qanastek/EMEA-V3 huggingface dataset:
Conjunctivitis, visual acuity reduced
Konġuntivite, tnaqqis fl- akutezza tal- vista
Abdominal pain, diarrhoea, nausea, dyspepsia Gastritis, mouth ulceration, aphthous stomatitis
Ugigħ ta ’ żaqq, dijareja, nawsja, dispepsja Gastrite, ulċera fil- ħalq, stomatite aphthous
Rash (including dermatitis)
Raxx (inkluż dermatite)
Increased tendency to bruise, alopecia, dry skin
Żieda fit- tendenza għat- tbenġil, waqa ’ tax- xagħar, ġilda xotta
Musculoskeletal and connective tissue disorders
6 Disturbi muskolu- skeltrali u tal - connective tissue
Arthralgia, pain in extremity
Artralġja, uġigħ fl- estremitajiet
Lower respiratory tract infection (including bronchitis), urinary tract infection, herpes simplex, upper respiratory tract infection (including tracheitis, nasopharyngitis), rhinitis
Infezzjoni fin- naħa t’ isfel ta ’ l- apparat respiratorju (inkluż bronkite), infezzjoni fis- sistema ta ’ l - awrina, herpes simplex, infezzjoni fin- naħa ta ’ fuq ta ’ l- apparat respiratorju (inkluż trakite, nasofarinġite), rinite
Tooth infection, infected skin ulcer, onychomycosis
Infezzjoni fis- snien, ulċera tal- ġilda infettata, onikomokosi
6 Neoplasms benign, malignant and unspecified (incl. cysts and polyps)
Neoplasmi beninni, malinni u dawk mhux speċifikati (inklużi ċesti u polipi)
Basal cell carcinoma
Karċinoma taċ- ċelluli bażiċi
Hypertension, flushing Hypotension, hot flush
Pressjoni baxxa, fwawar
Fatigue, asthenia Influenza like illness
Mard simili għall- influwenza
Amenorrhea
Amenorreja
Psychiatric disorders
Disturbi psikjattriċi
Depression, anxiety
Depressjoni, ansjetà
ADRs reported in abatacept-treated patients which did not occur with an excess incidence (i. e. the difference was not > 0.2%) over placebo but were considered to be medically relevant include the following events:
ADRs li ġew irrapportati f’ pazjenti ttrattati b’ abatacept li ma ġrawx f’ inċidenza eċċessiva (jiġifieri d - differenza ma kenitx > 0. 2%) fuq plaċebo iżda li tqiesu li huma medikament rilevanti jinkludu dawn l - avvenimenti li ġejjin:
Common: herpes zoster; Uncommon: pneumonia, hypersensitivity, pyelonephritis, bronchospasm, urticaria, psoriasis, cystitis, migraine, throat tightness, dry eye; Rare: sepsis, bacteraemia.
Komuni: herpes zoster; Mhux komuni: pnewmonja, sensittività eċċessiva, pajelonefrite, spażmi fil- bronki, urtikarja, psorjażi, ċistite, emigranja, tagħfis fil- griżmejn, nixfa fl- għajnejn; Rari: sepsis, bakteremja.
Additional information
Tagħrif addizzjonali
Infections In the placebo-controlled clinical trials, infections at least possibly related to treatment were reported in 23.2% of abatacept-treated patients and 19.5% of placebo-treated patients.
Infezzjonijiet Fi provi kliniċi kkontrollati bi plaċebo, infezzjonijiet li ta ’ l- inqas jista ’ jkollhom il- possibbiltà li għandhom x’ jaqsmu mat- trattament ġew irrapportati fi 23. 2% tal- pazjenti ttrattati b’ abatacept u f’ 19. 5% tal- pazjenti ttrattati bi plaċebo.
Serious infections at least possibly related to treatment were reported in 1.8% of abatacept-treated patients and 1.0% of placebo-treated patients.
Infezzjonijiet serji li ta ’ l- inqas jista ’ jkollhom il- possibbiltà li għandhom x’ jaqsmu mat- trattament ġew irrapportati f’ 1. 8% tal- pazjenti ttrattati b’ abatacept u f’ 1. 0% tal- pazjenti ttrattati bi plaċebo.
Serious infections reported in at least one patient treated with abatacept (0.05% of patients) included the following: pneumonia; bronchitis; cellulitis; acute pyelonephritis; urinary tract infection; diverticulitis, intestinal abscess; localised infection; skin abscess; musculoskeletal infections; sepsis; empyema; hepatitis E; and tuberculosis (see section 4.4).
Infezzjonijiet serji li ġew irrapportati f’ ta ’ l- inqas pazjent wieħed ittrattat b’ abatacept (0. 05% tal - pazjenti) kienu jinkludu: pnewmonja, bronkite, ċellulite, pajelonefrite akuta; infezzjoni fis- sistema ta ’ l- awrina; divertikulite, axxess fl- intestini, infezzjoni lokalizzata; axxess fil- ġilda; infezzjonijiet muskolu- skeletali; sepsis; empjema; epatite E; u tuberkulożi (ara sezzjoni 4. 4).
Malignancies In placebo-controlled clinical trials, malignancies were reported in 27 of 1,955 abatacept-treated patients observed during 1,687 patient-years, and in 11 of 989 placebo-treated patients observed during 794 patient-years.
7 Tumuri malinni Fi provi kliniċi kkontrollati bi plaċebo, tumurin malinni ġew rappurtati f’ 27 minn 1, 955 pazjent trattati b’ abatacept osservati waqt 1, 687 sena- pazjenti, u fi 11 minn 989 pazjent trattati bi plaċebo osservati waqt 794 sena- pazjenti.
In double-blind and open-label clinical trials, malignancies were reported in 66 of 2,688 abatacept-treated patients during 4,764 patient-years.
Fi provi kliniċi double blind u open label, tumuri malinni ġew irrapportati f’ 66 minn 2, 688 pazjent trattati b’ abatacept waqt 4, 764 sena- pazjent.
This included 33 patients with non-melanoma skin cancers, 28 with solid organ cancers, and 6 with hematologic malignancies (4 with lymphomas and 2 with myelodysplastic syndromes).
Dan kien jinkludi 33 pazjent b’ kanċer tal- ġilda ta ’ bla melanoma, 28 b’ kanċer ta ’ l- organi solidi, u 6 b’ tumuri malinni ematoloġiċi (4 b’ limfomi u 2 bis - sindromu mjelodisplastiku).
The most commonly reported solid organ cancer was lung cancer (11 cases).
L- iktar kanċer ta ’ l- organi solidi li ġie rrapportat kien kanċer tal- pulmun (11- il każ).
The type and pattern of malignancies reported during the open-label period of the trials were similar to those reported for the double-blind experience.
It- tip u l- mod ta ’ tumuri malinni li ġew irraportati waqt il- perijodu ta ’ open label tal- provi kienu simili għal dawk irrapportati waqt l- esperjenza double- blind.
The number of observed malignancies was consistent with that expected in an age- and gender-matched rheumatoid arthritis population (see section 4.4).
In- numru ta ’ tumuri malinni osservati kien kostanti ma ’ dak mistenni f’ popolazzjoni ta ’ artrite tar - rewmatiżmu ta ’ l- istess età u sess (ara sezzjoni 4. 4).
Infusion-related reactions Acute infusion-related events (adverse reactions occurring within 1 hour of the start of the infusion) in Studies II, III, and IV (see section 5.1) were more common in the abatacept-treated patients than the
Reazzjonijiet li għandhom x’ jaqsmu ma ’ l- infużjoni Avvenimenti akuti relatati ma ’ l- infużjoni (reazzjonijiet avversi li seħħew fi żmien siegħa mill- bidu ta ’ l- infużjoni) fi Studji II, III u IV (ara sezzjoni 5. 1) kienu aktar komuni f’ pazjenti ttrattati b’ abatacept milli f’ pazjenti ttrattati bi plaċebo (9. 8% għal abatacept, 6. 7% għall- plaċebo).
The most frequently reported events with abatacept (1-2%) were dizziness, headache, and hypertension.
L- aktar avvenimenti frekwenti li ġew irrapportati b’ abatacept (1- 2%) kienu sturdamenti, uġigħ ta ’ ras u pressjoni għolja.
Acute infusion-related events that were reported in > 0.1% and ≤ 1% of patients treated with abatacept included cardiopulmonary symptoms such as hypotension, increased blood pressure, decreased blood pressure, and dyspnea; other symptoms included nausea, flushing, urticaria, cough, hypersensitivity, pruritus, rash, and wheezing.
Avvenimenti akuti relatati ma ’ l- infuzjoni li ġew irrapportati f ’ > 0. 1% u ≤ 1% ta ’ pazjenti ttrattati b’ abatacept inkludew sintomi kardjo- pulmonari bħal pressjoni baxxa, żieda fil- pressjoni, tnaqqis fil - pressjoni u dispneja; sintomi oħra nkludew dardir, fwawar, urtikarja, sogħla, sensittività eċċessiva, ħakk, raxx u tħarħir.
Most of these reactions were mild to moderate.
Il- biċċa l- kbira ta ’ dawn ir- reazzjonijiet kienu ħfief għal moderati.
Hypersensitivity reactions were uncommon.
Reazzjonijiet ta ’ sensittività eċċessiva ma kinux komuni.
In 2,688 abatacept-treated patients during 4,764 patient-years, there was 1 case of anaphylaxis.
F’ 2, 688 pazjent li ġew trattati b’ abatacept waqt 4, 764 sena- pazjenti, kien hemm każ wieħed ta ’ anafilassi.
Other events potentially associated with hypersensitivity to the medicinal product, such as hypotension, urticaria, and dyspnea, each occurred in less than 0.6% of abatacept-treated patients.
Avvenimenti oħra potenzjalment assoċjati ma ’ sensittività eċċessiva għall- prodott mediċinali, bħal pressjoni baxxa, urtikarja u dispneja, kull waħda seħħet f’ inqas min 0. 6% ta ’ pazjenti trattati b’ abatacept.
Discontinuation due to an acute infusion-related reaction occurred in 0.4% of patients receiving abatacept and in 0.2% of placebo-treated patients.
Twaqqif minħabba reazzjoni akuta relatata ma ’ l- infużjoni seħħ f’ 0. 4% ta ’ pazjenti li rċevew abatacept u f’ 0. 2% ta ’ pazjenti ttrattati bi plaċebo.
Adverse drug reactions in patients with chronic obstructive pulmonary disease (COPD) In Study IV, there were 37 patients with COPD treated with abatacept and 17 treated with placebo.
Reazzjonijiet avversi tal- mediċina f’ pazjenti b’ mard pulmonari ostruttiv korniku (COPD) Fi Studju IV, kien hemm 37 pazjent b’ COPD ttrattati b’ abatacept u 17 ttrattati bi plaċebo.
The COPD patients treated with abatacept developed adverse drug reactions more frequently than those treated with placebo (51.4% vs.
Il- pazjenti b’ COPD ttrattati b’ abatacept żviluppaw reazzjonijiet avversi tal- mediċina b’ iktar frekwenza milli dawk ttrattati bi plaċebo (51. 4% vs.
47.1%, respectively).
47. 1%, rispettivament).
Respiratory disorders occurred more frequently in abatacept-treated patients than in placebo-treated patients (10.8% vs.
Disturbi respiratorji seħħew bi frekwenza ikbar f’ pazjenti trattati b’ abatcept milli f’ dawk trattati bi plaċebo (10. 8% vs.
5.9%, respectively); these included COPD exacerbation, and dyspnea.
5. 9% rispettivament); dawn inkludew aggravar ta ’ COPD u dispneja.
A greater percentage of abatacept- than placebo-treated patients with COPD developed a serious adverse reaction (5.4% vs.
Perċentwal ikbar ta ’ pazjenti b’ COPD li ġew ttrattati b’ abatacept milli minn dawk ttrattati bi plaċebo żviluppaw reazzjonijiet avversi serji (5. 4% vs.
0%), including COPD exacerbation (1 of 37 patients [2.7%]) and bronchitis (1 of 37 patients [2.7%]).
0%), inkluż aggravar ta ’ COPD (1 minn 37 pazjent [2. 7%]) u bronkite (1 minn 37 pazjent [2. 7%]).
Autoantibodies Abatacept therapy did not lead to increased formation of autoantibodies, i. e., antinuclear and anti- dsDNA antibodies, compared with placebo.
Awto- antikorpi Terapija b’ abatacept ma wasslitx għal żieda fil- formazzjoni ta ’ awto- antikorpi, jiġifieri antikorpi antinukleari u antidsDNA, meta mqabbla mal- plaċebo.
Immunogenicity Antibodies directed against the abatacept molecule were assessed by ELISA assays in rheumatoid arthritis patients treated for up to 3 years with abatacept.
Immunoġeniċità Antikorpi li ġew diretti kontra l- molekula ta ’ abatacept ġew ivvalutati b’ analiżi ta ’ ELISA f’ pazjenti b’ artrite tar- rewmatiżmu ttrattati għal mhux aktar minn 3 snin b’ abatacept.
Sixty-two of 2,237 (2.8%) patients developed binding antibodies.
Tnejn u sittin minn 2, 237- il pazjent (2. 8%) żviluppaw antikorpi magħqudin.
In patients assessed for antibodies at least 56 days after discontinuation of abatacept, 15 of 203 (7.4%) developed antibodies.
F’ pazjenti vvalutati għall- antikorpi, ta ’ l- inqas 56 il - ġurnata wara t- twaqqif ta ’ abatacept, 15 minn 203 (7. 4%) żviluppaw antikorpi.
Samples with confirmed binding activity to CTLA-4 were assessed for the presence of neutralizing antibodies.
Kampjuni li ġew ikkonfermati li għandhom attività li jingħaqdu ma ’ CTLA- 4 ġew ivvalutati għall - preżenza ta ’ antikorpi newtralizzanti.
Eight of 13 evaluable patients were shown to possess neutralizing antibodies.
Tmienja minn 13- il pazjent evalwabbli wrew li kellhom antikorpi newtralizzanti.
Overall, there was no apparent correlation of antibody development to clinical response or adverse events.
8 Kollox ma ’ kollox, ma kien hemm ebda korrelazzjoni apparenti ta ’ żvilupp ta ’ antikorpi ma ’ respons kliniku jew avvenimenti avversi.
However, the number of patients that developed antibodies was too limited to make a definitive assessment.
Madankollu, in- numru ta ’ pazjenti li żviluppaw antikorpi kien limitat wisq biex issir valutazzjoni definittiva.
The potential clinical relevance of neutralizing antibody formation is not known.
Ir- rilevanza klinika potenzjali tal- formazzjoni ta ’ antikorpi newtralizzanti għadha mhux magħrufa.
Because immunogenicity analyses are product-specific, comparison of antibody rates with those from other products is not appropriate.
Minħabba li l- analiżi ta ’ l- immunoġeniċità mhumiex speċifiċi għall- prodott, it- tqabbil ta ’ rati ta ’ antikorpi ma ’ dawk minn prodotti oħra mhuwiex adegwat.
Safety information related to the pharmacological class Abatacept is the first selective co-stimulation modulator.
Tagħrif dwar is- sigurtà relatata mal- klassi farmakoloġika Abatacept huwa l- ewwel modulatur selettiv ta ’ aktar minn stimulu wieħed.
Information on the relative safety in a clinical trial versus infliximab is summarized in section 5.1.
It- tagħrif dwar is- sigurtà relattiva fi prova klinika meta mqabbla ma ’ infliximab huwa mogħti fil- qosor f’ sezzjoni 5. 1.
Doses up to 50 mg/ kg have been administered without apparent toxic effect.
Dożi sa 50 mg/ kg ingħataw mingħajr sinjali ta ’ effett tossiku.
In case of overdose, it is recommended that the patient be monitored for any signs or symptoms of adverse reactions and appropriate symptomatic treatment instituted.
F’ każ ta ’ doża eċċessiva, huwa rrakkomandat li l- pazjent jiġi mmonitorjat għal kwalunkwe sinjal jew sintomu ta ’ reazzjonijiet avversi u l- pazjent għandu jingħata trattament sintomatiku addattat.
Pharmacotherapeutic group: selective immunosuppressants, ATC code:
Kategorija farmakoterapewtika: immunosuppressanti selettivi, Kodiċi ATC:
Abatacept is a fusion protein that consists of the extracellular domain of human cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) linked to a modified Fc portion of human immunoglobulin G1 (IgG1).
Abatacept huwa proteina tal- fużjoni li tikkonsisti mid- domain ekstraċellulari ta ’ l- antiġen 4 assoċjat mal- limfoċite T ċitotossika (CTLA- 4) uman mqabbad ma ’ porzjon Fc modifikat ta ’ immunoglobulina umana G1 (IgG1) umana.
Abatacept is produced by recombinant DNA technology in Chinese hamster ovary cells.
Abatacept huwa magħmul permezz ta ’ teknoloġija ta ’ DNA rikombinanti fiċ- ċelluli ta ’ l- ovarju tal- ħamster Ċiniż.
Mechanism of action Abatacept selectively modulates a key costimulatory signal required for full activation of T lymphocytes expressing CD28.
Mekkaniżmu ta ’ azzjoni Abatacpet selettivament jimmodula sinjal ko- stimulatorju ewlieni li huwa meħtieġ għal attivazjoni totali ta ’ limfoċiti- T li juru CD28.
Full activation of T lymphocytes requires two signals provided by antigen presenting cells: recognition of a specific antigen by a T cell receptor (signal 1) and a second, costimulatory signal.
Attivazzjoni totali ta ’ limoċiti- T teħtieġ żewġ sinjali pprovduti minn ċelluli li fihom antiġen: ir- rikonoxximent ta ’ antigen speċifiku minn riċettur taċ- ċellula- T (sinjal 1) u t - tieni, sinjal li huwa ko- stimulatorju.
A major costimulatory pathway involves the binding of CD80 and CD86 molecules on the surface of antigen presenting cells to the CD28 receptor on T lymphocytes (signal 2).
Linja ko- stimulatorja maġġura tinvolvi li CD80 jaqbad ma ’ molekoli ta ’ CD86 fuq il- wiċċ ta ’ ċelluli li fihom antiġen għar- iċettur CD28 fuq il- limfoċiti T (sinjal 2).
Abatacept selectively inhibits this costimulatory pathway by specifically binding to CD80 and CD86.
Abatacept selettivament jinibixxi din il- linja ta ’ ko- stimulazzjoni billi jaqbad speċifikament ma ’ CD80 u CD86.
Studies indicate that naive T lymphocyte responses are more affected by abatacept than memory T lymphocyte responses.
Studji indikaw li responsi naïve għal limfoċiti- T huma iktar affetwati b’ abatacept milli responsi għal limfoċiti- T tal- memorja.
Studies in vitro and in animal models demonstrate that abatacept modulates T lymphocyte-dependent antibody responses and inflammation.
Studji in vitro u f’ mudelli ta ’ l- annimali juru li abatacept jimmodula responsi ta ’ antikorpi li huma dipendenti fuq limfoċiti- T u infjammazzjoni.
In vitro, abatacept attenuates human T lymphocyte activation as measured by decreased proliferation and cytokine production.
In vitro, abatacept jattenwa l- attivazzjoni ta ’ limfociti- T umani kif ġie mkejjel bi tnaqqis fil- proliferazzjoni u produzzjoni ta ’ cytokines.
Abatacept decreases antigen specific TNFα, interferon-γ, and interleukin-2 production by T lymphocytes.
Abatacept inaqqas il - produzzjoni ta ’ TNFα, interferon- γ, u interleukin- 2 li huma speċifiċi għall- antiġen, mill- limfoċiti- T.
Pharmacodynamic effects Dose-dependent reductions were observed with abatacept in serum levels of soluble interleukin-2 receptor, a marker of T lymphocyte activation; serum interleukin-6, a product of activated synovial macrophages and fibroblast-like synoviocytes in rheumatoid arthritis; rheumatoid factor, an autoantibody produced by plasma cells; and C-reactive protein, an acute phase reactant of inflammation.
Effetti farmakodinamiċi B’ abatacept, ġie osservat tnaqqis fil- livelli fis- serum ta’ riċetturi interleukin- 2 solubuli, markatur ta ’ l - attivazzjoni tal - limfoċiti- T; interleukin- 6 fis- serum, prodott ta ’ makrofaġi sinovjali attivati u sinoviċite simili għal fibroblast f’ artrite tar- rewmatiżmu; fattur ta ’ rewmatojde, awto- antikorp magħmul miċ- ċelluli tal- plasma; u proteina C- reattiva, li tirreaġġixxi fil- fażi akuta ta ’ infjammazjoni.
In addition, serum levels of matrix metalloproteinase-3, which produces cartilage destruction and tissue remodelling, were decreased.
Barra minn hekk, il- livelli fis- serum ta ’ matrix metalloproteinases- 3, li jipproduċi l- qerda tal- qarquċa u rimudellar tat- tessut, naqsu.
Reductions in serum TNFα were also observed.
Ġie osservat ukoll tnaqqis fit- TNFα fis- serum.
Clinical efficacy and safety The efficacy and safety of abatacept were assessed in randomised, double-blind, placebo-controlled clinical trials in adult patients with active rheumatoid arthritis diagnosed according to American College of Rheumatology (ACR) criteria.
Effikaċja u sigurtà klinika L- effikaċja u s- sigurtà ta ’ abatacept ġew ivvaultati fi provi kliniċi double blind ikkontrollati bi plaċebo magħmulin fuq bażi każwali f’ pazjenti adulti b’ artrite tar- rewmatiżmu attiva ddijanjostikata skond il - kriterji tal- kulleġġ Amerikan tar- rewmatoloġija (ACR).
Studies I, II, III, and V required patients to have at least 12 tender and 10 swollen joints at randomization.
Studji I, II, III u V ħtieġu pazjenti li kellhom ta ’ l- inqas 12- il ġog fi stat teneru u 10 ġogi minfuħin fuq bażi każwali.
Study IV did not require any specific number of tender or swollen joints.
Studju IV ma kellux bżonn ta ’ xi numru speċifiku ta ’ ġogi teneri jew minfuħin.
In Studies I, II, and V the efficacy and safety of abatacept compared to placebo were assessed in patients with an inadequate response to methotrexate and who continued on their stable dose of methotrexate.
9 Fi Studji I, II u V, l- effikaċja u s- sigurtà ta ’ abatacept meta mqabbla ma ’ plaċebo ġew ivvalutati f’ pazjenti b’ responsi inadegwati għal methotrexate u li komplew fuq id- doża stabbli tagħhom ta ’ methotrexate.
In addition, Study V investigated the safety and efficacy of abatacept or infliximab relative to placebo.
Barra minn hekk, studju V investiga s- sigurtà u l- effikaċja ta ’ abatacept jew infliximab meta mqabbla ma ’ plaċebo.
In Study III the efficacy and safety of abatacept were assessed in patients with an inadequate response to a TNF blocking agent, with the TNF blocking agent discontinued prior to randomization; other DMARDs were permitted.
Fi Studju III, l- effikaċja u s- sigurta ta ’ abatacept ġew ivvalutati f’ pazjenti b’ respons mhux adegwat għal sustanza li timblokka TNF, b’ din is- sustanza mwaqqfa qabel l- għażla fuq bażi każwali; DMARDs oħra ġew permessi.
Study IV primarily assessed safety in patients with active rheumatoid arthritis requiring additional intervention in spite of current therapy with non-biological and/ or biological DMARDs; all DMARDs used at enrollment were continued.
Studju IV ivvaluta primarjament is- sigurta f’ pazjenti b’ artrite tar- rewmatiżmu attiva li ħtieġu intervent addizzjonali minkejja li kienu qegħdin fuq terapija b’ DMARDs bijoloġiċi u/ jew mhux bijoloġiċi; DMARDs kollha li kienu qed jintużaw meta l- pazjenti daħlu fl- istudju baqgħu jintużaw.
Study I patients were randomized to receive abatacept 2 or 10 mg/ kg or placebo for 12 months.
Pazjenti ta ’ studju I ġew mifrudin fuq bażi każwali biex jirċievu abatacept 2 jew 10 mg/ kg jew plaċebo għal 12- il xahar.
Study II, III, and IV patients were randomized to receive a fixed dose approximating 10 mg/ kg of abatacept or placebo for 12 (Studies II and IV) or 6 months (Study III).
Pazjenti ta ’ studju II, III u IV ġew mifrudin fuq bażi każwali biex jirċievu doża fissa ta ’ bejn wieħed u ieħor 10 mg/ kg ta ’ abatacept jew plaċebo għal 12 (Studji II u IV) jew 6 xhur (Studju III).
The dose of abatacept was 500 mg for patients weighing less than 60 kg, 750 mg for patients weighing 60 to 100 kg, and 1 gram for patients weighing greater than 100 kg.
Id- doża ta ’ abatacept kienet 500 mg għall- pazjenti li kienu jiżnu inqas minn 60 kg, 750 mg għall - pazjenti li kienu jiżnu 60 sa 100 kg, u 1g għall- pazjenti li kienu jiżnu iktar minn 100 kg.
Study V patients were randomized to receive this same fixed dose of abatacept or 3 mg/ kg infliximab or placebo for 6 months.
Pazjenti ta ’ studju V ġew mifrudin fuq bażi każwali biex jirċievu din l- istess doża fissa ta ’ abatacept jew 3 mg/ kg infloximab jew plaċebo għal 6 xhur.
Study V continued for an additional 6 months with the abatacept and infliximab groups only.
Studju V kompla għal sitt xhur oħra fil- gruppi ta ’ abatacept u infliximab biss.
9 Studies I, II, III, IV, and V evaluated 339, 638, 389, 1,441, and 431 patients, respectively.
Studji I, II, III, IV u V evalwaw 339, 638, 389, 1, 441, u 431 pazjent rispettivament.
Clinical response
Respons kliniku
ACR response The percent of abatacept-treated patients achieving ACR 20, 50, and 70 responses in Study II (patients with inadequate response to methotrexate) and Study III (patients with inadequate response to TNF blocking agent) are shown in Table 3.
Respons ACR Il- perċentwali ta ’ pazjenti ttrattati b’ abatacept li ġabu ACR ta ’ 20, 50 jew 70 respons fi Studju II (pazjenti b’ respons mhux adegwat għal methotrexate) u fi Studju III (pazjenti b’ respons mhux adegwat għal sustanza li timblokka TNF) jidhru f’ Tabella 3.
In abatacept-treated patients in Studies II and III, statistically significant improvement in the ACR 20 response versus placebo was observed after administration of the first dose (day 15), and this improvement remained significant for the duration of the studies.
F’ pazjenti ttrattati b’ abatacept fi Studji II u III, titjib fir- responsi ta ’ ACR 20 li huwa statistikament sinifikattiv kontra l- plaċebo ġie osservat wara l- għoti ta ’ l- ewwel doża (jum 15), u dan it- titjib baqa ’ sinjifikanti għall- kumplament ta ’ l- istudji.
In Study II, 43% of the patients who had not achieved an ACR 20 response at 6 months developed an ACR 20 response at 12 months.
Fi Studju II, 43% tal- pazjenti li ma laħqux responsi ta ’ ACR 20 wara 6 xhur żviluppaw respons ta ’ ACR 20 fi tnax il- xahar.
Percent of Patients Inadequate Response to Inadequate Response to Methotrexate (MTX) TNF Blocking Agent Study II Study III a
Responsi ta ’ ACR fi Provi Kliniċi Kkontrollati bi Plaċebo
Abatacept Placebo Abatacepta +MTX +MTX + DMARDsb +
Perċentwal ta ’ Pazjenti Respons mhux Adegwat għal Respons mhux Adegwat għal Methotrexate (MTX) Sustanza li Timblokka TNF Studju II Studju III Abatacepta Abatacepta Plaċebo Plaċebo + DMARDsb + DMARDsb +MTX +MTX
Response Rate ACR 20
Rata ta ’ respons ACR 20
n = 133
Jum 15
23%* 14% 18%** 68%*** 40% 50%*** 73%*** 40% NAd
Xahar 6
Month 6 Month 12 ACR 70
Xahar 12 ACR 50
Month 6 Month 12 Major Clinical
Xahar 12 ACR 70
20%*** 7% 10%** 29%*** 6% NAd
18% 20% *** 10% **
Responsec *
Xahar 12 Respons Kliniku Maġġuric *
NAd
vs. plaċebo.
p < 0.05, abatacept vs. placebo. ** p < 0.01, abatacept vs. placebo. *** p < 0.001, abatacept vs. placebo. a Fixed dose approximating 10 mg/ kg (see section 4.2). b Concurrent DMARDs included one or more of the following: methotrexate, chloroquine/ hydroxychloroquine, sulfasalazine, leflunomide, azathioprine, gold, and anakinra. c Major clinical response is defined as achieving an ACR 70 response for a continuous 6-month period. d After 6 months, patients were given the opportunity to enter an open-label study.
p < 0. 01, abatacept vs. plaċebo. *** p < 0. 001, abatacept vs. plaċebo. a Doża fissa ta ’ bejn wieħed u ieħor 10 mg/ kg (ara sezzjoni 4. 2). b Użu ta ’ DMARDs fl- istess waqt inkluda wieħed jew aktar minn dawn li ġejjin: methotrexate, chloroquine/ hydroxychloroquine, sulfasalazine, leflunomide, azathioprine, deheb, u anakinra. c Respons kliniku maġġuri huwa definit bħala l- ilħuq ta ’ respons ta ’ ACR 70 għal perijodu kontinwu ta ’ 6 xhur. d Wara perjodu ta ’ sitt xhur, il- pazjenti ngħataw l- opportunità li jidħlu fi studju open label.
In the open-label extension of Studies I, II, and III durable and sustained ACR 20, 50, and 70 responses have been observed through 48, 24, and 18 months, respectively, of abatacept treatment.
Fl- estensjoni ta ’ Studji I, II u III open label, ġew osservati responsi sostenibbli u durabbli ta ’ ACR 20, 50 u 70 sa 48, 24 u 18- il xahar rispettivament, ta ’ trattament b’ abatacept.
In study I, ACR 20 responses were observed in 71% (42/ 59) of patients, ACR 50 in 41% (24/ 59), and ACR 70 in 31% (18/ 58) at 48 months.
Fi studju I, responsi ta ’ ACR 20 ġew osservati f’ 71% (42/ 59) tal- pazjenti, ACR 50 f’ 41% (24/ 59), u ACR 70 f’ 31% (18/ 58) wara 48 xahar.
In study II, ACR 20 responses were observed in 88% (291/ 332) of patients, ACR 50 in 62% (205/ 332), and ACR 70 in 38% (127/ 334) at 24 months.
Fi studju II, ġew osservati responsi ta ’ ACR 20 fi 88% (291/ 332) tal- pazjenti, ACR 50 fi 62% (205/ 332), u ACR 70 fi 38% (127/ 334) wara 24 xahar.
In study III, ACR 20 responses were observed in 70% (118/ 167) of patients, ACR 50 in 43% (73/ 168), and ACR 70 in 22% (37/ 169) at 18 months.
Fi studju III, responsi ta ’ ACR 20 ġew osservati f’ 70% (118/ 167) tal- pazjenti, ACR 50 fi 43% (73/ 168), u ACR 70 fi 22% (37/ 169) wara 18- il xahar.
10 Greater improvements were seen with abatacept than with placebo in other measures of rheumatoid arthritis disease activity not included in the ACR response criteria, such as morning stiffness.
B’ abatacept kien hemm iktar titjib meta tqabbel ma ’ plaċebo f’ miżuri oħra ta ’ l- attività tal- marda ta ’ l - artrite tar- rewmatiżmu li ma ġewx inklużi fil- kriterji ta ’ respons ta ’ l- ACR, bħal ebusija ta ’ filgħodu.
DAS28 response Disease activity was also assessed using the Disease Activity Score 28 (DAS28 ESR).
Respons DAS28 L- attività tal- marda ġiet ivvalutata wkoll bl- użu ta ’ Skor ta ’ l- Attività tal- Marda 28 (DAS 28 ESR).
There was a significant improvement of DAS in Studies II, III, and V as compared to placebo.
Kien hemm titjib sinifikanti ta ’ DAS fi Studji II, III u V meta mqabbel ma ’ plaċebo.
Study V: abatacept or infliximab versus placebo A randomized, double-blind study was conducted to assess the safety and efficacy of abatacept or infliximab versus placebo in patients with an inadequate response to methotrexate (Study V).
Studju V: abatacept jew infliximab kontra plaċebo Sar studju fuq bażi każwali, double blind biex jivvaluta s- sigurtà u l- effikaċja ta ’ abatacept jew infliximab kontra l- plaċebo f’ pazjenti li ma kellhomx respons adegwat għal methotrexate (Studju V).
The primary outcome was the mean change in disease activity in abatacept- treated patients compared to placebo-treated patients at 6 months with a subsequent double-blind assessment of safety and efficacy of abatacept and infliximab at 12 months.
Ir- riżultat primarju kien bidla medja fl- attività tal- marda f’ pazjenti ttrattati b’ abatacept meta mqabbel ma ’ dawk ttrattati bi plaċebo wara 6 xhur b’ valutazzjoni sussegwenti double blind tas- sigurtà u l - effikaċja ta ’ abatacept u infliximab wara 12- il xahar.
Greater improvement (p < 0.001) in DAS28 was observed with abatacept and with infliximab compared to placebo at six months in the placebo-controlled portion of the trial; the results between the abatacept and infliximab groups were similar.
Titjib ikbar (p < 0. 001) f’ DAS28 ġie osservat b’ abatacept u b’ infliximab meta mqabbla ma ’ plaċebo wara 6 xhur fil- porzjon ta ’ l- istudju kkontrollat minn plaċebo; ir- riżultati bejn il- gruppi ta ’ abatacept u infliximab kienu simili.
The ACR responses in Study V were consistent with the DAS28 score.
Ir- responsi ta ’ ACR fi Studju V kienu konsistenti ma ’ l- iskor ta ’ DAS28.
Further improvement was observed at 12 months with abatacept.
11 b’ abatacept.
At 6 months, the incidence of AE of infections were 48.1% (75), 52.1% (86), and 51.8% (57) and the incidence of serious AE of infections were 1.3% (2), 4.2% (7), and 2.7% (3) for abatacept, infliximab and placebo groups, respectively.
Wara 6 xhur, l- inċidenza ta ’ AE ta ’ infezzjonijiet kienu 48. 1% (75), 52. 1% (86), u 51. 8% (57) u l- inċidenza ta ’ AE serja ta ’ infezzjonijiet kienet 1. 3% (2), 4. 2% (7), u 2. 7% (3) għal abatacept, infliximab u gruppi ta ’ plaċebo rispettivament.
At 12 months, the incidence of AE of infections were 59.6% (93), 68.5% (113), and the incidence of serious AE of infections were 1.9% (3) and 8.5% (14) for abatacept and infliximab groups, respectively.
Wara 12- il xahar, l- inċidenza ta ’ AE ta ’ infezzjonijiet kienet 59. 6% (93), 68. 5% (113), u l- inċidenzata ’ AE serja ta ’ infezzjonijiet kienet 1. 9% (3) u 8. 5% (14) għall- gruppi ta ’ abatacept u infliximab, rispettivament.
Radiographic response Structural joint damage was assessed radiographically over a two-year period in Study II.
Respons radjografiku Ħsara strutturali fil- ġogi ġiet ivvalutata radjografikament fuq perijodu ta ’ sentejn fi Studju II.
The results were measured using the Genant-modified total Sharp score (TSS) and its components, the erosion score and joint space narrowing (JSN) score.
Ir - riżultati ġew imkejla bl- użu ta ’ Genant- modified total Sharp score (TSS) u l- komponenti tiegħu, l - iskor ta ’ erożjoni u l- iskor tat- tidjiq ta ’ l- ispazju bejn il- ġogi (JSN).
The baseline median TSS was 31.7 in abatacept-treated patients and 33.4 in placebo-treated patients.
Il- medja ta ’ TSS fil- linja bażi kienet ta ’ 31. 7 f’ pazjenti ttrattati b’ abatacept u 33. 4 f’ pazjenti ttrattati bi plaċebo.
Abatacept/ methotrexate reduced the rate of progression of structural damage compared to placebo/ methotrexate after 12 months of treatment as shown in Table 4.
Abatacpet/ methotrexate naqqas ir- rata ta ’ progressjoni tal- ħsara strutturali meta mqabbel ma ’ plaċebo/ methotrexate wara 12- il xahar ta ’ trattament hekk kif muri fit- Tabella 4.
The rate of progression of structural damage in year 2 was significantly lower than that in year 1 for patients randomized to abatacept (p < 0.0001).
Ir- rata ta ’ progressjoni tal- ħsara strutturali fis- sena 2 kienet ferm inqas minn dik f’ sena 1 għal pazjenti mogħtija abatacept fuq bażi każwali (p < 0. 0001).
Mean Radiographic Changes Over 12 Months in Study II Abatacept/ MTX Placebo/ MTX
Tibdil Radjografiku Medju fuq 12- il Xahar fi Studju II Abatacept/ MTX Plaċebo/ MTX Valur- Pa
Parameter Total Sharp score Erosion score JSN score a
Parametru Skor Sharp Totali Skor ta ’ l- Erożjoni Skor ta ’ JSN a
n = 391 n = 195 P-valuea 1.21 2.32 0.012 0.63 1.14 0.029 0.58 1.18 0.009
n = 391 n = 195 1. 21 2. 32 0. 012 0. 63 1. 14 0. 029 0. 58 1. 18 0. 009
Based on non-parametric analysis.
Ibbażat fuq analiżi mhux parametrika.
Physical function response Improvement in physical function was measured by the Health Assessment Questionnaire Disability Index (HAQ-DI) in Studies II, III, IV and V and the modified HAQ-DI in Study I.
Respons ta ’ funzjoni fiżika It- titjib fil- funzjoni fiżika ġie mkejjel bl- Indiċi tad- Disabilità tal- Kwestjonarju dwar il- Valutazzjoni tas- Saħħa (HAQ- DI) fi Studji II, III, IV u V u HAQ- DI modifikat fi Studju I.
The results from Studies II and III are shown in Table 5.
Ir- riżultati minn Studji II u III jidhru f’ Tabella 5.
Improvement in Physical Function in Placebo-Controlled Trials Inadequate Response to Inadequate Response Methotrexate TNF Blocking Agent Study II Study III
Titjib fil- Funżjoni Fiżika fi Provi Kkontrollati bi Plaċebo Respons mhux adegwat għal Respons mhux Adegwat għal Methotrexate Suatanza li Timblokka TNF Studju II Studju III Abatacepta Abatacepta
HAQc Disability
Indiċi ta ’ Diżabilità ta ’ HAQc
Abatacepta Placebo Abatacepta
Plaċebo Plaċebo +DMARDsb +DMARDsb +MTX +MTX
Index Baseline (Mean) Mean Improvement from Baseline
Linja Bażi (Medja) Titjib Medju mil- Linja Bażi
+DMARDsb 1.82 (n = 130)
1. 69 1. 69 1. 83 1. 82 (n = 422) (n = 212) (n = 249) (n = 130) 0. 59 *** 0. 45 ***
Month 6
Xahar 6
0.45*** (n = 249)
0. 40 0. 11 (n = 420) (n = 211) (n = 249) (n = 130) 0. 66 *** NAe NAe
Month 12 Proportion of patients with a clinically meaningful improvementd
Xahar 12 Proporzjon ta ’ pazjenti b’ titjib klinikament sinifikattivd Xahar 6
0.66*** (n = 422)
0. 37 (n = 422) (n = 212) 61% *** 47% *** 45% 23% 64% *** NAe NAe
61%*** 64%***
Xahar 12
p < 0.001, abatacept vs. placebo. a Fixed dose approximating 10 mg/ kg (see section 4.2). b Concurrent DMARDs included one or more of the following: methotrexate, chloroquine/ hydroxychloroquine, sulfasalazine, leflunomide, azathioprine, gold, and anakinra. c Health Assessment Questionnaire; 0 = best, 3 = worst; 20 questions; 8 categories: dressing and grooming, arising, eating, walking, hygiene, reach, grip, and activities. d Reduction in HAQ-DI of ≥ 0.3 units from baseline. e After 6 months, patients were given the opportunity to enter into an open-label study.
p < 0. 001, abatacept vs. plaċebo. a Doża fissa ta ’ bejn wieħed u ieħor 10 mg/ kg (ara sezzjoni 4. 2). b Użu ta ’ DMARDs fl- istess waqt inkluda wieħed jew aktar minn dawn li gejjin: methotrexate, chloroquine/ hydroxychloroquine, sulfasalazine, leflunomide, azathioprine, deheb, u anakinra. c Kwestjonarju dwar il- Valutazzjoni tas- Saħħa; 0 = l- aħjar, 3 = l- agħar; 20 mistoqsija; 8 kategoriji: tbiddil u kura personali, qawmien, ikel, mixi, iġjene, ilħuq, qbid u attivitajiet. d Tnaqqis f’ HAQ- DI ta ’ ≥ 0. 3 unità mil- linja bażi. d Wara 6 xhur, pazjenti ngħataw l- opportunità li jidħlu fi studju open label.
In Study II, among patients with clinically meaningful improvement at month 12, 88% retained the response at month 18, and 85% retained the response at month 24.
Fi Studju II, fost pazjenti b’ titjib klinikament sinifikattiv wara 12- il xahar, 88% żammew ir- respons fit- 18- il xahar, u 85% żammew ir- respons sa 24 xahar.
During the open-label period of Studies I, II, and III, the improvement in physical function has been maintained through 48, 24, and 18 months, respectively.
Waqt il- perijodu open label ta ’ Studji I, II u III, it- titjib fil- funzjoni fiżika nżamm sa 48, 24 u 18- il xahar, rispettivament.
Health-related outcomes and quality of life Health-related quality of life was assessed by the SF-36 questionnaire at 6 months in Studies I, II, and III and at 12 months in Studies I and II.
Riżultati relatati mas- saħħa u mal- kwalità tal- ħajja Il- kwalità tal- ħajja relatata mas- saħħa ġiet ivvalutata bil- kwestjonarju SF- 36 fis- 6 xahar fi Studji I, II u III u fit- 12- il xahar fi Studji I u II.
In these studies, clinically and statistically significant improvement was observed in the abatacept group as compared with the placebo group in all 8 domains of the SF-36 (4 physical domains: physical function, role physical, bodily pain, general health; and 4 mental domains: vitality, social function, role emotional, mental health), as well as the Physical Component Summary and the Mental Component Summary.
F’ dawn l- istudji, it- titjib klinikament u statistikament sinifikattiv ġie osservat fil- grupp ta ’ abatacept meta mqabbel mal- grupp tal- plaċebo fit- 8 oqsma kollha tal- SF- 36 (4 oqsma fiżiċi: funzjoni fiżika, rwol fiżiku, uġigħ fil- ġisem, saħħa b’ mod ġenerali; u 4 oqsma mentali: vitalità, funzjoni soċjali, rwol emozzjonali, saħħa mentali), kif ukoll is- Sommarju tal- Komponent Fiżiku u s- Sommarju tal- Komponent Mentali.
After multiple intravenous infusions (days 1, 15, 30, and every 4 weeks thereafter), the pharmacokinetics of abatacept in rheumatoid arthritis patients showed dose-proportional increases of Cmax and AUC over the dose range of 2 mg/ kg to 10 mg/ kg.
Wara infużjonijiet ġol- vini ripetuti (jiem 1, 15, 30 u kull 4 ġimgħat minn hemm ’ il quddiem), il - farmakokinetiċi ta ’ abatacept f’ pazjenti b’ artrite tar- rewmatiżmu wrew żidiet proporzjonati għad- doża ta ’ Cmas u AUC fuq il- medda ta ’ dożi ta ’ bejn 2 mg/ kg u 10 mg/ kg.
At 10 mg/ kg, the mean terminal half-life was 13.1 days, ranging from 8 to 25 days.
B’ 10 mg/ kg, il- medja tal- half- life terminali kienet 13. 1- il jum, fuq medda ta ’ 8 sa 25 jum.
The mean distribution volume (Vss) was 0.07 l/ kg and ranged from 0.02 to 0.13 l/ kg.
Il- volum medju tad- distribuzzjoni (Vss) kien 0. 07 l/ kg u varja bejn 0. 02 u 0. 13 l/ kg.
The systemic clearance was approximately 0.22 ml/ h/ kg.
L- eliminazzjoni sistemika kienet bejn wieħed u ieħor 0. 22 ml/ h/ kg.
Mean steady-state trough concentrations were approximately 25 μ g/ ml, and mean Cmax concentrations were approximately 290 μ g/ ml.
Il- medja ta ’ l- inqas konċentrazzjonijiet fi stat stabbli kienet bejn wieħed u ieħor 25 µg/ ml, u l- medja tal- konċentrazzjonijiet Cmas kienet bejn wieħed u ieħor 290 µg/ ml.
No systemic accumulation of abatacept occurred upon continued repeated treatment with 10 mg/ kg at monthly intervals in rheumatoid arthritis patients.
L- ebda akkumulazzjoni sistemika ta ’ abatacept ma seħħet wara trattament ripetut li tkompla b’ 10 mg/ kg f’ intervalli ta ’ kull xahar f’ pazjenti bl- artrite tar- rewmatiżmu.
Population pharmacokinetic analyses revealed that there was a trend toward higher clearance of abatacept with increasing body weight.
Analiżi farmakokinetika tal- popolazjoni żvelat li kien hemm tendenza lejn eliminazzjoni ogħla ta ’ abatacept ma ’ żieda fil- piż tal- ġisem.
Age and gender (when corrected for body weight) did not 12 affect clearance.
L- età u s- sess (meta ġew ikkoreġuti għall- piż tal- ġisem) ma 13 kellhom l- ebda effett fuq l- eliminazzjoni.
Methotrexate, NSAIDs, corticosteroids, and TNF blocking agents were not found to influence abatacept clearance.
Instab li methotrexate, NSAIDs, kortikosterojdi u sustanzi li jimblokkaw TNF ma jinflwenzawx l- eliminazzjoni ta ’ abatacept.
The pharmacokinetics of abatacept have not been studied in children and adolescents.
Il- farmakokinetici ta ’ abatacept ma ġewx studjati fit- tfal u l- adoloxxenti.
No studies were conducted to examine the effects of either renal or hepatic impairment on the pharmacokinetics of abatacept.
Ma sar ebda studju biex jeżamina l- effetti jew ta ’ indeboliment tal- fwied jew tal- kliewi fuq il- farmakokinetiċi ta ’ abatacept.
No mutagenicity or clastogenicity was observed with abatacept in a battery of in vitro studies.
L- ebda mutaġeniċità jew klastoġeniċità ma ġew osservati b’ abatacept f’ batterija ta ’ studji in vitro.
In a mouse carcinogenicity study, increases in the incidence of malignant lymphomas and mammary gland tumours (in females) occurred.
Fi studju dwar il- karċinogeniċita fil- ġrieden, kien hemm żidiet fl- inċidenza fil- limfomi malinni u f’ tumuri fil- glandoli mammarji (fin- nisa).
The increased incidence of lymphomas and mammary tumours observed in mice treated with abatacept may have been associated with decreased control of murine leukaemia virus and mouse mammary tumour virus, respectively, in the presence of long-term immunomodulation.
Iż- żieda fl- inċidenza ta ’ limfomi u tumuri mammarji osservati fil- ġrieden ttrattati b’ abatacept setgħet kienet assoċjata ma ’ tnaqqis fil- kontroll tal- vajrus tal - lewkimja tal- ġrieden u l- vajrus tat- tumuri tal- glandoli mammarji tal- ġrieden, rispettivament, fil - preżenza ta ’ immunomodulazzjoni fuq żmien twil.
In a one-year toxicity study in cynomolgus monkeys, abatacept was not associated with any significant toxicity.
Fi studju ta ’ sena fuq it- tossiċità fix- xadini tat- tip cynomolgus, abatacept ma ġiex assoċjat ma ’ xi tossiċità sinifikanti.
Reversible pharmacological effects consisted of minimal transient decreases in serum IgG and minimal to severe lymphoid depletion of germinal centres in the spleen and/ or lymph nodes.
Effetti farmakoloġiċi riversibbli kienu jikkonsistu fi tnaqqis temporanju minimu fl- IgG tas- serum, u tbattil minimu għal sever taċ- ċentri tal- ġerminazzjoni tal- limfomi fil- milsa u/ jew fil- glandoli limfatiċi.
No evidence of lymphomas or preneoplastic morphological changes was observed, despite the presence of a virus, lymphocryptovirus, which is known to cause such lesions in immunosuppressed monkeys within the time frame of this study.
L- ebda evidenza ta ’ limfomi jew bdil morfoloġiku ta ’ qabel formazzjoni ta ’ tumur ma ġiet osservata, minkejja l- preżenza ta ’ vajrus, lymphocryptovirus, li hu magħruf li jikkawża feriti f’ xadini immunosuppressati fil- limitu ta ’ żmien stipulat ta ’ dan l- istudju.
The relevance of these findings to the clinical use of ORENCIA is unknown.
Ir- relevanza ta ’ dawn is- sejbiet għall- użu kliniku ta ’ ORENCIA għandha mhux magħrufa.
In rats, abatacept had no undesirable effects on male or female fertility.
Fil- firien, abatacept ma kellux effetti mhux mixtieqa fuq il- fertilità ta ’ l- irġiel jew tan- nisa.
Embryo-foetal development studies were conducted with abatacept in mice, rats, and rabbits at doses up to 20 to 30 times a human 10 mg/ kg dose and no undesirable effects were observed in the offspring.
Saru studji fuq l- iżvilupp embrijo- fetali b’ abatacept fil- ġrieden, firien u fniek b’ dożi sa 20- 30 darba d- doża umana ta ’ 10 mg/ kg u ma ġie osservat l- ebda effett mhux mixtieq fil- frieħ.
In rats and rabbits, abatacept exposure was up to 29-fold a human 10 mg/ kg exposure based on AUC.
Fil- firien u l- fniek, l- espożizzjoni għal abatacept kienet sa 29 darba iktar l- espożizzjoni mid- doża umana ta ’ 10 mg/ kg ibbażata fuq AUC.
Abatacept was shown to cross the placenta in rats and rabbits.
Ġie muri li abatacept jaqsam il- plaċenta fil- fniek u l- firien.
In a pre- and postnatal development study with abatacept in rats, no undesirable effects were observed in pups of dams given abatacept at doses up to 45 mg/ kg, representing 3-fold a human 10 mg/ kg exposure based on AUC.
Fi studju dwar l- iżvilupp ta ’ qabel u wara t- twelid b’ abatacept fil- firien, ma dehru l- ebda effetti mhux mixtieqa fi frieħ tal- firien nisa li ngħataw abatacept f’ doża sa 45 mg/ kg, li tirrappreżenta 3- darbiet l- espożizzjoni umana ta ’ 10 mg/ kg ibbażata fuq AUC.
At a dose of 200 mg/ kg, representing 11-fold a human exposure at 10 mg/ kg based on AUC, limited changes in immune function (a 9-fold increase in the mean T-cell-dependent antibody response in female pups and inflammation of the thyroid of 1 female pup out of 10 male and 10 female pups evaluated at this dose) were observed.
F’ doża ta ’ 200 mg/ kg, li tirrappreżenta 11- il darba l- espożizzjoni umana b’ doża umana ta ’ 10 mg/ kg ibbażata fuq AUC, ġie osservat tibdil limitat fil- funzjoni ta ’ l- immunità (żieda ta ’ 9 darbiet iktar fil- medja tar- respons ta ’ antikorpi dipendenti fuq iċ- ċelluli- T fi frieħ nisa u infjammazzjoni tat- tirojde ta ’ ferħ mara (wieħed) minn 10t’ ifrieħ irġiel u 10 nisa evalwati b’ din id - doża.
Maltose Sodium dihydrogen phosphate monohydrate Sodium chloride
Maltose Sodium dihydrogen phosphate monohydrate Sodium chloride
ORENCIA should NOT be used with siliconised syringes (see section 6.6).
6. 2 Inkompatibilitajiet
3 years
3 sentejn
After reconstitution: chemical and physical in-use stability has been demonstrated for 24 hours at 2°C - 8°C.
Wara rikonstituzzjoni: intweriet stabbilità kimika u fiżika waqt l- użu għal 24 siegħa f’ temperatura ta ’ 2°C - 8°C.
From a microbiological point of view, the reconstituted solution should be diluted immediately.
Minn perspettiva mikrobijoloġika, is- soluzzjoni rikonstitwita trid tiġi dilwita minnufih.
13 After dilution: when the reconstituted solution is diluted immediately, the chemical and physical in-use stability of the diluted infusion solution has been demonstrated for 24 hours at 2°C - 8°C.
14 Wara dilwizzjoni: meta s- soluzzjoni rikonstitwita tiġi dilwita minnufih, l- istabbilità kimika u fiżika waqt l- użu tas- soluzzjoni dilwita għal infużjoni intweriet għal 24 siegħa f’ temperatura ta ’ 2°C - 8°C.
From a microbiological point of view, the product should be used immediately.
Minn perspettiva mikrobijoloġika, il- prodott għandu jintuża minnufih.
For storage conditions of the reconstituted product see section 6.3.
Għall- kundizzjonijiet ta ’ ħażna tal- prodott mediċinali rikonstitwit ara s- sezzjoni 6. 3.
250 mg powder in a vial (Type 1 glass) with a stopper (halobutyl-rubber) and flip off seal (aluminium) with a silicone-free syringe (polyethylene).
250 mg trab f’ kunjett (ħġieġ ta ’ Tip 1) b’ tapp (gomma halobutyl) u siġill li jinfetaħ b’ daqqa ta ’ saba ’ (aluminju) b’ siringa bla silikon (polyethylene).
Packs of 1, 2, or 3 vials (each 15 ml) and 1, 2, or 3 silicone-free syringes, respectively.
Pakketti ta ’ 1, 2, jew 3 kunjetti (ta ’ 15 ml il- wieħed) u 1, 2 jew 3 siringi mingħajr silikon, rispettivament.
Not all pack-sizes may be marketed.
Jista 'jkun li mhux il- pakketti tad- daqsijiet kollha jkunu għal skop kummerċjali.
Reconstitution and dilution should be performed in accordance with good practices rules, particularly with respect to asepsis.
Ir- rikonstituzzjoni u d- dilwizzjoni għandhom isiru skond regoli ta 'prattika tajba, b' mod partikolari fir - rigward ta' asepsi.
Reconstitution 1.
Rikonstituzzjoni 1.
Determine the dose and the number of ORENCIA vials needed (see section 4.2).
Stabbilixxi d- doża u n- numru ta ’ kunjetti ta ’ ORENCIA li hemm bżonn (ara sezzjoni 4. 2).
Under aseptic conditions, reconstitute each vial with 10 ml of water for injections, using the silicone free-disposable syringe provided with each vial (see section 6.2) and an 18-21 gauge needle.
Taħt kundizzjonijiet asettiċi, irrikostitwixxi kull kunjett b' 10 ml ilma għall- injezzjonijiet, billi tuża siringi bla silikon li jintremew wara l- użu pprovduti ma 'kull kunjett (ara sezzjoni 6. 2) u labra b' toqba 18- 21.
- Remove the flip-top from the vial and wipe the top with an alcohol swab.
- Neħħi t- tapp li jinfetaħ b’ daqqa ta ’ saba ’ mill- kunjett u imsaħ il- parti ta 'fuq bi swab bl- alkoħol.
- Insert the syringe needle into the vial through the centre of the rubber stopper and direct the stream
- Daħħal il- labra tas- siringa fil- kunjett minn nofs it- tapp tal- gomma u dderieġi l- ilma għall -
of water for injections to the glass wall of the vial.
injezzjonijiet lejn il- ħġieġ minn ġewwa tal- kunjett.
- Do not use the vial if the vacuum is not present.
- Tużax il- kunjett jekk ma jkunx hemm vakwu preżenti.
- Remove the syringe and needle after 10 ml of water for injections have been injected into the vial.
- Neħħi s- siringa u l- labra wara li 10 ml ta 'ilma għall- injezzjonijiet ikun ġie injettat fil- kunjett.
- To minimise foam formation in solutions of ORENCIA, the vial should be rotated with gentle
- Biex tnaqqas il- formazzjoni tar- ragħwa fis- soluzzjonijiet ta 'ORENCIA, il- kunjett għandu jiddawwar
swirling until the contents are completely dissolved.
b' tidwir ħafif sakemm il- kontenut idub għal kollox.
Avoid prolonged or vigorous agitation.
Evita li tħawwad għal ħin twil jew bis- saħħa.
- Upon complete dissolution of the powder, the vial should be vented with a needle to dissipate any
- Malli t- trab idub għal kollox, għandha tgħaddi l- arja mill- kunjett permezz ta 'labra sabiex titneħħa
foam that may be present.
ragħwa li tista 'tkun preżenti.
- After reconstitution the solution should be clear and colourless to pale yellow.
- Wara rikonstituzzjoni, is- soluzzjoni għandha tkun ċara u bla kulur għal safranija ċara.
Do not use if opaque
Tużahx jekk
particles, discolouration, or other foreign particles are present.
ikun hemm preżenti frak opaki, telf fil- kulur, jew xi partikuli barranin oħra.
Dilution 3.
Dilwizzjoni 3.