natgillin/translations-raw huggingface dataset:
Disease flare criteria were defined as a worsening of ≥ 30 % from baseline in ≥ 3 of 6 paediatric ACR core criteria, ≥ 2 active joints, and improvement of > 30 % in no more than 1 of the 6 criteria.
Merila zagona bolezni so bila opredeljena kot poslabšanje ≥ 3 od 6 osnovnih meril pediatric ACR za ≥ 30 % v primerjavi z izhodiščem, ≥ 2 aktivna sklepa in izboljšanje ne več kot 1 od 6 meril za > 30 %.
In a developmental toxicity study conducted in monkeys, there was no indication of maternal toxicity, embryotoxicity or teratogenicity.
V raziskavi razvojne toksičnosti pri opicah ni bilo znakov maternalne toksičnosti, embriotoksičnosti ali teratogenosti.
The primary efficacy endpoint in both studies was ‘time to treatment failure'.
Primarni opazovani dogodek kot merilo učinkovitosti je bil v obeh študijah ‘čas do neuspeha zdravljenja'.
Therapy continued beyond 12 weeks did not result in significantly more responses (see section 4.2).
Zdravljenje prek 12. tedna ni prineslo značilno več odzivov (glejte poglavje 4.2).
36.8 % (14 / 38) 64.9 % (24 / 37)b 43.3 % (13 / 30) 71.4 % (20 / 28)c median time to disease flare
36,8 % (14/38) 64,9 % (24/37)b 43,3 % (13/30) 71,4 % (20/28)c srednji čas do zagona bolezni
• As cases of tuberculosis have been reported in patients treated with adalimumab, your doctor will check you for signs and symptoms of tuberculosis before starting Hefiya.
• Ker so bili pri bolnikih, zdravljenih z adalimumabom, opisani primeri tuberkuloze, vas bo zdravnik pred začetkom zdravljenja z zdravilom Hefiya preiskal glede znakov in simptomov tuberkuloze.
Special populations
Posebne populacije Starejši
Other medicines and Hefiya
Druga zdravila in zdravilo Hefiya
The corresponding proportions of patients with no radiographic progression were 31.3 %, 23.7 % and 36.7 % respectively.
Ustrezni deleži bolnikov, ki niso imeli rentgenografskih znakov napredovanja, so bili 31,3 %, 23,7 % oz. 36,7 %.
Adalimumab may cross the placenta into the serum of infants born to women treated with adalimumab during pregnancy.
Adalimumab lahko prehaja skozi placento v serum dojenčkov, ki so jih rodile ženske, zdravljene z adalimumabom med nosečnostjo.
b patients meeting protocol-specified criteria for loss of response or no improvement were required to discontinue from the studies and were counted as non-responders.
b bolniki, ki izpolnjujejo merila, določena v protokolu za izgubo odziva ali brez izboljšanja, so bili izključeni iz študij in so še šteli pod bolnike brez odgovora (“nonresponders”).
Table 25 maintenance regimen patient weight low dose standard dose
Preglednica 25 vzdrževalni režim bolnikova telesna masa majhni odmerek standardni odmerek
Administration of live vaccines (e.g., BCG vaccine) to infants exposed to adalimumab in utero is not recommended for 5 months following the mother's last adalimumab injection during pregnancy.
Uporaba živih cepiv (npr. BCG cepiva) pri dojenčkih, ki so bili izpostavljeni adalimumabu in utero, ni priporočljiva še 5 mesecev po materini zadnji injekciji adalimumaba med nosečnostjo.
Consequently, these infants may be at increased risk for infection.
Posledično je lahko tveganje za okužbe pri teh dojenčkih večje.
primary analysis (ITT) placebo adalimumab time to treatment failure at or after week 2 in study UV II
primarna analiza (ITT) placebo adalimumab čas do neuspeha zdravljenja v ali po 2. tednu v študiji UV II
• The recommended injection site is the front of your thighs.
• Priporočeno mesto injiciranja je sprednji del stegen.
In Study UV II, statistically significant differences were observed for visual acuity only, but the other components were numerically in favour of adalimumab.
V študiji UV II so opazili statistično pomembne razlike samo za ostrino vida, toda tudi ostale komponente so bile glede številk v korist adalimumaba.
• Check the green indicator fills the window and has stopped moving (see Figure I).
• Preverite, da je zeleni kazalnik zapolnil okence in se je nehal premikati (glejte sliko I).
Treatment with Hefiya can be initiated in combination with corticosteroids and/or with other non-biologic immunomodulatory agents.
Zdravljenje z zdravilom Hefiya se lahko začne v kombinaciji s kortikosteroidi in/ali z drugimi nebiološkimi imunomodulatorji.
b 2-sided p value from log rank test.
b 2-stranska vrednost p testa log-rank.
6336 Langkampfen Austria
6336 Langkampfen Avstrija
The European Medicines Agency has deferred the obligation to submit the results of the studies with the reference medicinal product containing adalimumab in one or more subsets of the paediatric population in ulcerative colitis (see section 4.2 for information on paediatric use).
Evropska agencija za zdravila je začasno odložila zahtevo za predložitev rezultatov študij z referenčnim zdravilom, ki vsebuje adalimumab, za eno ali več podskupin pediatrične populacije z ulceroznim kolitisom (za podatke o uporabi pri pediatrični populaciji glejte poglavje 4.2).
Among the patients who discontinued the study prior to week 78, 11 % discontinued due to adverse events, and 5 % due to insufficient response to adalimumab treatment.
Med bolniki, ki so prekinili študijo pred 78. tednom, jih je 11 % prekinilo študijo zaradi neželenih učinkov in 5 % zaradi nezadostnega odziva na zdravljenje z adalimumabom.
Table 29 time to treatment failure in studies UV I and UV II
Preglednica 29 čas do neuspeha zdravljenja v študijah UV I in UV II
• serious infections (including blood poisoning and influenza);
• resne okužbe (vključno z zastrupitvijo krvi in gripo);
• pain in the muscles.
• bolečina v mišicah.
This risk may increase if your lung function is reduced.
Tveganje je lahko večje, če imate zmanjšano delovanje pljuč.
• If you have allergic reactions with symptoms such as chest tightness, wheezing, dizziness, swelling or rash, do not inject more Hefiya and contact your doctor immediately, since in rare cases, these reactions can be life-threatening.
• Če imate alergijske reakcije s simptomi, kot so tiščanje v prsih, piskajoče dihanje, omotica, otekanje ali izpuščaj, zdravila Hefiya ne injicirajte več in se takoj posvetujte s svojim zdravnikom, saj so v redkih primerih te reakcije lahko življenje ogrožajoče.
• Tell your doctor if you are a carrier of the hepatitis B virus (HBV), if you have active HBV infection or if you think you might be at risk of contracting HBV.
• Zdravniku povejte, če ste nosilec virusa hepatitisa B (HBV), če imate aktivno okužbo sHBV ali če mislite, da bi se lahko nalezli HBV.
Adalimumab significantly decreased the risk of treatment failure by 75% relative to placebo, as shown by the hazard ratio (HR = 0.25 [95% CI: 0.12, 0.49]).
Adalimumab je značilno zmanjšal tveganje za neuspeh zdravljenja za 75 % glede na placebo, kot prikazuje razmerje ogroženosti (HR = 0,25 [95 % IZ: 0,12, 0,49]).
The target of adalimumab is another protein called tumour necrosis factor (TNFα), which is present at increased levels in the inflammatory diseases listed above.
Tarča adalimumaba je druga beljakovina, ki se imenuje tumorje nekrotizirajoči faktor (TNFα), ki je prisoten v povečanih koncentracijah pri zgoraj navedenih vnetnih boleznih.
Fertility Preclinical data on fertility effects of adalimumab are not available.
Predkliničnih podatkov o učinkih adalimumaba na plodnost ni na voljo.
Formation of anti-adalimumab antibodies is associated with increased clearance and reduced efficacy of adalimumab.
Nastanek protiteles proti adalimumabu spremljata večji očistek in manjša učinkovitost adalimumaba.
Figure C: needle guard is not activated - the syringe is ready for use
Slika C: Ščitnik za iglo ni aktiviran - injekcijska brizga je pripravljena za uporabo
In RA study III, these improvements were maintained throughout 52 weeks.
V študiji revmatoidnega artritisa III so se ta izboljšanja ohranila 52 tednov.
Maintenance of clinical remission was evaluated in CD study III (CHARM).
Vzdrževanje klinične remisije je ocenjevala študija pri Crohnovi bolezni III (CHARM).
The patients improved following discontinuation of therapy.
Stanje bolnikov se je po prekinitvi zdravljenja izboljšalo.
If latent tuberculosis is suspected, a physician with expertise in the treatment of tuberculosis should be consulted.
Če sumite na latentno tuberkulozo, se posvetujte z zdravnikom, ki ima izkušnje z zdravljenjem tuberkuloze.
Figure D: needle guard is activated - do not use o In this configuration the needle guard is
Slika D: Ščitnik za iglo je aktiviran - ne uporabite o V tej konfiguraciji ščitnik za iglo NI
Since exposure to adalimumab can be affected by body size, adolescents with higher body weight and inadequate response may benefit from receiving the recommended adult dose of 40 mg every week.
Ker lahko velikost telesa vpliva na izpostavljenost adalimumabu, lahko mladostnikom z večjo telesno maso in nezadostnim odzivom na zdravljenje koristi jemanje priporočenega odmerka za odrasle, 40 mg vsak teden.
• new onset or worsening of psoriasis;
• izpadanje las; • pojav ali poslabšanje psoriaze;
Of the 417 subjects included in the uncontrolled long-term extension of studies UV I and UV II, 46 subjects were regarded ineligible (e.g. developed complications secondary to diabetic retinopathy, due to cataract surgery or vitrectomy) and were excluded from the primary analysis of efficacy.
Od 417 bolnikov, ki so bili vključeni v nekontrolirani dolgoročni podaljšek študij UV I in UV II, je bilo 46 bolnikov neprimernih (npr. razvili so se zapleti, sekundarno ob diabetični retinopatiji zaradi kirurškega posega sive mrene ali vitrektomije) in so bili izključeni iz primarne analize učinkovitosti.
Regarding combination with disease modifying anti-rheumatic drugs other than methotrexate see sections 4.4 and 5.1.
Za kombinirano uporabo z drugimi imunomodulirajočimi zdravili razen metotreksata glejte poglavji 4.4 in 5.1.
Of the 371 remaining patients, 276 evaluable patients reached 78 weeks of open-label adalimumab treatment.
Od preostalih 371 bolnikov je 276 ovrednotenih bolnikov zaključilo 78-tedensko odprto zdravljenje z adalimumabom.
Some of those patients were also treated with the medicines azathioprine or mercaptopurine.
Nekateri od teh bolnikov so bili zdravljeni tudi z zdraviloma azatioprinom ali merkaptopurinom.
In study UC-II, treatment with adalimumab resulted in improvements in the Inflammatory Bowel Disease Questionnaire (IBDQ) score.
V študiji UC-II je zdravljenje z adalimumabom pripeljalo do izboljšanja rezultatov Vprašalnika o vnetni bolezni črevesa (IBDQ - Inflammatory Bowel Disease Questionaire).
A similar safety profile was observed during retreatment as before withdrawal.
Varnostne značilnosti so bile po ponovnem zdravljenju podobne kot pred prenehanjem uporabe.
adalimumab n = 274 (95 % confidence interval)
adalimumab n = 274 (95 % interval zaupanja)
If such a dose is required, other adalimumab medicines should be used.
Če je potreben tak odmerek, je treba uporabiti druga zdravila z adalimumabom.
Figure B: items not included in the carton See “4.
Slika B: Predmeti, ki niso priloženi v škatli Glejte točko ''4.
discontinued corticosteroids
prenehanje s kortikosteroidi
10 6250 Kundl Austria
10 6250 Kundl Avstrija
• Do not use if the safety seal has been broken
• Ne uporabite, če je varnostni pečat zlomljen.
By attaching to TNFα, Hefiya blocks its action and reduces the inflammation in these diseases.
Z vezavo na TNFα zdravilo Hefiya zavre njegovo delovanje in zmanjša vnetni proces pri teh boleznih.
This evaluation should include a detailed medical assessment of patient history of tuberculosis or possible previous exposure to people with active tuberculosis and previous and/or current immunosuppressive therapy.
Pregled mora obsegati podrobno zdravstveno oceno bolnikove anamneze tuberkuloze ali morebitnih predhodnih stikov z ljudmi z aktivno tuberkulozo ter predhodnega in/ali trenutnega imunosupresivnega zdravljenja.
Keep Hefiya and all medicines out of the reach of children.
Zdravilo Hefiya in vsa zdravila shranjujte nedosegljivo otrokom.
The MAH shall perform the required pharmacovigilance activities and interventions detailed in the agreed RMP presented in Module 1.8.2 of the marketing authorisation and any agreed subsequent updates of the RMP.
• Načrt za obvladovanje tveganj (RMP) Imetnik dovoljenja za promet z zdravilom bo izvedel zahtevane farmakovigilančne aktivnosti in ukrepe, podrobno opisane v sprejetem RMP, predloženem v modulu 1.8.2 dovoljenja za promet z zdravilom, in vseh nadaljnjih sprejetih posodobitvah RMP.
RA study III also had a primary endpoint of changes in quality of life.
Študija revmatoidnega artritisa III je imela kot primarno končno točko tudi spremembe v kakovosti življenja.
• If you receive Hefiya during your pregnancy, your baby may have a higher risk for getting an infection.
• Če prejmete zdravilo Hefiya med nosečnostjo, obstaja večje tveganje, da bo vaš dojenček dobil okužbo.
Adalimumab concentrations in the synovial fluid from several rheumatoid arthritis patients ranged from 31-96 % of those in serum.
Koncentracije adalimumaba v sinovijski tekočini več bolnikov z revmatoidnim artritisom so bile od 31 do 96 % tistih v serumu.
Note: treatment failure at or after week 6 (study UV I), or at or after week 2 (study UV II), was counted as event.
Opomba: Neuspeh zdravljenja v ali po 6. tednu (študija UV I) ali v ali po 2. tednu (študija UV II) je bil štet kot dogodek.
Serious infections
Resne okužbe
If you have ulcerative colitis you will first be given other medicines.
Če imate ulcerozni kolitis, boste najprej dobili druga zdravila.
After doses of 0.5 mg / kg (~40 mg), clearances ranged from 11 to 15 ml / hour, the distribution volume (Vss) ranged from 5 to 6 litres and the mean terminal phase half-life was approximately two weeks.
Po odmerkih 0,5 mg/kg (~40 mg) je bil očistek od 11 do 15 ml/uro, volumen distribucije (Vss) od 5 do 6 litrov in povprečni razpolovni čas terminalne faze približno dva tedna.
Patients were permitted to be either disease-modifying, antirheumatic drug-naïve or to remain on their pre-existing rheumatologic therapy provided that therapy was stable for a minimum of 28 days.
Bolniki so bili lahko bodisi naivni za imunomodulirajoča antirevmatična zdravila bodisi so ohranili svojo prejšnjo revmatološko terapijo pod pogojem, da je bila ta terapija stabilna vsaj 28 dni.
Hospitalisation or fatal outcomes associated with infections have been reported.
Opisane so bile hospitalizacije in smrti zaradi okužb.
Of those in clinical response at week 4, 48 % had been previously exposed to other TNF-antagonists.
Od tistih, ki so imeli 4. teden klinični odziv, jih je 48 % predhodno dobilo antagoniste TNF.
In general, the adverse events in paediatric patients were similar in frequency and type to those seen in adult patients.
Na splošno so bili neželeni učinki pri pediatričnih bolnikih po pogostnosti in vrsti podobni neželenim učinkom, opaženih pri odraslih bolnikih.
Blood and the lymphatic system disorders*
Bolezni krvi in limfatičnega sistema*
Treatment with adalimumab 40 mg every week significantly reduced the risk of worsening of abscesses and draining fistulas.
Zdravljenje z adalimumabom 40 mg vsak teden statistično zmanjša tveganje za poslabšanje abscesov in fistul z izcedkom.
The potential risk with the combination of azathioprine or 6mercaptopurine and Hefiya should be carefully considered.
Potrebno je upoštevati potencialno tveganje pri sočasni uporabi azatioprina ali 6-merkaptopurina in zdravila Hefiya.
Contents of the pack and other information What Hefiya contains
Vsebina pakiranja in dodatne informacije Kaj vsebuje zdravilo Hefiya
In CD study III, at week 4, 58 % (499 / 854) of patients were in clinical response and were assessed in the primary analysis.
V študiji pri Crohnovi bolezni III je imelo 4. teden klinični odziv 58 % (499/854) bolnikov; ti so bili ocenjeni v primarni analizi.
Before initiation of therapy with Hefiya, all patients must be evaluated for both active and inactive (“latent”) tuberculosis infection.
Pred začetkom zdravljenja z zdravilom Hefiya je vse bolnike treba pregledati glede aktivne in neaktivne (latentne) tuberkulozne okužbe.
RA studies III and V had an additional primary endpoint at 52 weeks of retardation of disease progression (as detected by X-ray results).
V študijah III in V je bila dodatna primarna končna točka po 52 tednih upočasnitev napredovanja bolezni (ugotovljena z izvidi rentgenskega slikanja).
Population pharmacokinetic analyses with data from over 1,300 RA patients revealed a trend toward higher apparent clearance of adalimumab with increasing body weight.
Analize populacijske farmakokinetike s podatki za več kot 1.300 bolnikov z revmatoidnim artritisom so pokazale trend k večjemu navideznemu očistku adalimumaba z večanjem telesne teže.
Ankylosing spondylitis (AS)
Ankilozirajoči spondilitis (AS)
failure (months)
srednji čas do neuspeha (meseci)
Concurrent administration of biologic DMARDs or TNF-antagonists
Sočasna uporaba bioloških DMARD ali antagonistov TNF
• leukaemia (cancer affecting the blood and bone marrow);
• levkemija (rak, ki prizadene kri in kostni mozeg);
The apparent adalimumab plasma concentration that produces half the maximum probability of PedACR 50 response (EC50) was 3 μg/ml (95% CI: 1-6 μg/ml).
Navidezna koncentracija adalimumaba v plazmi, ki doseže polovico največje verjetnosti Ped ACR 50 odziva (EC50) je bila 3 μg/ml (95 % IZ: 1-6 μg/ml).
The efficacy and safety of adalimumab were assessed in five randomised, double-blind and wellcontrolled studies.
Učinkovitost in varnost adalimumaba so ocenili v petih randomiziranih, dvojno slepih in dobro kontroliranih študijah.
Erythema multiforme1), Stevens-Johnson syndrome1), angioedema1), cutaneous vasculitis1) lichenoid skin reaction1)
brazgotinjenje redki multiformni eritem1) sindrom Stevens-Johnson1), angioedem1), kožni vaskulitis1), lihenoidna reakcija1)
o The syringe is ready for use (see Figure C).
o Injekcijska brizga je pripravljena za uporabo (glejte sliko C).
• When needed (for example when you are travelling), Hefiya may be stored at room temperature (up to 25°C) for a maximum period of 14 days - be sure to protect it from light.
• Če je potrebno (na primer kadar potujete), lahko zdravilo Hefiya hranite pri sobni temperaturi (do 25 °C) največ 14 dni - zagotovite, da bo zaščiteno pred svetlobo.
You should not take Hefiya with medicines containing the active substances anakinra or abatacept due to increased risk of serious infection.
Zdravila Hefiya ne smete jemati z zdravili, ki vsebujejo učinkovini anakinro ali abatacept zaradi povečanega tveganja za resne okužbe.
What Hefiya is and what it is used for
Kaj je zdravilo Hefiya in za kaj ga uporabljamo
• Alcohol wipe
• alkoholni zloženec
The frequency of serious infections among adalimumab-treated subjects over 65 years of age (3.7 %) was higher than for those under 65 years of age (1.5 %).
Pri bolnikih nad 65 let, ki so prejemali adalimumab, je bila pogostost resnih okužb večja (3,7 %) kot pri tistih pod 65 let starosti (1,5 %).
Safety of the recommended adalimumab dose in the adolescent HS population is based on cross-indication safety profile of adalimumab in both adults and paediatric patients at similar or more frequent doses (see section 5.2).
Varnost priporočenega odmerka adalimumaba pri populaciji mladostnikov s HS temelji na varnostnem profilu indikacij adalimumaba pri odraslih in pediatričnih bolnikih pri podobnih ali pogostejših odmerkih (glejte poglavje 5.2).
Detailed information is available on the website of the European Medicines Agency http://www.ema.europa.eu.
Podrobne informacije so objavljene na spletni strani Evropske agencije za zdravila http://www.ema.europa.eu.
• heart problems that can cause shortness of breath or ankle swelling;
• težave s srcem, ki lahko povzročijo kratko sapo ali otekanje gležnjev;
• Hold the syringe as shown (see Figure I).
• Injekcijsko brizgo držite, kot je prikazano (glejte sliko I).
• do not use the syringe if the seals of the blister are broken, as it may not be safe for you to use.
• ne uporabljate injekcijske brizge, če so pečati pretisnega omota zlomljeni, saj uporaba za vas morda ni varna.
Symptoms may include tender nodules (lumps) and abscesses (boils) that may leak pus.
Simptomi lahko vključujejo mehke nodule (vozliče) in abscese (ognojke), iz katerih lahko izteka gnoj.
These include rare reports of pancytopenia, aplastic anaemia, central and peripheral demyelinating events and reports of lupus, lupus-related conditions and Stevens-Johnson syndrome.
To vključuje redka poročila o pancitopeniji, aplastični anemiji, centralnih in perifernih demielinizacijskih dogodkih in poročila o lupusu, z lupusom povezanimi stanji in sindromom Stevens-Johnson.
• The 1st click indicates the injection has started.
• 1. klik pomeni, da se je injiciranje začelo.
Moderate to severe heart failure (NYHA class III / IV) (see section 4.4).
Zmerno do hudo srčno popuščanje (razred III/IV po NYHA) (glejte poglavje 4.4).
In post-marketing experience from January 2003 to December 2010, predominantly in patients with rheumatoid arthritis, the reported rate of malignancies is approximately 2.7 per 1,000 patient treatment years.
V obdobju pomarketinške uporabe od januarja 2003 do decembra 2010, pretežno pri bolnikih z revmatoidnim artritisom, je bil zabeleženi delež malignomov približno 2,7 na 1000 bolnikov-let zdravljenja.
It is recommended that you use an antiseptic wash daily on the affected areas.
Priporočljivo je, da na prizadetih področjih vsak dan uporabite antiseptično čistilno tekočino.
3 defined as a closure of all fistulas that were draining at Baseline for at least 2 consecutive post-Baseline visits
3 definiran kot zaprtje vseh fistul, ki so bile prisotne ob začetku študije na vsaj 2 zaporednih obiskih po začetku
Concomitant corticosteroids may be tapered in accordance with clinical practice starting two weeks after initiating treatment with Hefiya.
Kortikosteroide, ki se jih daje sočasno, se lahko postopoma ukinja v skladu s klinično prakso, z začetkom dva tedna po začetku zdravljenja z zdravilom Hefiya.
• There may be a small amount of blood at the injection site.
• Na mestu injiciranja je lahko malo krvi.
Pharmacotherapeutic group: Immunosuppressants, Tumour Necrosis Factor alpha (TNF-α) inhibitors, ATC code: L04AB04
Farmakoterapevtska skupina: Zdravila za zaviranje imunske odzivnosti, zaviralci tumorje nekrotizirajočega faktorja alfa (TNF-α), oznaka ATC: L04AB04.
These infections have not consistently been recognised in patients taking TNF-antagonists and this has resulted in delays in appropriate treatment, sometimes resulting in fatal outcomes.
Takšne okužbe se pri uporabnikih antagonistov TNF niso pojavljale vedno, zato je v primerih njihovega nastanka prihajalo do zamud pri ustreznem zdravljenju, kar je včasih povzročilo smrt.
Drop outs due to reasons other than treatment failure were censored at the time of dropping out.
Prekinitve sodelovanja zaradi razlogov, ki niso bili posledica neuspeha zdravljenja so bile cenzurirane ob prekinitvi sodelovanja.
If you forget to give yourself an injection, you should inject the next dose of Hefiya as soon as you remember.
Če pozabite dati injekcijo, si morate naslednji odmerek zdravila Hefiya injicirati, čim se spomnite.
Sarcoidosis1), vasculitis
občasni sarkoidoza1), vaskulitis
The impact of longterm treatment with adalimumab on the development of autoimmune diseases is unknown.
Vpliv dolgoročnega zdravljenja z adalimumabom na nastanek avtoimunskih bolezni ni znan.
The criteria determining treatment failure were worsening or sustained non-improvement in ocular inflammation, partial improvement with development of sustained ocular co-morbidities or worsening of ocular co-morbidities, non-permitted use of concomitant medications, and suspension of treatment for an extended period of time.
Merila, s katerimi so določali neuspeh zdravljenja, so bili poslabšanje ali vztrajno neizboljšanje očesnega vnetja, delno izboljšanje z razvojem trajnih sočasnih očesnih bolezni ali poslabšanjem sočasnih očesnih bolezni, nedovoljena uporaba sočasnih zdravil ter prekinitev zdravljenja za daljše časovno obdobje.