Enjoy ThE simplE plEasurEs of lifE
FERRINGPHARMACEUTICALS
FOLLOW YOUR GUT FEELING
CO
R/93
9/20
14/C
H3
FERRINGPHARMACEUTICALS
2
ulcEraTivE coliTis disrupTs ThE simplE plEasurEs in lifE
• Patientswithulcerativecolitismaylivewithaconsiderablesymptomburdendespitemedicaltreatment.1,2
• Ulcerativecolitiscanhavesubstantialpsychosocialimplicationswithconsequentimpactonqualityoflife.3
• Theuseofconventionalcorticosteroidsforinflammatorydiseasesisassociatedwithgreatersideeffectsthantopical
steroids.4ASurveyinEuropeontheimpactofinflammatoryboweldiseasesonpatientslives(N=4995)showedthat2:
• 42%ofthepatientsexperiencesideeffectsfromtakingcorticosteroids.
• 49%ofthepatientsareworriedabouttheimpactofcorticosteroidsontheirlong-termhealth.
symptoms experienced at least once a day2 (n=4995)
Duringaflare Betweenflares
Bleeding 61% 28%
Abdominalcrampingpain 87% 62%
Tired,weakorwornout 96% 83%
Urgentbowelmovements 89% 66%
Diarrhoea 93% 61%
FERRINGPHARMACEUTICALS
3
ThE ThErapEuTic goals in ulcEraTivE coliTis arE:5
• inductionandmaintenanceofremissionusingwell-tolerateddrugs
• mucosalhealing
• avoidanceofsurgicalintervention
• decreasingthelikelihoodofcancer
• improvedqualityoflife.
4
FERRINGPHARMACEUTICALS
corTimEnT®mmX® is dEsignEd for local dElivEry of a poTEnT corTicosTEroid for paTiEnTs wiTh ulcEraTivE coliTis7
POTENT ANTI-INFLAMMATORY ACTIVITY
>3 times RRA* versus prednisolone and hydrocortisone10 (in vitro data) *RRA = Relative Receptor Affinity, an indirect measure of corticosteroid activity.
ORAL ADMINISTRATIONONE DOSE DAILY
PATIENT CONVENIENCE one small tablet once a day
FIRST-PASS LIVER METABOLISM
Metabolites with limited activity Low systemic exposure: about 10%9
= side effect profile similar to placebo11,12
COLONIC RELEASE SYSTEM
Targeted release for topical effect at the site of inflammation = TOPICAL ACTIVITY7
5
FERRINGPHARMACEUTICALS
corTimEnT®mmX® has an advErsE EvEnT profilE comparaBlE To placEBo11
• CORTIMENT®MMX®combineslocalcorticosteroidefficacywithlowsystemicexposure.6,7
Treatment-emergent adverse events (TEaEs)11
Safetypopulation(n=257)
Placebon=129
CORTIMENT®MMX®n=128
RelatedTEAEs 24.0% 25.8%
SeriousTEAEs 3.9% 3.1%
Potentialcorticosteroideffectsoccurredinfrequently.
Mostadverseeventswereofmild-to-moderateintensityandofanon-seriouscharacter.
most common potential corticosteroid effects at final visit 11
Safetypopulation(n=257)
Placebon=129
CORTIMENT®MMX®n=128
Moodchanges 5.4% 1.6%
Sleepchanges 3.1% 2.3%
Insomnia 1.6% 0.8%
Acne 1.6% 0.8%
Moonface 3.1% 1.6%
TablesshowsafetydatafromstudyCOREII.11COREIsafetydataaresimilar.12
6
FERRINGPHARMACEUTICALS
corTimEnT®mmX® sTudiEs usEd a rigorous dEfiniTion of rEmission and sTringEnT inclusion criTEria7,11,12
DEfINITIONOfREMISSION,UCDAI≤1WITH: INClUSIONCRITERIA
o normalstoolfrequencyo absenceofbleedingo presenceofnormalmucosawithoutfriabilityo endoscopicimprovementconfirmedbyfull
colonoscopy
o adultpatients(18-75years)o ulcerativecolitisduringatleastsixmonthso mildormoderateactivedisease(UCDAI4-10)o abnormalhistologyinatleastoneofthreebiopsiesfrom
coloniclesions
Thisrigorousdefinitionofremissionhasanimpactontheobservedremissionratesforactiveandplacebotreatmentarms.7,11,12
UCDAI:Ulcerativecolitisdiseaseactivityindex
7
FERRINGPHARMACEUTICALS
corTimEnT®mmX® 9mg shows 2,4 - 3,9 TimEs highEr rEmission raTEs comparEd To placEBo11,12
CORTIMENT®MMX®9mgshowsstatisticallysignificantresultsontheprimaryendpointversusplacebo.11,12
CLINICAL AND ENDOSCOPIC REMISSIONat week 8
0
5
10
15
20
Placebo (n=89)Re
miss
ion
%CORTIMENT®MMX® (n=109)
4.5
17.4
∆ 12.9
*Statistically significant versus placebo
p = 0.0047*
CLINICAL AND ENDOSCOPIC REMISSIONat week 8
0
5
10
15
20
Placebo (n=121)
Rem
issio
n %
CORTIMENT®MMX® (n=123)
7.4
17.9
∆ 10.4
*Statistically significant versus placebo
p = 0.0013*
clinical and Endoscopic rEmission at week 8
corE ii sTudycorE i sTudy
p=0.0143*
8
FERRINGPHARMACEUTICALS
corTimEnT®mmX® inducEs sympTom rEsoluTion afTEr 8 wEEks11,12
• CORTIMENT®MMX®9mginducessymptomresolutionafter8weeks.11,12
SYMPTOM RESOLUTION AT WEEK 8Combined rectal bleeding and stool frequency scores of 0
0
5
10
15
20
25
30
Placebo (n=89)
Sym
ptom
Res
olut
ion
%
CORTIMENT®MMX ® (n=109)
11.2
23.9
∆ 12.7p = 0.0220*
*Statistically significant versus placebo
SYMPTOM RESOLUTION AT WEEK 8Combined rectal bleeding and stool frequency scores of 0
0
5
10
15
20
25
30
Placebo (n=121)
Sym
ptom
Res
olut
ion
%
CORTIMENT®MMX ® (n=123)
16.5
28.5
∆ 11.9p = 0.0258*
*Statistically significant versus placebo
sympTom rEsoluTion at week 8Combindrectalbleedingandstoolfrequencyscoresof0
corE ii sTudycorE i sTudy
9
FERRINGPHARMACEUTICALS
• CORTIMENT®MMX®:onesmall9mgtablet,oncedaily,forupto8weeks.7
corTimEnT®mmX® offErs sympTom rEsoluTion wiTh oncE daily convEniEncE
CORTIMENT®MMX®
o Patientsgenerallypreferalowdosefrequencyandreducedpillburden.5,8,13
o Patientspreferoralintakeoverrectaluse.8
10
FERRINGPHARMACEUTICALS
corTimEnT®mmX®, Enjoy ThE simplE plEasurEs of lifE
• CORTIMENT®MMX®onesmalltablet,oncedaily,forupto8weeks
• CORTIMENT®MMX®isindicatedformild-to-moderateactiveulcerativecolitiswhere5-ASAtreatmentisnotsufficient
• CORTIMENT®MMX®isdesignedforlocaldeliveryofapotentcorticosteroid
• CORTIMENT®MMX®hasanadverseeventprofilecomparabletoplacebo
• CORTIMENT®MMX®combinescorticosteroidefficacywithlowsystemicexposure
Enjoy ThE simplE plEasurEs of lifE
1.DignassA,EliakimR,Magrofetal.SecondEuropeanevidence-basedconsensusonthediagnosisandmanagementofulcerativecolitispart1:definitionsanddiagnosis.JCrohnsColitis.2012;6:965-990.2.IMPACT2010-2011Crohn’sandUlcerativeColitisPatientlifeImpactSurvey.Presentationavailableat:http://efcca-solutions.net/european.php.lastaccessed:february2014.3.GhoshS,MitchellR.Impactofinflammatoryboweldiseaseonqualityoflife:ResultsoftheEuropeanfederationofCrohn’sandUlcerativeColitisAssociations(EfCCA)patientsurvey.JCrohnsColitis.2007;1:10-20.4.DignassA,lindsayJO,SturmAetal.SecondEuropeanevidence-basedconsensusonthediagnosisandmanagementofulcerativecolitispart2:currentmanagement.JCrohnsColitis.2012;6:991-1030.5.SiewN,KammMA.Therapeuticstrategiesforthemanagementofulcerativecolitis.InflammBowelDis.2009;15:935-950.6.farkasK,MolnarT.Novelextendedreleasebudesonideformulationfortreatmentofulcerativecolitis.ExpertOpinPharmacother.2014;15:131-137.7.ferringPharmaceuticals.Cortiment®MMX®9mgSmPC.DateofRevisionText:October2014.8.KaneSV.Systematicreview:adherenceissuesinthetreatmentofulcerativecolitis.AlimentPharmacolTher.2006;23:577-585.9.RyrfeldtA,AnderssonP,EdsbackerSetal.Pharmacokineticsandmetabolismofbudesonide,aselectiveglucocorticoid.EurJRespirDisSuppl.1982;122:86-95.10.MagerDE,MoledinaN,JuskoWJ.Relativeimmunosuppressivepotencyoftherapeuticcorticosteroidsmeasuredbywholebloodlymphocyteproliferation.JPharmSci.2003;92:1521-1525.11.TravisSP,DaneseS,Kupcinskasletal.Once-dailybudesonideMMXinactive,mild-to-moderateulcerativecolitis:resultsfromtherandomisedCOREIIstudy.Gut.2014;63:433-441.12.SandbornWJ,TravisS,Moroletal.Once-dailybudesonideMMX®extended-releasetabletsinduceremissioninpatientswithmildtomoderateulcerativecolitis:resultsfromtheCOREIstudy.Gastroenterology.2012;143:1218-26.e1.13.DignassAU,BokemeyerB,AdamekHetal.Mesalamineoncedailyismoreeffectivethantwicedailyinpatientswithquiescentulcerativecolitis.ClinGastroenterolHepatol.2009;7:762-769.
Cortiment®mmX® 9 mg,BudesonideProlongedreleasetablets. indications:CORTIMENTisindicatedinadultsforinductionofremissioninpatientswithmildtomoderateactiveulcerativecolitis(UC)where5-ASAtreatmentisnotsufficient.Dosing:Therecommendeddailydoseforinductionofremissionisone9mgtabletinthemorning,withorwithoutfood,forupto8weeks.Contraindications: Hypersensitivitytotheactivesubstance,soyaoil,peanutoilortoanyoftheexcipients.Warnings and precautions:CORTIMENTtabletsshouldbeusedwithcautioninpatientswithinfections,hypertension,diabetesmellitus,osteoporosis,pepticulcer,glaucomaorcataractsorwithafamilyhistoryofdiabetesorglaucomaorwithanyotherconditionwheretheuseofglucocorticoidsmayhaveunwantedeffects.Reducedliverfunctionmayaffecttheeliminationofglucocorticoidsincludingbudesonide,causinghighersystemicexposure.Beawareofpossiblesystemicsideeffects.Whentreatmentistobediscontinued,itmaybeusefultograduallyreducethedoseatthediscretionofthetreatingphysician.TreatmentwithCORTIMENTtabletsresultsinlowersystemicsteroidlevelsthanconventionaloralglucocorticoidtherapy.Transferfromothersteroidtherapymayresultinsymptomsrelatingtothechangeinsystemicsteroidlevels.Somepatientsmayfeelunwellduringthewithdrawalphase.Ascorticosteroidsareknowntohaveimmunologicaleffectstheco-administrationofCORTIMENTtabletsislikelytoreducetheimmuneresponsetovaccines.CORTIMENTcontainslecithin(derivedfromsoya)andlactose.interactions:NointeractionstudieshavebeenperformedBudesonideisprimarilymetabolizedbycytochromeP4503A4(CYP3A4).Inhibitorsofthisenzyme,e.g.ketoconazole,itraconazole,HIVproteaseinhibitorsandgrapefruitjuice,canthereforeincreasesystemicexposuretobudesonideseveraltimes(seesection4.4).Sincethereisnodatatosupportadosagerecommendation,thecombinationshouldbeavoided.Ifthisisnotpossible,theperiodbetweentreatmentsshouldbeaslongaspossibleandareductionofthebudesonidedosecouldalsobeconsidered.BudesonideisunlikelytoinhibitotherdrugsmetabolizedviaCYP3A4,sincebudesonidehaslowaffinitytotheenzyme.Corticosteroidinteractionsthatmaypresentasignificanthazardtoselectedpatientsarethosewithheartglycosidesanddiuretics.Fertility, pregnancy and lactation:Dataonuseofinhaledbudesonideinaverylargenumberofexposedpregnanciesindicatenoadverseeffects.Althoughtherearenodataofoutcomesofpregnanciesafteroraladministration,thebioavailabilityafteroraladministrationislow.Inanimalexperiments,athighexposures,corticosteroidsprovedtobeharmful.CORTIMENTshouldonlybeusedduringpregnancyifthepotentialbenefitjustifiesthepotentialrisktothefetus.Budesonideisexcretedinsmallamountsinbreastmilk.Duetotherapidbudesonideclearancefromtheblood,ontheoreticalgrounds,theexposuretothesucklingchildisexpectedtobelow.However,therearenodata.Adecisionmustbemadewhethertodiscontinuebreast-feedingortodiscontinue/abstainfrombudesonidetherapytakingintoaccountthebenefitofbreast-feedingforthechildandthebenefitoftherapyforthewoman. Undesirable effects:Occasionally,sideeffectstypicalofsystemicglucocorticosteroidsmayoccur.Thesesideeffectsdependonthedosage,durationoftreatment,concomitantorprevioustreatmentwithotherglucocorticosteroidsandindividualsensitivity.Steroidsclasssideeffectsincludefollowingdisorders:Skinandsubcutaneoustissue,Musculoskeletal,connectivetissueandbone,Eye,Psychiatric,Gastrointestinal,MetabolismandNutrition,Vascular,Immunesystem.overdose:Intheeventofacuteoverdosage,nospecificantidoteisavailable.Treatmentconsistsofsupportiveandsymptomatictherapy.Pharmacodynamic properties: Budesonideisreleasedintotheintestinaltractatacontrolledratethroughoutthecolon.–Clinicalefficacy:5-ASAistheStandardofCarefortreatmentofmildtomoderatedisease.ResultsofaheadtoheadcomparisonwithCORTIMENTand5-ASAarenotavailable.Therefore,theplaceinthetherapeuticwork-upremainstobeestablished.SomepatientsmaybenefitfromtreatmentinitiallywithCORTIMENT.PleasecheckwithyourlocalferringrepresentativeforlocalprescribinginformationandSmPC.Cortiment®mmX® 9 mg: Ferring Pharmaceuticals, Switzerland.
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prEscriBing informaTion
CORTIMENTisaregisteredtrademarkofferringB.V.MMXisaregisteredtrademarkofCosmoTechnologieslimited.