j. labenz siegen, germany portoróz june 15, 2007€¦ · june 15, 2007 gastroenterology 2007....

OutcomesOutcomes of different of different Treatment Treatment ApproachesApproaches

forfor GERDGERDJ. LabenzJ. Labenz

Siegen, GermanySiegen, Germany

PortorPortoróózzJuneJune 15, 200715, 2007

GastroenterologyGastroenterology 20072007

Conclusion &RecommendationConclusion &Conclusion &RecommendationRecommendation

Relevant treatment outcomesRelevant treatment Relevant treatment outcomesoutcomes

Clinical presentationClinical presentationClinical presentation1

2

4

Medical, endoscopic andsurgical therapyMedical, endoscopic andMedical, endoscopic andsurgical therapysurgical therapy3

OverviewOverviewOverview

Clinical presentationClinical presentationClinical presentation1


EsophagealEsophagealsyndromessyndromes

ExtraesophagealExtraesophagealsyndromessyndromes

GERD GERD isis a condition a condition whichwhich developsdevelops whenwhen thethe refluxrefluxof of stomachstomach contentscontents causescauses troublesometroublesome symptomssymptoms

and / and / oror complicationscomplications

The MONTREAL Definition of GERD (Vakil et al, Am J Gastroenterol 2006)

SinusitisSinusitis

PharyngitisPharyngitis

PulmonaryPulmonary fibrosisfibrosis

Rec. Rec. otitisotitis mediamedia

ProposedProposedassociationsassociations

RefluxReflux coughcough

RefluxReflux laryngitislaryngitis

RefluxReflux asthmaasthma

Dental Dental erosionserosions

EstablishedEstablishedassociationsassociations

TypicalTypicalrefluxreflux syndromesyndrome

RefluxReflux chestchest painpainsyndromesyndrome

SymptomaticSymptomaticsyndromessyndromes

RefluxReflux esophagitisesophagitis

RefluxReflux stricturestricture

BarrettBarrett´́ss esophesoph..

AdenocarcinomaAdenocarcinoma

SyndromesSyndromes withwithesophagealesophageal injuryinjury

Relevant treatment outcomesRelevant treatment Relevant treatment outcomesoutcomes2


Goals in the management of GERD

Goals in the management Goals in the management of GERDof GERD

•• GERD is a highly prevalent GERD is a highly prevalent benignbenigndisorder.disorder.

•• Therefore, any treatment must be Therefore, any treatment must be ……

•• effective,effective,

•• safe, safe,

•• widely available, and widely available, and

•• costcost--effective.effective.

GERD: Goals of initial therapy

GERD: GERD: Goals of Goals of initialinitial therapytherapy

•• SucceedSucceed withwith initialinitial therapytherapy–– confirmconfirm thethe diagnosisdiagnosis–– achieveachieve symptomsymptom controlcontrol (as fast as (as fast as possiblepossible))–– reassurereassure thethe patientpatient as to as to thethe benignbenign and and treatabletreatable

nature of nature of refluxreflux diseasedisease–– healheal esophagitisesophagitis (as fast as (as fast as possiblepossible))

•• Do Do notnot harmharm thethe patientpatient

•• DetermineDetermine needneed forfor ongoingongoing therapytherapy

afterafter DentDent & & TalleyTalley 2003, 2003, DentDent 2004, Labenz et al 20062004, Labenz et al 2006

GERD: Goals of long-term management

GERD: GERD: Goals of Goals of longlong--termterm managementmanagement

•• MaintainMaintain symptomaticsymptomatic and and endoscopicendoscopicremissionremission

•• PreventPrevent complicationscomplications

•• Do Do notnot harmharm thethe patientpatient

•• Be Be costcost--effectiveeffective

afterafter DentDent & & TalleyTalley 2003, 2003, DentDent 2004, Labenz et al 20062004, Labenz et al 2006

Medical, endoscopic and surgical therapyMedical, endoscopic and Medical, endoscopic and surgical therapysurgical therapy3


GERD: clinical managementGERD: GERD: clinicalclinical managementmanagement

Initialmanagement

Life style Life style changeschanges

DrugsDrugs

Long-termmanagement

EndoscopicEndoscopic therapytherapy

AntirefluxAntireflux surgerysurgery

Uninvestigated GERD

Non-erosive reflux disease (NERD)

Reflux esophagitis (RE)

GERD in primary care:Three major groups

Why controlled studies ?WhyWhy controlledcontrolled studiesstudies ??

TherapeuticTherapeutic reportsreports withwith controls controls tendtend to to havehave no no enthusiasmenthusiasm,,and and reportsreports withwith enthusiasmenthusiasm

tendtend to to havehave no controlsno controls

Sackett, Chest 1989

DrugsDrugs

? x2 daily PPI + H2RA

x2 daily PPI

x1 daily PPI

x1 daily ½ PPI

Prokinetic + H2RA

Prokinetic*

Antacids + lifestyle

Antacids

Lifestyle

H2RA*OR

*no *no clearclear dosedose--responseresponse establishedestablished

HighestHighest efficacyefficacy

LowestLowest efficacyefficacy

RecommendedRecommended

ShouldShould bebeabandonedabandoned

CurrentCurrentguidelinesguidelines

Mainstream options for therapy of GERD

MainstreamMainstream optionsoptions forfor therapytherapy of of GERDGERD

afterafter DentDent et al 2002et al 2002

PPI in GERD: more than acidinhibition

PPI in GERD: PPI in GERD: moremore thanthan acidacidinhibitioninhibition

PPIPPI

BA: BA: bilebile acidsacidsDGER: DGER: DuodenoDuodeno--gastrogastro--esophagealesophageal refluxreflux

AcidAcid inhibtioninhibtion

AcidAcid & & PepsinPepsin

StomachStomachcontentscontents

GastrinGastrin

CorrosiveCorrosiveeffecteffectToxicToxic

effecteffect of BAof BA

DGERDGER

RefluxReflux volumevolume

PressurePressuregradientgradient

LES LES pressurepressure


Initialmanagement


DrugsDrugs

Esomeprazole 40 mg o.d. Esomeprazole 20 mg b.i.d.

4040

2020

00

DayDay

SensitivitySensitivity(%)(%)

Effect of PPI treatment in patients Effect of PPI treatment in patients with suspected GERDwith suspected GERD

PlaceboPlacebo

6060

8080

11 33 44 55 66 77 88 99 1010 1111 121222

100100

Johnsson et al 2004Johnsson et al 2004n=439 (330 n=439 (330 wihwih GERD)GERD)

Normal appearing esophagusNormal appearing Normal appearing esophagusesophagus

TroublesomeTroublesome refluxreflux symptomssymptomsNERDNERD

Initial treatment of NERDInitial Initial treatmenttreatment of NERDof NERD

•• AntacidsAntacids, H, H22 receptorreceptor antagonistsantagonists, and , and prokineticsprokinetics areare hardlyhardly betterbetter thanthanplaceboplacebo. .

Lauritsen 1997Lauritsen 1997

Heartburn resolutionNERD vs. ERD

HeartburnHeartburn resolutionresolutionNERD NERD vs.vs. ERDERD

9.59.5

36.736.7

00

1010

2020

3030

4040

5050

6060

7070

NERDNERDn=1,854n=1,854

7.57.5

55.555.5

ERDERDn=705n=705

PlaceboPlaceboPPIPPI

SymptomaticSymptomatic responseresponse at 4 at 4 weeksweeks%%

Dean et al, Clin Gastroenterol Hepatol 2004 Dean et al, Clin Gastroenterol Hepatol 2004

TherapeuticTherapeutic gaingain27.2%27.2%

TherapeuticTherapeutic gaingain48.0%48.0%

p<0.0001p<0.0001

SystematicSystematic reviewreview

placeboplaceboomeprazoleomeprazole 10 mg 10 mg o.do.d..omeprazoleomeprazole 20 mg 20 mg o.do.d..n=509n=509

Initial Initial treatmenttreatment of NERDof NERD

13132424

3131

49494646

6161

00

2020

4040

6060

8080

100100

SymptomSymptom--freefree SufficientSufficient symptomsymptomcontrolcontrol

SuccessSuccess at 4 at 4 weeksweeks%%

Lind et al 1997Lind et al 1997

00

2020

4040

6060

8080

100100

StudyStudy AAn=1,282n=1,282

StudyStudy BBn=693n=693

StudyStudy CCn=670n=670

OmeprazoleOmeprazole 20 mg20 mgEsomeprazoleEsomeprazole 20 mg20 mgEsomeprazoleEsomeprazole 40 mg40 mg

InititialInititial treatmenttreatment of NERD of NERD withwith a PPIa PPIDoesDoes thethe degreedegree of of acidacid inhibitioninhibition matter?matter?

Armstrong et al 2004Armstrong et al 2004

Resolution of Resolution of heartburnheartburn at at weekweek 44%%

Design: r, Design: r, dbdb, , mcmc

TheThe spectrumspectrum of NERDof NERD

NERDNERD

~ 1/3~ 1/3SI positiveSI positive

==acidacid sensitivesensitive

esophagusesophagus

~ 2/3~ 2/3SI negativeSI negative

==functionalfunctionalheartburnheartburn

Fass & Fass & TougasTougas 2002, Martinez et al 20032002, Martinez et al 2003SI: Symptom-Index

acidacidrelatedrelated

PredictionPrediction of of thetheresponseresponse to PPI to PPI

(60(60--70%)70%)

~ 50% ~ 50% no no acidacid refluxreflux

~ 50%~ 50%acidacid refluxreflux pH pH metrymetry

NERD: NERD: OnOn--demanddemand vsvs continuouscontinuousPPI PPI –– TheThe COMMAND COMMAND studystudy

TsaiTsai et al 2004et al 2004

Patients satisfied after 6 months, %

8893

0

20

40

60

80

100

Esomeprazole 20 mg on demand

n=311

Lansoprazole 15 mgdaily

n=311

p=0.02

Drug Drug consumptionconsumption „„onon--demanddemand““ vs. vs. dailydaily::--72%72%

Reflux esophagitisReflux Reflux esophagitisesophagitis


Initialmanagement


DrugsDrugs

00

2020

4040

6060

Patients free from heartburnPatients free from heartburn%%

00 11––22 33––44 66––88Weeks of treatmentWeeks of treatment

HH22--receptorreceptorantagonistsantagonists

MetaMeta--analysis analysis n=2,198n=2,198

PPIsPPIs

p<0.0001p<0.0001

8800

Speed of symptom resolution in patients with reflux esophagitisSpeed of symptom resolution in Speed of symptom resolution in patients with reflux patients with reflux esophagitisesophagitis

Chiba et al 1997Chiba et al 1997

p<0.0005

00

2020

4040

6060

8080

Esophagitis cases healedEsophagitis cases healed, %, %

00 22 44 66 88 1010 1212Time (weeks)Time (weeks)

PPIsPPIs

HH22--receptorreceptorantagonistsantagonists

PlaceboPlacebo

100100

MetaMeta--analysisanalysis: n=7,635: n=7,635

83.683.6

51.951.9

28.228.2

Speed of healing of reflux esophagitis

Speed of healing Speed of healing of reflux esophagitisof reflux esophagitis

Chiba et al 1997Chiba et al 1997

00

2020

4040

6060

8080

100100

Richter 2001Richter 2001n=2425n=2425

CastellCastell 20022002n=5241n=5241

Labenz 2005Labenz 2005n=3151n=3151

OmeprazoleOmeprazole 20 mg20 mgLansoprazoleLansoprazole 30 mg30 mgPantoprazolePantoprazole 40 mg40 mg

Healing of reflux esophagitisEsomeprazole vs. other PPIsHealing of reflux Healing of reflux esophagitisesophagitisEsomeprazoleEsomeprazole vs. other vs. other PPIsPPIs

OMEOME LANLAN PANPAN

EsophagitisEsophagitis healedhealed afterafter 4 4 weeksweeks%%

69697575 7474

EsomeprazoleEsomeprazole 40 mg40 mg

*p<0.0001*p<0.0001Log rankLog rank

82*82*79*79* 81*81*

00

2020

4040

6060

8080

100100

Richter 2001Richter 2001n=2425n=2425

CastellCastell 20022002n=5241n=5241

Labenz 2005Labenz 2005n=3151n=3151

OmeprazoleOmeprazole 20 mg20 mgLansoprazoleLansoprazole 30 mg30 mgPantoprazolePantoprazole 40 mg40 mg

Healing of reflux esophagitisEsomeprazole vs. other PPIsHealing of reflux Healing of reflux esophagitisesophagitisEsomeprazoleEsomeprazole vs. other vs. other PPIsPPIs

OMEOME LANLAN PANPAN

EsophagitisEsophagitis healedhealed afterafter 8 8 weeksweeks%%

84848989 9292

EsomeprazoleEsomeprazole 40 mg40 mg

*p<0.0001*p<0.0001Log rankLog rank

94*94* 93*93* 96*96*

Long-term treatment of erosivereflux esophagitis

LongLong--termterm treatmenttreatment of of erosiveerosiverefluxreflux esophagitisesophagitis

OmeprazoleOmeprazole

00

1010

2020

3030

4040

5050

6060

7070

8080

9090

100100

00 11 22 33 44 55 66 77 88 99 1010 1111 1212 1313 1414 1515 1616 1717 1818 1919 2020 2121 2222 2424 monthsmonths

PatientsPatients in in remissionremission

HH22--blockerblocker

PlaceboPlacebo

OmeOme 20 mg/d20 mg/d

CimeCime 16001600––3200 mg/d3200 mg/d

Ran 2 x 150 mg/dRan 2 x 150 mg/d

Ran 2 x 150 mg/dRan 2 x 150 mg/d

FamoFamo 2 x 40 mg/d2 x 40 mg/d

PlaceboPlacebo

2323

%%

2929

5454

79798888

2929

5757

9393 9494

00

2020

4040

6060

8080

100100

PlaceboPlacebo94 7794 77

10 mg10 mg91 7791 77

20 mg20 mg98 8298 82

40 mg40 mg92 8292 82

VakilVakil 20012001JohnssonJohnsson 20012001

EsoEso vs. Placebo:vs. Placebo:p<0.001p<0.001

Maintaining remission of erosiveesophagitis: effect of PPI titrationMaintaining remission of erosive

esophagitis: effect of PPI titrationRemission at 6 Remission at 6 monthsmonths%%

EsomeprazoleEsomeprazole

nsns

JohnssonJohnsson et al 2001, et al 2001, VakilVakil et al 2001et al 2001

n=n=

00

5050

100100

150150

200200

250250

300300

EsomeprazoleEsomeprazole 20 mg20 mgn=1,398n=1,398

PantoprazolePantoprazole 20 mg20 mgn=1,415n=1,415

1.5%1.5%

1.3%1.3%OthersOthers

AdverseAdverse eventevent

5.6%5.6%

12.8%12.8% Lack of Lack of efficacyefficacy

Labenz et al 2005Labenz et al 2005

EXPO study maintenance phase:Reasons for discontinuation

EXPO study maintenance phase:EXPO study maintenance phase:Reasons for discontinuationReasons for discontinuation

NumberNumber of of patientspatients, n, n

Long-term prevention of erosive orulcerative reflux disease

LongLong--termterm preventionprevention of of erosiveerosive ororulcerativeulcerative refluxreflux diseasedisease

6363

23231111

00

2020

4040

6060

8080

100100

PlaceboPlacebo RabeprazoleRabeprazole10 mg10 mg

RabeprazoleRabeprazole20 mg20 mg

RelapseRelapse withinwithin 5 y, %5 y, %

PlaceboPlacebo--controlledcontrolled RCT (n=497) RCT (n=497) CaosCaos et al 2005et al 2005

RabeprazoleRabeprazole vs. Placebo: p<0.001vs. Placebo: p<0.001RabeprazoleRabeprazole 20 mg vs. 10 mg: p=0.00520 mg vs. 10 mg: p=0.005

Long-term omeprazole treatment in resistant GERD

LongLong--termterm omeprazoleomeprazole treatmenttreatment in in resistantresistant GERDGERD

•• n=230 n=230 withwith resistanceresistance to Hto H22--blockersblockers•• OmeprazoleOmeprazole ≥≥ 20 mg 20 mg dailydaily•• FollowFollow--upup: 6.5 : 6.5 yearsyears ((rangerange 1.4 1.4 –– 11.2 y)11.2 y)•• At least At least annualannual endoscopyendoscopy

•• 158 158 relapsesrelapses in 1490 in 1490 treatmenttreatment yearsyears (1 per 9.4 (1 per 9.4 yearsyears))•• All All patientspatients rehealedrehealed at at thethe samesame oror higherhigher dosedose•• TheThe treatmenttreatment seemsseems to to bebe safesafe

KlinkenbergKlinkenberg--KnolKnol et al 2000et al 2000

Progression of erosive esophagitisduring long-term PPI treatment

Progression of erosive Progression of erosive esophagitisesophagitisduringduring longlong--termterm PPI PPI treatmenttreatment

•• No No clearclear indicationindication of of progressionprogression to to moremore severesevere esophagitisesophagitis oror stricturestricture

•• DevelopmentDevelopment of Barrettof Barrett´́s has s has beenbeenobservedobserved ((annualannual rate 1.9%), rate 1.9%), butbut thetheauthorsauthors recommendrecommend cautiouscautiousinterpretationinterpretation..

KlinkenbergKlinkenberg--KnolKnol et al 2000et al 2000

ElEl--Serag et al 2004Serag et al 2004

Hazards ratio 0.25 (0.13-0.47, p<0.0001)

N=236Mean age 61.5 y1.170 patient-years of follow-upDysplasia: n=56HGD: n=14

Effect of PPI therapy on theincidence of dysplasia in Barrett´s

EffectEffect of PPI of PPI therapytherapy on on thetheincidenceincidence of of dysplasiadysplasia in Barrettin Barrett´́ss

PPI use may reduce the risk of esophageal cancer

PPI PPI useuse maymay reducereduce thethe riskrisk of of esophagealesophageal cancercancer

•• US VA US VA databasedatabase 1998 1998 –– 20042004–– CancerCancer riskrisk in PPI in PPI consumersconsumers: :

AdjustedAdjusted OR 0.52 [0.40OR 0.52 [0.40--0.70], p<0.00010.70], p<0.0001

•• CaseCase controlcontrol studystudy: 91 : 91 casescases withwith cancercancer ––244 controls 244 controls withwith BarrettBarrett´́s s esophagusesophagus > 2 cm> 2 cm–– CancerCancer riskrisk in PPI in PPI consumersconsumers: OR 0.1 [0.05: OR 0.1 [0.05--0.20]0.20]

KhuranaKhurana et al, Am J Gastroenterol 2005 (A)et al, Am J Gastroenterol 2005 (A)De De JongeJonge et al, Am J Gastroenterol 2006et al, Am J Gastroenterol 2006

AntirefluxAntireflux surgerysurgery

Laparoscopic fundoplication in erosiveand non-erosive reflux disease

LaparoscopicLaparoscopic fundoplicationfundoplication in in erosiveerosiveand and nonnon--erosiveerosive refluxreflux diseasedisease

56564848

8585 **91*91*

00

2020

4040

6060

8080

100100

ResolutionResolutionof of heartburnheartburn

ResolutionResolutionof of mostmost

bothersomebothersomesymptomsymptom

9494++

7979

OverallOverallsatisfiedsatisfied

ErosiveErosive diseasedisease(n=33)(n=33)NonNon--erosiveerosive diseasedisease(n=34)(n=34)

% % successsuccess afterafter 11--3 3 yearsyears

CaseCase controlcontrol studystudyFentonFenton et al 2000 (A)et al 2000 (A)

*p<0.01*p<0.01++p<0.05p<0.05

Drug consumption after antirefluxsurgery in NERD and ERD

Drug Drug consumptionconsumption afterafter antirefluxantirefluxsurgerysurgery in NERD and ERDin NERD and ERD

22

1010

33 3322 22

1010

32*32*

00

1010

2020

3030

4040

5050

NERD (n=60)NERD (n=60) ERD (n=61)ERD (n=61)

AntacidsAntacidsProkineticsProkineticsHH22--blockersblockersPPIsPPIs

% % withwith drugdrug therapytherapy afterafter ARSARS

CaseCase controlcontrol studystudy; median FU 43 ; median FU 43 monthsmonthsThibaultThibault et al 2006et al 2006

*p<0.005*p<0.005

VakilVakil et al 2003et al 2003

Outcome of laparoscopic fundoplication in community hospitals

Outcome of laparoscopic Outcome of laparoscopic fundoplicationfundoplication in community hospitalsin community hospitals

PPIPPI20%20%

NoneNone40%40%

AntacidsAntacids30%30%

Prescription HPrescription H22RARA4%4%

OTC HOTC H22RARA6%6%

Antireflux surgery vs. PPI treatmentLong-term results of a RCT

AntirefluxAntireflux surgerysurgery vs. PPI vs. PPI treatmenttreatmentLongLong--termterm resultsresults of a RCTof a RCT

•• n=298 n=298 randomizedrandomized to to antirefluxantireflux surgerysurgery ororomeprazoleomeprazole 20 mg20 mg

•• FollowFollow--upup 7 7 yearsyears (n=218)(n=218)

LundellLundell et al 2007et al 2007




SurgerySurgery vs.vs. 20 mg 20 mg omeprazoleomeprazole

Log rank p=0.002

66.7%

46.7%




SurgerySurgery vs.vs. 20 20 –– 60 mg mg 60 mg mg omeprazoleomeprazole

Log rank p=0.045




p=0.006 p=0.001

p=0.001




~30% ~30% necessitynecessity of PPI of PPI therapytherapy

LundellLundell et al 2007 (A)et al 2007 (A)

Anti-reflux Surgery Compared withMaintenance Omeprazole for RefluxEsophagitis. Results after 12 Years

AntiAnti--refluxreflux SurgerySurgery ComparedCompared withwithMaintenanceMaintenance OmeprazoleOmeprazole forfor RefluxRefluxEsophagitisEsophagitis. . ResultsResults afterafter 12 12 YearsYears

SurgicalSurgical groupgroup::MaintenanceMaintenance PPI:PPI: 38%38%ReRe--operationoperation: : 5%5%

Esomeprazole vs. Laparoscopic Anti-reflux Surgery for GERD: a 3-year

Interim Analysis of the LOTUS Trial

EsomeprazoleEsomeprazole vs. vs. LaparoscopicLaparoscopic AntiAnti--refluxreflux SurgerySurgery forfor GERD: a 3GERD: a 3--year year

Interim Analysis of Interim Analysis of thethe LOTUS TrialLOTUS Trial

•• Multicenter RCT (11 European Multicenter RCT (11 European countriescountries); n=554); n=554•• StandardizedStandardized ARS ARS vs.vs. esomeprazoleesomeprazole 20 mg (dose 20 mg (dose

adjustmentadjustment to 20 mg to 20 mg b.i.db.i.d. . allowedallowed))•• Definition of Definition of relapserelapse::

–– NecessityNecessity of of antirefluxantireflux medicationmedication ((exceptexcept antacidsantacids) ) ororreoperationreoperation afterafter ARSARS

–– NecessityNecessity of of esomeprazoleesomeprazole > 40 mg per > 40 mg per dayday•• ResultsResults::

LundellLundell et al 2007 (A)et al 2007 (A)

EstimatedEstimated proportionproportion in in remissionremission3 y 3 y afterafter randomizationrandomization::AntirefluxAntireflux surgerysurgery 90%90%EsomeprazoleEsomeprazole 93%93%

€€ x 1,000 per x 1,000 per patientpatient(total (total costscosts in 5 in 5 yearsyears))

MyrvoldMyrvold et al 2001 et al 2001

00

55

1010

1515

2020

DenmarkDenmark FinlandFinland NorwayNorway SwedenSweden

PPI PPI maintenancemaintenanceAntirefluxAntireflux surgerysurgery

Antireflux surgery vs. PPI maintenanceTotal costs after 5 years (RCT)

AntirefluxAntireflux surgerysurgery vs. PPI vs. PPI maintenancemaintenanceTotal Total costscosts afterafter 5 5 yearsyears (RCT)(RCT)

Does antireflux surgery preventcancer development?

DoesDoes antirefluxantireflux surgerysurgery preventpreventcancercancer developmentdevelopment??

0059.43959.439No GERD No GERD n=5,671n=5,671

0.04%0.04%20,11520,115Drug Drug treatmenttreatmentn=1,892n=1,892

0.072%0.072%11,15611,156AntirefluxAntireflux surgerysurgeryn=946n=946

CancerCancer incidenceincidenceFU (FU (patientpatient--yearsyears))

Tran et al 2005Tran et al 2005

Predictors of the response to laparoscopic antireflux surgeryPredictorsPredictors of of thethe responseresponse to to

laparoscopiclaparoscopic antirefluxantireflux surgerysurgery

•• TypicalTypical primaryprimary symptomsymptom•• Abnormal 24Abnormal 24--h pH h pH scorescore•• Response to PPIResponse to PPI

CamposCampos et al, J Gastrointest Surg 1999et al, J Gastrointest Surg 1999

199 199 consecutiveconsecutive patientspatientsExcellentExcellent / good / good outcomeoutcome: 87%: 87%Multiple Multiple logisticlogistic regressionregression analysisanalysis

•• esophagitis documented by endoscopy,esophagitis documented by endoscopy,•• need for continuous PPI therapy,need for continuous PPI therapy,•• abnormal pH monitoring studies,abnormal pH monitoring studies,•• normal esophageal motility studies,normal esophageal motility studies,•• responders to PPI therapy withresponders to PPI therapy with•• persistent volume regurgitation.persistent volume regurgitation.

TheThe best best candidatescandidates forforfundoplicationfundoplication areare thosethose withwith ......

FrestonFreston & & TriadafilopoulosTriadafilopoulos 20042004

EndoscopicEndoscopic therapytherapy

RRadiofreqadiofrequencyuency aapplippliccationation((StrettaStretta))

InjeInjecctiontion / Implantation/ Implantation((EnteryxEnteryx, , GGatekeeperatekeeper))

SSewewinging techniquestechniques((EndoCinchEndoCinch, ESD,, ESD, PLICATOR)PLICATOR)

EndoscopicEndoscopic therapytherapy forfor GERDGERDDevicesDevices

EndoscopicEndoscopic therapytherapy forfor GERDGERDShamSham--controlledcontrolled studystudy of of StrettaStretta

Corley et al 2003

9,5%9,5%9,9%9,9%% of time % of time withwith pHpH < 4 < 4

61%61%55%55%Daily Daily drugdrug intakeintake

30%30%61%61%QoLQoL improvementimprovement > 50%> 50%

33%33%61%61%Relief of Relief of heartburnheartburn

ShamShamStrettaStretta

US US multicentermulticenter studystudy withwith 64 64 patientspatients

ConclusionConclusion::ImprovementImprovement of of symptomssymptoms withoutwithout affectingaffecting

acidacid refluxreflux

Devière et al 2005

n=20n=20n=6*n=6*EnteryxEnteryx afterafter 3 3 monthsmonths

25%25%63%*63%*ImprovementImprovement of of QoLQoL afterafter 3 3 momo..

53%53%78%*78%*ReductionReduction of PPI of PPI ≥≥ 50% 50% afterafter 3 3 momo..

ShamShamn=32n=32

EnteryxEnteryxn=32n=32

US US multicentermulticenter studystudy withwith 64 64 patientspatients

*p<0.05*p<0.05

14,0% 12,7%14,0% 12,7%n=16n=16

13,3% 11,2%13,3% 11,2%n=23n=23

pH < 4 (pH < 4 (BaselineBaseline –– final) final)

EndoscopicEndoscopic therapytherapy forfor GERDGERDShamSham--controlledcontrolled studystudy of of EnteryxEnteryx

ConclusionConclusion::ImprovementImprovement of of symptomssymptoms withoutwithout affectingaffecting

acidacid refluxreflux

WithdrawnWithdrawn becausebecause of of seriousserious sideside effectseffects!!

n = 70

CacaCaca et al 2005et al 2005

EndoscopicEndoscopic therapytherapy forfor GERDGERDLongLong--termterm effecteffect of of EndochinchEndochinch

PLICATOR (NDO Surgical)PLICATOR PLICATOR (NDO Surgical)(NDO Surgical)

Rothstein et al 2006Rothstein et al 2006

EndoscopicEndoscopic therapytherapy forfor GERDGERDShamSham--controlledcontrolled studystudy of PLICATORof PLICATOR

Multicenter RCT: 159 Multicenter RCT: 159 patientspatients withwith PPI PPI dependentdependent GERD GERD and and acidacid refluxreflux demonstrateddemonstrated byby pHpH metrymetry

pHpH metrymetryPPIPPI

Off PPI: 50% Off PPI: 50% vs.vs. 24%24%

Conclusion & RecommendationConclusion & Conclusion & RecommendationRecommendation4


Comparison of alternative strategies forthe long-term management of GERD

ComparisonComparison of alternative of alternative strategiesstrategies forforthethe longlong--termterm managementmanagement of GERDof GERD

LearningLearning curvecurve

Ability to Ability to adjustadjust

Operator Operator dependentdependent

CostCost--effectivenesseffectiveness

SafetySafety

EfficacyEfficacy

ProbablyProbably YesYes

ProbablyProbably YesYes

YesYes

??

MeasurableMeasurablemorbiditymorbidity and and

mortalitymortality

+ (+ (shortshort--termterm))

EndoscopicEndoscopictherapytherapy

YesYes

NoNo

YesYes

< PPI< PPI

MeasurableMeasurablemorbiditymorbidity and and

mortalitymortality

++++++

SurgerySurgery

NoNo

YesYes

NoNo

ProvenProven

No No issuesissues

++++++

PPIPPI

afterafter FennertyFennerty 20052005

•• Initial Initial treatmenttreatment of GERD of GERD shouldshould alwaysalways bebewithwith a PPI a PPI irrespectiveirrespective of of thethe diseasedisease severityseverity..

•• PPIsPPIs areare thethe treatmenttreatment optionoption of of firstfirst choicechoice in in thethe longlong termterm carecare of of patientspatients withwith GERD as GERD as PPIsPPIs areare ……–– effectiveeffective,,–– costcost--effectiveeffective, and, and–– safesafe..

Summary & Conclusions ISummarySummary & & ConclusionsConclusions II

•• AntirefluxAntireflux surgerysurgery isis an an establishedestablished second second lineline optionoption forfor carefullycarefully selectedselected patientspatientssufferingsuffering fromfrom PPIPPI--dependentdependent GERD.GERD.

•• In In experiencedexperienced handshands, ARS , ARS isis as as effectiveeffective as as PPI PPI therapytherapy withwith dose dose adjustmentadjustment..

•• Side Side effectseffects areare moremore commoncommon thanthan withwith PPI PPI therapytherapy..

•• ItIt isis unprovenunproven whetherwhether ARS ARS isis moremore costcost--effectiveeffective thanthan PPI PPI maintenancemaintenance..

Summary & Conclusions IISummarySummary & & ConclusionsConclusions IIII

•• EndoscopicEndoscopic therapytherapy forfor GERD GERD isis still still experimental.experimental.

•• OnlyOnly thethe PLICATORPLICATOR provedproved to to bebe effectiveeffective..•• LongLong--termterm resultsresults areare currentlycurrently notnot availableavailable..•• ComparativeComparative trialstrials withwith establishedestablished antirefluxantireflux

therapiestherapies havehave notnot beenbeen donedone ((oror reportedreported).).

Summary & Conclusions IIISummarySummary & & ConclusionsConclusions IIIIII

•• RefinementRefinement of PPI of PPI therapytherapy•• New New principlesprinciples ((acidacid suppressantssuppressants and and drugsdrugs

withwith different different sitessites of of actionaction))•• CombinationCombination of different of different principlesprinciples ((e.ge.g., ., refluxreflux

blockerblocker and optimal and optimal acidacid suppressantsuppressant in in oneonepillpill))

•• EndoscopicEndoscopic therapytherapy as a test as a test forfor ARSARS•• MultimodalityMultimodality approachapproach, , e.ge.g. PLICATOR plus . PLICATOR plus

PPI, PPI, FundoplicationFundoplication plus PPIplus PPI

Summary & Conclusions IVSummarySummary & & ConclusionsConclusions IVIV

Future Future directionsdirections

Thank you foryour attention !Thank you for

your attention !

j. labenz siegen, germany portoróz june 15, 2007€¦ · june 15, 2007 gastroenterology 2007....

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