- il sena) ingħataw 0. 8 mg/ kg (sa doża massima ta ’ 50 mg kull ġimgħa) ta ’ etanercept darba f’ ġimgħa sa 48 ġimgħa.
The mean serum steady state trough concentrations ranged from 1.6 to 2.1 mcg/ ml at weeks 12, 24, and 48.
Il- medja tal - konċentrazzjonijiet minimi fis- serum fl- istat fiss varjat minn 1. 6 sa 2. 1 mcg/ ml f’ ġimgħat 12, 24, u 48.
These mean concentrations in patients with paediatric plaque psoriasis were similar to the concentrations observed in patients with juvenile idiopathic arthritis (treated with 0.4 mg/ kg etanercept twice weekly, up to maximum dose of 50 mg per week).
Dawn il- konċentrazzjonijiet medji f’ pazjenti bi psorjasi pedjatrika tal- plakka kienu simili għal dawk il - konċentrazzjonijiet osservati f’ pazjenti b’ artrite idjopatika ġuvenili (ikkurati b’ 0. 4 mg/ kg ta ’ etanercept darbtejn f’ ġimgħa, sa doża massima ta ’ 50 mg kull ġimgħa).
These mean concentrations were similar to those seen in adult patients with plaque psoriasis treated with 25 mg etanercept twice weekly.
Dawn il- konċentrazzjonijiet medji kienu simili għal dawk osservati f’ pazjenti adulti bi psorjasi tal- plakka kkurati b’ 25 mg ta ’ etanercept darbtejn f’ ġimgħa.
5.3 Preclinical safety data
25 5. 3 Tagħrif ta 'qabel l- użu kliniku dwar is- sigurtà tal- mediċina
In the toxicological studies with Enbrel, no dose-limiting or target organ toxicity was evident.
Fi studji tossikoloġiċi b’ Enbrel, l- ebda limitu ta ’ doża jew tossiċità f’ xi organu magħżul ma kien evidenti.
Enbrel was considered to be non-genotoxic from a battery of in vitro and in vivo studies.
Enbrel kien ikkunsidrat li mhuwiex ġenotossiku minn batterija ta ’ studji in vitro u in vivo.
Carcinogenicity studies, and standard assessments of fertility and postnatal toxicity, were not performed with Enbrel due to the development of neutralising antibodies in rodents.
Studji tal- karċinoġeniċità u assessjar stàndard tal- fertilità u tossiċità ta ’ wara it- twelid ma kienux magħmula b’ Enbrel minħabba żvillup ta ’ antikorpi newtralizzanti f’ annimali gerriema.
Enbrel did not induce lethality or notable signs of toxicity in mice or rats following a single subcutaneous dose of 2000 mg/ kg or a single intravenous dose of 1000 mg/ kg.
Enbrel ma kienx kaġun ta ’ xi mwiet jew xi tossiċità notabbli fi ġrieden jew firien wara li ngħataw doża taħt il- ġilda ta ’ 2000mg/ kg jew doża waħda fil- vina ta ’ 1000mg/ kg.
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 rakkomandata ta ’ 25mg.
6.1 List of excipients
Lista ta 'sustanzi mhux attivi 6. 1
Mannitol Sucrose Trometamol.
Mannitol Sukkrozju Trometamol.
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
Minħabba li ma sarux studji li juru kompatibiltà dan il- prodott medicinali m’ għandux jiġi mħallat ma ’ prodotti mediċinali oħra.
Chemical and physical stability has been demonstrated for 48 hours at 2 C – 8 C.
Wara li jiġi rikostitwit, l- użu immedjat tal- prodott hu rrakkomandat Stabbilità kimika jew fiżika ntweriet għal 48 siegħa f' temperatura ta '2°C – 8°C.
From a microbiological point of view, the product should be used immediately.
Mil- lat mikrobijoloġiku, il- prodott għandu jintuża minnufih.
If not used immediately, storage times are the responsibility of the user and should normally not be longer that 6 hours at 2 C - 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.
Store in a refrigerator (2 C – 8 C).
Aħżen fi friġġ (2°C – 8°C).
Do not freeze
Tagħmlux fil- friża.
For storage conditions of the reconstituted medicinal product see section 6.3.
Għall- kundizzjonijiet ta ’ ħażna tal- prodott mediċinali rikonstitwit, ara sezzjoni 6. 3.
Clear glass vial (4 ml, type I glass) with rubber stoppers, aluminium seals, and flip-off plastic caps.
Kunjett ta ’ ħġieġ ċar (4 ml, ħġieġ tat- tip I) b’ tapp tal- gomma, siġill ta ’ l- aluminju, u għatu tal- plastik flip- off.
Enbrel is supplied with pre-filled syringes containing water for injections.
Enbrel jiġi bħala siringi mimlija għal- lest li fihom ilma għall- injezzjonijiet.
The syringes are type I glass-fitted with stainless steel needles.
Is- siringi huma tal- ħġieġ tat- tip I b’ labra ta ’ l- istainless steel.
Cartons contain 4 vials of Enbrel with 4 pre-filled solvent syringes and 8 alcohol swabs.
Pakett fih 4 fjali ta ’ Enbrel b’ 4 siringi mimlija għal- lest u 8 swabs bl- alkoħol.
6.6 Special precautions for disposal and other handling
26 6. 6 Prekawzjonijiet speċjali li għandhom jittieħdu meta jintrema u għal immaniġġar ieħor
Instructions for use and handling
Struzzjonijiet għall- użu u maniġġar u għar- rimi
Enbrel is reconstituted with 1 ml water for injections before use, and administered by subcutaneous injection.
Enbrel hu rikostitwit b’ 1 ml ilma għall- injezzjonijiet qabel jintuża, u jiġi mogħti b' injezzjoni subkutaneja.
Enbrel contains no antibacterial preservative, and therefore, solutions prepared with water for injections should be administered as soon as possible and within 6 hours following reconstitution.
Enbrel ma fihx preservattiv kontra l- batterji, u għalhekk, is- soluzzjoni ppreparata b’ ilma għall- injezzjonijiet għandha tingħata malajr kemm jista ’ jkun u f’ sitt siegħat mir- rikostituzzjoni.
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.
Some white foam may remain in the vial – this is normal.
Xi ftit rawgħa bajda tista ’ tibqa fil- kunjett – dan hu normali.
Enbrel should not be used if all the powder in the vial is not dissolved within 10 minutes.
Enbrel m' għandux jintuża jekk mhux it- trab kollu jkun inħall fi żmien 10 minuti.
Start again with another vial.
Erġa ibda mill- ġdid b’ kunjettġdid.
27 Comprehensive instructions for the preparation and administration of the reconstituted Enbrel vial are given in the package leaflet, section 7, "Instructions for preparation and giving an injection of Enbrel."
Struzzjonijiet komprensivi għall- preparazzjoni u l- għoti tal- kunjett rikostitwit ta 'Enbrel huma mogħtija fil- fuljett ta' tagħrif, sezzjoni 7, “ Struzzjonijiet għall- preparazzjoni u kif tagħti injezzjoni ta ’ Enbrel ”.
Huntercombe Lane South Taplow, Maidenhead Berkshire, SL6 0PH United Kingdom
Huntercombe Lane South Taplow, Maidenhead Berkshire, SL6 0PH Renju Unit
3 February 2000 Date of last renewal:
3 ta 'Frar 2000 Data ta' l- aħħar tiġdid:
3 February 2005
3 ta 'Frar 2005
Detailed information on this product is available on the website of the European Medicines Agency (EMEA) http: / /www. emea. europa. eu
Informazzjoni dettaljata dwar dan il- prodott tinsab fuq il- website ta ’ l- Aġenzija Ewropea dwar il - Mediċini (EMEA) http: // www. emea. europa. eu.
Enbrel 25 mg powder for solution for injection.
Enbrel 25 mg trab għal soluzzjoni għall- injezzjoni.
Powder for solution for injection.
Trab għal soluzzjoni għall- injezzjoni.
Enbrel is also indicated in the treatment of severe, active and progressive rheumatoid arthritis in adults not previously treated with methotrexate.
Enbrel huwa indikat ukoll fi trattament ta ’ artrite rewmatojde severa, attiva u progressiva fl- adulti li ma kinux ittrattati qabel b’ methotrexate.
29 Polyarticular juvenile idiopathic arthritis
Artrite idjopatika poliartikolari tal- minorenni
Treatment of active polyarticular juvenile idiopathic arthritis in children and adolescents from the age of 4 years who have had an inadequate response to, or who have proved intolerant of, methotrexate.
Trattament ta ’ artrite idjopatika poliartikolari tal- minorenni fit- tifel/ tifla u adolexxenti mill- età ta ’ 4 snin li kellhom rispons mhux adegwat għal, jew li ntwera li ma jittollerawx, methotrexate.
Psoriatic arthritis
28 Artrite psorjatika
Enbrel has been shown to improve physical function in patients with psoriatic arthritis, and to reduce the rate of progression of peripheral joint damage as measured by X-ray in patients with polyarticular symmetrical subtypes of the disease.
Intwera li Enbrel itejjeb il - funzjoni fiżika f’ pazjenti b’ artrite psorjatika, u li jnaqqas ir- rata ta ’ progressjoni ta ’ ħsara periferali tal - ġogi kif imkejla bir- raġġi X f’ pazjenti b’ sotto- tipi simmetriċi poliartikulari tal- marda.
Treatment of adults with severe active ankylosing spondylitis who have had an inadequate response to conventional therapy.
Il- kura f’ adulti li għandhom immobilità tal- vertebre kawża ta ’ infjammazzjoni severa u attiva u li kellhom rispons mhux adekwat għat- terapija konvenzjonali.
Treatment of adults with moderate to severe plaque psoriasis who failed to respond to, or who have a contraindication to, or are intolerant to other systemic therapy including cyclosporine, methotrexate or PUVA (see section 5.1).
Trattament ta ’ adulti bi psorjasi tal- plakka minn moderata sa severa li ma rreaġixxewx għal, jew li għandhom kontraindikazzjoni għal, jew li ma jittollerawx terapija sistemika oħra inkluż cyclosporine, methotrexate jew PUVA (ara Sezzjoni 5. 1).
Enbrel treatment should be initiated and supervised by specialist physicians experienced in the diagnosis and treatment of rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, plaque psoriasis or paediatric plaque psoriasis.
Il- kura b’ Enbrel għandha tinbeda taħt is- superviżjoni ta ’ tobba speċjalisti b’ esperjenza fid- dijanjosi u fil- kura ta ’ l- artrite rewmatojde, artrite idjopatika ġuvenili, l- artrite psorjatika, ankylosing spondylitis, psorjasi tal- plakka jew psorjasi pedjatrika tal- plakka.
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 li huma siguri u effettivi (ara sezzjoni 5. 1).
Psoriatic arthritis and ankylosing spondylitis
Artrite psorjatika u ankylosing spondylitis
30 Plaque psoriasis
Psorjasi tal- plakka
If re-treatment with Enbrel is indicated, the above guidance on treatment duration should be followed.
29 Jekk trattament mill- ġdid b’ Enbrel huwa indikat, il- gwida t’ hawn fuq dwar it- trattament għandha tiġi segwita.
Elderly patients ( 65 years)
Pazjenti anzjani (≥ 65 sena) L- ebda tibdil fid- doża hu meħtieġ.
0.4 mg/ kg (up to a maximum of 25 mg per dose) after reconstitution of 25 mg Enbrel in 1 ml of solvent, given twice weekly as a subcutaneous injection with an interval of 3-4 days between doses.
0. 4 mg/ kg (sa massimu ta ’ 25mg għal kull doża) wara li tħallat 25 mg Enbrel f’ 1 ml ilma għall - injezzjonijiet, mogħtija darbtejn f’ ġimgħa bħala injezzjoni taħt il- ġilda b’ intervall ta ’ 3- 4 ijiem bejn id - dożi.
No dose adjustment is required.
Indeboliment renali u epatiku L- ebda tibdil fid- doża hu meħtieġ.
31 4.4 Special warnings and precautions for use
4. 4 Avviżi speċjali u prekawzjonijiet speċjali għall- użu
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
Appropriate screening tests, i. e. tuberculin skin test and chest x-ray, should be performed in all patients (local recommendations may apply).
Testijiet adattati ta ’ l- iscreening, i. e. test tal- ġilda tuberculin u raġġi x tas- sider, għandhom jitwettqu fil- pazjenti kollha (rakkomandazzjonijiet lokali jistgħu japplikaw).
It is recommended that the conduct of these tests should be recorded in the patient ’ s alert card.
Hu rakkomandat li d- data ta ’ meta jsiru dawn testijiet għandha tkun irreġistrata fil - patient’ s alert card.
32 Worsening of hepatitis C
Aggravament ta ’ epatite Ċ
Allergic reactions
31 Reazzjonijiet Allerġiċi
The possibility exists for TNF-antagonists, including Enbrel, to affect host defences against infections and malignancies since TNF mediates inflammation and modulates cellular immune responses.
Teżisti l- possibbiltà għal antagonisti ta ’ TNF, inkluż Enbrel, li jaffettwaw id- difiża tal- bniedem kontra infjammazzjonijiet u tumuri malinni, permess li t- TNF jimmedja l- infjammazzjoni u jimmodula rispons immunitarju taċ- ċelluli.
33 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.
However, the occurrence was rare, and the follow-up period of placebo patients was shorter than for patients receiving TNF-antagonist therapy.
Madankollu, il- każijiet kienu rari, u l- perijodu ta ’ follow- up ta ’ pazjenti fuq plaċebo kien iqsar milli għal pazjenti li qed jingħataw terapija antagonista għal TNF.
Haematologic reactions
32 Reazzjonijiet Ematoloġiċi
Rare cases of pancytopenia and very rare cases of aplastic anaemia, some with fatal outcome, have been reported in patients treated with Enbrel.
Ġew irrappurtati każijiet rari ta ’ panċitopenja u każijiet rari ħafna ta ’ anemija aplastika, x’ uħud b’ konsegwanzi fatali, f’ pazjenti li ġew ikkurati b’ Enbrel.
CNS disorders
Mard tas- CNS
There have been rare reports of CNS demyelinating disorders in patients treated with Enbrel (see section 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 żjieda fl- attività tal- marda.
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.
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.
34 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.
4.5 Interaction with other medicinal products and other forms of interaction
33 4. 5 Prodotti mediċinali oħra li ma jaqblux ma ’ dan il- prodott u affarjiet oħra li jistgħu jibdlu l- effett farmaċewtiku tal- prodott
35 Non-interactions
Non- interazzjonijiet
In clinical trials, no interactions have been observed when Enbrel was administered with glucocorticoids, salicylates (except sulfasalazine), nonsteroidal anti-inflammatory drugs (NSAIDs), analgesics, or methotrexate.
Fl- istudji kliniċi, ma ġewx osservati interazzjonijiet meta Enbrel jingħata flimkien ma ’ glukokortikojdi, salicylates (ħlief sulfasalazine), mediċini kontra l- infjammazzjoni li mhumiex sterojdi (NSAIDs), analġesiċi, jew methotrexate.
See section 4.4 for vaccination advice.
Ara sezzjoni 4. 8 dwar pariri fuq it- tilqim.
4.8 Undesirable effects
34 4. 8 Effetti mhux mixtieqa
This experience includes 2 placebo-controlled studies (349 Enbrel patients and 152 placebo patients) and 2 active-controlled trials, one active-controlled trial comparing Enbrel to methotrexate (415 Enbrel patients and 217 methotrexate patients) amd another active-controlled trial comparing Enbrel (223 patients), methotrexate (228 patients) and Enbrel in combination with methotrexate (231 patients).
Din l - esperjenza tinkludi żewġ studji kkontrollati bi plaċebo (349 pazjenti li ħadu Enbrel u 152 pazjent li ħadu l- plaċebo), u żewġ studji kkontrollati attivament, studju wieħed ikkontrollat attivament li jqabbel Enbrel ma ’ methotrexate (415 pazjent fuq Enbrel u 217- il pazjent fuq methotrexate) u studju ieħor ikkontrollat attivament li qabbel Enbrel (223 pazjent), methotrexate (228 pazjent) u Enbrel flimkien ma ’ methotrexate (231 pazjent).
Additionally, Enbrel has been studied in240 psoriatic arthritis patients who participated in 2 double-blind placebo- controlled studies and an open-label extension study 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’ immobilità tal- vertebre kawża ta ’ infjammazzjoni 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.
36 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 (Enbrell 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%).
Among patients with plaque psoriasis treated in placebo-controlled trials, the frequency of serious adverse events was about 1.2% of 1,029 patients treated with Enbrel compared with 1.5% of 460 placebo-treated patients.
Fost pazjenti bi psorjasi tal- plakka trattati fi provi ikkontrollati bi plaċebo, il- frekwenza ta ’ reazzjonijiet avversi serji kienet madwar 1% minn 933 pazjent ittrattati b’ Enbrel meta mqabbla ma ’ 1. 2% minn 1, 029 pazjenti ttrattati b’ Enbrel meta mqabbla ma ’ 1. 5% ta ’ 460 pazjent ittratti bil- plaċebo.
Blood and lymphatic system disorders:
tas- sistema limfatika:
Thrombocytopenia Anaemia, leukopenia, neutropenia, pancytopenia* Aplastic anaemia*
Tromboċitopenja Anemija, lewkopenja, newtropenja, panċitopenja * Anemija aplastika *
Immune system disorders:
35 Disturbi fis- sistema immuni:
Hepatobiliary disorders:
Disturbi fil- fwied u
37 Skin and subcutaneous tissue disorders:
Disturbi fil- ġilda u fit- tessuti ta ’ taħt il- ġilda:
Pruritus Angioedema, urticaria, rash, psoriasiform rash, psoriasis (including new onset and pustular, primarily palms & soles)
Ħakk Anġjoedema, urtikarja, raxx, raxx psorjasiformi, psorjasi (li tinkludi bidu ġdid u bil- ponot, primarjament fil- keffa ta ’ l- id u fil- qiegħ tas- saqajn)
Toxic epidermal necrolysis
Vaskulite kutanea (li jinkludi vaskulite lewkoċitoklastika, Sindrome ta ’ Stevens- Johnson, eritema multiforme Nekrolisi epidermali tossika
Musculoskeletal, connective tissue and bone disorders:
Disturbi muskolu- skeltrali, tal- connective tissue u ta ’ l- għadam:
General disorders and administration site conditions:
Disturbi ġenerali u kondizzjonijiet ta ’ mnejn jingħata:
There have been reports of worsening of congestive heart failure (see section 4.4).
Kien hemm rapporti ta ’ pazjenti b’ insuffiċjenza tal- qalb konġestiva li marru għall- agħar (ara sezzjoni 4. 8).
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 - 36 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.
Twenty-three malignancies were reported in plaque psoriasis patients treated with Enbrel in double-blind and open-label studies of up to 15 months involving 1,261 Enbrel-treated patients.
Tlieta u għoxrin tumuri malinni kienu rrappurtati f’ pazjenti bi psorjasi tal - plakka ittrattati b’ Enbrel fi stħarriġ double- blind u open- label sa żmien 15- il xahar li involva 1, 261 pazjent ittrattati b’ Enbrel.
38 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.
Reports of various malignancies (including breast and lung carcinoma and lymphoma) have also been received in the postmarketing period (see section 4.4).
Saru wkoll rapporti ta ’ diversi tumuri malinni (inklużi karċinomi tas- sider u tal- pulmun u limfoma) fil - perijodu ta ’ wara t- tqegħid fis- suq (ara sezzjoni 4. 8).
Mean duration was approximately 3 to 5 days.
Iż- żmien medju ta ’ kemm damet ir- reazzjoni kienet ta ’ bejn wieħed u ieħor 3 għal 5 ijiem.
No treatment was given for the majority of injection site reactions in the Enbrel treatment groups, and the majority of patients who were given treatment received topical preparations such as corticosteroids, or oral antihistamines.
L- ebda kura ma ngħatat għall- maġġoranza tar- reazzjonijiet fis- siti ta ’ l - injezzjoni, fil- gruppi ta ’ kura b’ Enbrel, u l- maġġoranza tal- pazjenti li ngħataw il- kura użaw preperazzjonijiet topiċi bħal kortikosterojdi jew antiħistaminiċi meħuda mill- ħalq.
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’ reazzjoni 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.
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 trattati 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 żjieda ta ’ inċidenza t’ 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 - pazjenti bl- artrite rewmatojde kkurati b’ Enbrel sa 48 xhur.
These included abscess (at various sites), bacteraemia, bronchitis, bursitis, cellulitis, cholecystitis, diarrhoea, diverticulitis, endocarditis (suspected), gastroenteritis, hepatitis B, herpes zoster, leg ulcer, mouth infection, osteomyelitis, otitis, peritonitis, pneumonia, pyelonephritis, sepsis, septic arthritis, sinusitis, skin infection, skin ulcer, urinary tract infection, vasculitis, and wound infection.
Dawn kienu jinkludu qrada (f’ partijiet differenti), bakteremja, bronkite, burżite, ċellulite, koleċistite, dijarrea, divertikulite, endokardite (suspettata), gastroenterite, epatite B, herpes zoster, ulċera fis- sieq, infezzjoni fil- ħalq, osteomijelite, otitis, peritonite, pnewmonja, pajelonefrite, sepsis, artrite settika, sinużite, infezzjoni tal- ġilda, ulċera tal- ġilda, infezzjoni fil- pajpijiet ta ’ l- awrina, vaskulite, u infezzjoni fil- feriti.
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 37 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 t’ infezzjonijiet attivi jew kroniċi) flimkien ma ’ l- artite rewmatojde tagħhom (ara sezzjoni 4. 8).
The exposure-adjusted rate was 0.06 events per 100 patient-years.
Ir- rata aġġustata għall- espożizzjoni kienet ta ’ 0. 06 avvenimenti kull 100 sena ta ’ ħajja tal- pazjenti.
In postmarketing experience, approximately half of all of the case reports of opportunistic infections
Fl- esperjenza ta ’ wara l- bejgħ, madwar nofs ir - rapporti kollha ta ’ każijiet ta ’ infezzjonijiet opportunistiċi madwar id- dinja kienu infezzjonijiet fungali invażivi.
Pancytopenia and aplastic anaemia
Panċitopenja u anemija aplastika
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).
Laboratory evaluations
38 Evalwazzjoni fil- Laboratorju
Based on the results of clinical studies, normally no special laboratory evaluations are necessary in addition to careful medical management and supervision of patients.
Skond riżultati ta ’ studji kliniċi, is- soltu m’ hemmx bżonn li jsiru evalwazzjonijiet fil- laboratorju ma ’ l - imaniġġar mediku b’ attenzjoni u s- superviżjoni tal- pazjenti.
In studies when adult patients received concurrent treatment with Enbrel plus anakinra, a higher rate of serious infections compared to Enbrel alone was observed and 2% of patients (3/ 139) developed neutropenia (absolute neutrophil count < 1000 / mm3).
Fi studji fejn il- pazjenti adulti kkurati b’ Enbrel fl- istess waqt li kienet għaddejja l- kura b’ anakinra, ġie osservat li kien hemm riskju ogħla ta ’ infezzjonijiet serji meta mqabbla ma ’ l- użu ta ’ Enbrel waħdu, u 2% tal- pazjenti (3/ 139) żviluppaw newtropenja (għadd assolut tan- newtrofils < 1000 / mm3).
40 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.
Severe adverse events reported included varicella with signs and symptoms of aseptic meningitis, which resolved without sequelae (see also section 4.4), appendicitis, gastroenteritis, depression/ personality disorder, cutaneous ulcer, oesophagitis/ gastritis, group A streptococcal septic shock, type I diabetes mellitus, and soft tissue and post-operative wound infection.
Kienu rrappurtati diversi avvenimenti avversi inkużi l - ġidri r- riħ b’ sinjali u sintomi ta ’ meningite asettika li kienu imfejqa mingħajr sintomi morbużi wara l - marda (ara wkoll sezzjoni 4. 8.), appendiċite, gastroenterite, dipressjoni/ diżordni tal- personalità, ulċera fil- ġilda, esofaġite/ gastrite, xokk settiku minn streptokokku tat- tip A, diabetes mellitus tip I, u tessut artab u infezzjoni fil- ġerħa wara l- operazzjoni.
In one study in children with juvenile idiopathic arthritis aged 4 to 17 years, 43 of 69 (62%) children experienced an infection while receiving Enbrel during 3 months of the study (part 1 open-label), and the frequency and severity of infections was similar in 58 patients completing 12 months of open-label extension therapy.
Fi studju fi tfal b’ artrite idjopatika tal- minorenni ta ’ etajiet minn 4 sa 17- il sena, tlieta u erbgħin mid - 69 (62%) tfal bl- artrite kronika tal- minorenni li kienu fuq il- kura b’ Enbrel ħadu infezzjoni matul it - tliet xhur ta ’ studju (l- ewwel parti open- label), u l- frekwenza u s- severità ta ’ l- infezzjoni kienet simili f’ 58 pazjent li spiċċaw it- 12- il xahar ta ’ terapija open- label li kompliet.
The types and proportion of adverse events in juvenile idiopathic arthritis patients were similar to those seen in trials of Enbrel in adult patients with rheumatoid arthritis, and the majority were mild.
It- tipi u l- proporzzjoni ta ’ avvenimenti avversi f’ pazjenti bl- artrite idjopatika tal- minorenni hi simili għal dawk li nstabu fi studju b’ Enbrel f’ adulti bl- artrite rewmatojde, u li l- maġġoranza tagħhom kienu ħfief.
Several adverse events were reported more commonly in 69 juvenile idiopathic arthritis patients receiving 3 months of Enbrel compared to the 349 adult rheumatoid arthritis patients.
Hemm avvenimenti avversi li kienu rrappurtati aktar ta ’ spiss fil- każ ta’ 69 pazjent bl- artrite idjopatika tal- minorenni li ħadu Enbrel għal 3 xhur, imqabbla mat- 349 pazjent adulti b’ artite rewmatojde.
One rheumatoid arthritis patient mistakenly self-administered 62 mg Enbrel subcutaneously twice weekly for 3 weeks without experiencing undesirable effects.
Pazjent wieħed bl- artrite rewmatojde li bi żball ta doża lilu nniffsu taħt il- ġilda ta ’ 62 mg Enbrel darbtejn f’ ġimgħa għal tliet ġimgħat, ma kellu ebda effetti mhux mixtieqa.
41 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.
Etanercept may also modulate biologic responses controlled by additional downstream molecules (e. g., cytokines, adhesion molecules, or proteinases) that are induced or regulated by TNF.
Etanercept jista ’ wkoll jimmodula r- risponsi bijoloġiċi kkontrollati b’ żieda ta ’ molekuli “ downstream ” (eż. cytokines, molekuli ta ’ l- adeżjoni jew proteinases) li huma nduċati jew regulati mit- TNF.
ACR 20 and 50 responses were higher in patients treated with Enbrel at 3 and 6 months than in patients treated with placebo (ACR 20:
40 Ir- rispons ta ’ l- ACR 20 u 50 kien ogħla f’ pazjenti li ġew ikkurati b’ Enbrel għal 3 xhur u 6 xhur minn pazjenti kkurati bil- plaċebo (ACR 20:
Enbrel 62% and 59%, placebo 23% and 11% at 3 and 6 months respectively; ACR 50:
Enbrel 62% u 59%, plaċebo 23% u 11% f ’ 3 u f’ 6 xhur rispettivament; ACR 50:
After discontinuation of Enbrel, syptoms of arthritis generally returned within a month.
Wara li ma tkomplietx il- kura b’ Enbrel, is- sintomi ta ’ l- artrite ġeneralment reġgħu tfaċċaw fiż- żmien xahar.
Re-introduction of treatment with Enbrel after discontinuations of up to 24 months resulted in the same magnitudes of response 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.
RADIOGRAPHIC PROGRESSION:
41 PROGRESSJONI RADJOGRAFIKA:
COMPARISON OF ENBREL vs METHOTREXATE IN PATIENTS WITH RA OF < 3 YEARS
ENBREL MQABBEL MA ’ METHOTREXATE F’ PAZJENTI B ’ RATA TA ’ < 3 SNIN
43 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 t’ hawn taħt).
CLINICAL EFFICACY RESULTS AT 12 MONTHS:
42 RIŻULTATI TA ’ L- EFFIKAĊJA KLINIKA WARA 12- IL XAHAR:
Patients who did not complete 12 months in the study were considered to be non- responders. b:
Pazjenti fl- istudju li ma komplewx sat- 12- il xahar kienu kkunsidrati li huma non- responders. b:
Values for DAS are means. c:
Valuri għal Disease Activity Score (DAS) huma medji. ċ:
44 RADIOGRAPHIC PROGRESSION:
43 PROGRESSJONI RADJOGRAFIKA:
The safety and efficacy of 50 mg Enbrel (two 25 mg SC injections) administered once weekly were evaluated in a double-blind, placebo-controlled study of 420 patients with active RA.
Is- sigurtà u l- effikaċja ta ’ 50 mg Enbrel (żewġ injezzjonijiet 25 mg SC) mogħtija darba fil- ġimgħa kienu evalwati fi stħarriġ double- blind, ikkontrollat bi plaċebo ta ’ 420 pazjent b’ RA attiva.
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 tal - minorenni.
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 - 44 tieni parti, pazjenti b’ rispons kliniku fid- 90 ġurnata, kienu magħżula b’ mod każwali 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.
Responses were measured using the JRA Definition of Improvement (DOI), defined as  30% improvement in at least three of six and  30% worsening in no more than one of six JRA core set criteria, including active joint count, limitation of motion, physician and patient/ parent global assessments, functional assessment, and erythrocyte sedimentation rate (ESR).
Ir- rispons kien imkejjel bil- JRA Definizzjoni għat- Titjib (DOI), definita bħala ≥ 30% titjib f’ mill- inqas tlieta minn sitta, u ≥ 30% eħżen f’ mhux aktar minn wieħed minn sitta tal- kriterji bażiċi magħżula tal- JRA, li jinkludu total ta ’ ġogi attivi, limitazzjoni ta ’ ċaqliq, assessjar globali tat- tabib u tal- pazjent/ ġenitur, assessjar funzjonali u rata ta ’ sedimentazzjoni taċ - ċelloli l- ħomor tad- demm (ESR).
In part 2, 6 of 25 (24%) patients remaining on Enbrel experienced a disease flare compared to 20 of 26 (77%) patients receiving placebo (p=0.007).
Fit- tieni parti, 6 minn 25 (24%) tal- pazjenti li baqgħu fuq Enbrel esperjenzaw żieda qawwija fl- intensità tal- marda mqabbla ma ’ 20 minn 26 (77%) pazjenti li rċevew il- plaċebo (p=0. 007).
From the start of part 2, the median time to flare was  116 days for patients who received Enbrel and 28 days for patients who received placebo.
Mill- bidu tat- tieni parti, iż- żmien medjan għall- żieda qawwija fl- intensità tal- marda kien ta ’ ≥ 116 ġurnata għall- pazjenti li ħadu Enbrel u 28 ġurnata għall- pazjenti li ħadu l- plaċebo.
Doses of 25 mg Enbrel (based on dose-finding studies in patients with rheumatoid arthritis) or placebo were administered SC twice a week for 6 months.
Dożi ta ’ Enbrel tal- 25 mg (ibażżati fuq tagħrif minn studju fuq id- dożi mill- pazjenti b’ artrite rewmatojde) jew plaċebo kienu mogħtija SC darbtejn f’ ġimgħa għal sitt xhur.
46 RESPONSES OF PATIENTS WITH PSORIATIC ARTHRITIS IN PLACEBO-CONTROLLED TRIAL Percent of Patients
45 RISPONSI TA ’ PAZJENTI B’ ARTRITE PSORJATIKA FI STUDJU KKONTROLLAT BI PLAĊEBO% ta ’ Pazjenti Enbrela Plaċebo
47 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 50 mg once weekly dosing regimen.
46 Ma sar l- ebda studju fejn intuża r- reġimen ta ’ dożi ta ’ 50 mg darba fil- ġimgħa f’ pazjenti b’ artrite psorjatika.
The largest of these trials (n= 277) enrolled patients who were between 18 and 70 years of age and had active ankylosing spondylitis defined as visual analog scale (VAS) scores of  30 for average of duration and intensity of morning stiffness plus VAS scores of  30 for at least 2 of the following 3 parameters: patient global assessment; average of VAS values for nocturnal back pain and total back pain; average of 10 questions on the Bath Ankylosing Spondylitis Functional Index (BASFI).
L- akbar numru f ’ dawn l- istudji (n= 277) kienu pazjenti ta ’ bejn it- 18- il u s- 70 sena u li kellhom ankylosing spondylitis attiva definita bħala skala analoga viżwali (VAS) bi skor ta’ ≥ 30 għal użu ta ’ żmien medju u intensità ta ’ ebbusija ta ’ fil- għodu; flimkien ma ’ skor VAS ta ’ ≥ 30 għal mill- inqas 2 minn dawn it- 3 parametri: assessjar globali tal - pazjent; valur medju tal- VAS għal uġigħ fid- dahar matul il- lejl u uġigħ totali fid- dahar; medja ta ’ 10 domandi fuq l- Indiċi Funzjonali ta ’ l- ankylosing spondylitis fil- Banju (BASFI).
The primary measure of efficacy (ASAS 20) was a  20% improvement in at least 3 of the 4 Assessment in Ankylosing Spondylitis (ASAS) domains (patient global assessments, back pain, BASFI, and inflammation) and absence of deterioration in the remaining domain.
Il- kejl ewlieni ta ’ l- effikaċja (ASAS 20) kienet titjib ta ’ ≥ 20% f’ ta ’ mill- anqas 3 mill- 4 dominji ta ’ l - Assessjar fl- ankylosing spondylitis (ASAS) (assessjar globali tal- pazjent, uġigħ fid- dahar, BASFI, u infjammazzjoni) u nuqqas ta ’ deterjojazzjoni fid- dominju li jifdal.
ASAS 50 and 70 responses used the same criteria with a 50% improvement or a 70% improvement, respectively.
Risponsi ASAS 50 u 70 użaw l - istess kriterji b’ titjib ta ’ 50% u 70% rispettivament.
48 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
Ankylosing Spondylitis N Response ASAS 20
ASAS 20
2 weeks 3 months 6 months ASAS 50
ġimgħat
a: p < 0.001, Enbrel vs.
A: p < 0. 001, Enbrel vs.
Among patients with ankylosing spondylitis who received Enbrel, the clinical responses were apparent at the time of the first visit (2 weeks) and were maintained through 6 months of therapy.
Fost il- pazjenti b’ ankylosing spondylitis li rċevew Enbrel, ir- risponsi kliniċi kienu jidhru fl- ewwel viżta (ġimagħtejn) u komplew matul is- sitt xhur tat- terapija.
Similar results were obtained in the 2 smaller ankylosing spondylitis trials.
Riżultati simili kienu miksuba f’ żewġ studji iżgħar ta ’ pazjenti b’ ankylosing spondylitis.
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.
47 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.