Tratamiento crohn

Tratamiento de la enfermedad de Crohn

Ylse Gutiérrez Grobe R2GE

Evolución de la enfermedad

• 50% de los pacientes tendrán alguna complicación en 20 años

• 10% remisión clínica• Incidencia anual de readmisión hospitalaria 20%• 50% requerirá cirugía a los 10 años de Dx• 55% recurrencia postoperatoria en 10 años

Objetivos

Inducir remisión

Mantenerla

Objetivos del tx

Aminorar síntomas

Mejorar la calidad de vida del paciente

Otras metas individuales:

Curación de fístulas

Niños crecimiento normal

Recomendaciones terapéuticas:

Localización de la enfermedad

Severidad de la enfermedad

Complicaciones asociadas

Defin

icion

es•CDAI <150, paciente sintomático, sin secuelas sintomáticas de la

inflamación

Remisión sintomática

•Requieren del uso de dosis convencionales de esteroides para mantener la sensación de bienestar

Dependientes de esteroides

•CDAI 150-220, pacientes ambulatorios, sin deshidratación ni datos de toxicidad sistémica, dolor, obstrucción y masas abdominales, pérdida de peso <10%

Enfermedad leve-moderada

•CDAI 220-450, no responden al tratamiento para leve-moderada, síntomas mas prominentes , náusea y vómito (sin obstrucción), anemia y pérdida significativa de peso

Enfermedad moderada a severa

•CDAI >450, síntomas a pesar de esteroides y biológicos, fiebre, vómito con evidencia de obstrucción intestinal, irritación peritoneal, caquexia, presencia de absceso

Enfermedad severa/ fulminante

El abordaje terapéutico es individualizado

Respuesta sintomática

Tolerancia a la intervención médica

Tratar enfermedad aguda

Inducción a la remisión

Mantenimiento de la remisión

Medidas generales

La duración del tratamiento para enfermedad activa se deberá continuar hasta la remisión sintomática o falla

Inicia 2-4 semanas

Mejoría máxima 12-16 semanas

Con remisión clínica considerar Tx mantenimiento

Lichtenstein G, Management of Crohn´s disease In adults. Am J Gastroenterol. 2009; 104:465-483

Síntomas

AlternativoLeve a

moderada

AvanzadoModerado a

severo

Terapia secuencial

La terapia se progresa de acuerdo a la severidad al inicio o falla al paso previo

Aminosalicilatos

Corticosteroides

Anti-TNFCiclosporina

Severidad al momento del diagnóstico

Severa

Moderada

Leve

AminosalicilatosTiopurinas

Aminosalicilatos

Anti-TNFTiopurinas

Inducción

Mantenimiento

Colectomía

Generalidades

Inducción

Sulfasalazina

Mesalazina

Esteroides

Azatioprina/6-MP

Metotrexato

Biológicos

Mantenimiento

Sulfasalazina

Mesalazina

Azatioprina/6-MP

Metotrexato

Biológicos

Tx farmacológico

5-ASA

La evidencia no es suficiente

Mesalazina 4g/d efectivo en leve a moderada

Sulfasalazina 4-6 g/día mejor para actividad colónica

Mesalazina no es superior que placebo para mantener la remisión

Mowat C, Cole A. Guidelines for the management of inflammatory bowel disease in adults. Gut 2011;60:571-607

5-ASA

Sulfasalazina 3-6 g/día

Mejor que placebo~43% tasa de remisión vs placebo 30%

No efectivo en enfermedad de ID

Mesalazina ECA 40-55% remisión

Meta-analisisMesalamine 4g/day

Estadísticamente significativo pero no clínicamente

Akobeng et al Cochrane Database of Systematic Reviews 2009

Aminosalicylates for induction of remission or response in

Crohn’sdisease (Review)

Lim WC, Hanauer S

Thisisareprint of aCochranereview, prepared and maintained byTheCochraneCollaboration and published in TheCochraneLibrary

2010, Issue12

http://www.thecochranelibrary.com

Aminosalicylatesfor induction of remission or response in Crohn’s disease (Review)

Copyright © 2010 The Cochrane Collaboration. Published by John W iley & Sons, Ltd.

Aminosalicylates for induction of remission or response in

Crohn’s disease (Review)

Lim WC, Hanauer S


2010, Issue12


Aminosalicylatesfor induction of remission or response in Crohn’s disease (Review)


Cochrane Database of Systematic Reviews 2010, Issue 12

D I S C U S S I O N

Thefocusof thisreviewwasbroad, and all information pertaining

to the efficacy of sulfasalazine or 5-ASA alone for the treatment

of mildly to moderately activeCrohn’sdiseasewhen compared to

placebo, corticosteroids, and other aminosalicylates (alone or in

combination with corticosteroids) wassought. To ensure that ef-

fect estimateswereinterpretableand clinically meaningful in this

review where trials were anticipated to be diverse with different

aminosalicylateformulations, dosages, comparatorsand outcome,

each combination wasconsidered separatelyand only resultsfrom

similar trialsweresynthesized. A random effectsmodel wasused

for pooling data as it allowed between-trial variability to be ac-

counted for in theoverall estimate, producing moreconservative

resultswith wider 95% confidenceintervals. Resultsbased on the

fixed effectsmodel and duration of therapy werealso presented in

sensitivity analysesplanned apriori and thesedid not significantly

alter theresultsobtained with therandom effectsmodel or when

trialswith different duration of treatment wereincluded.

The results showed that sulfasalazine at 3 to 6 g/day had only

modest efficacy over placebo. A pooled RR of 1.38 wasobtained,

that is, patientstreated with sulfasalazinehada38%higher chance

of achieving remission than placebo-treated patients. Thisbenefit

was limited to patients with Crohn’s colitis. Patients with small

bowel diseaseor thosewhocontinued tohaveactivediseasedespite

previouscorticosteroid and sulfasalazinetreatment werenot likely

tobenefit. Sulfasalazinewaslesseffectivethan corticosteroidswith

pooled RR of 0.66, that is, sulfasalazine-treated patientshad 34%

lesschanceof achieving remission than corticosteroid-treated pa-

tients. In addition, sulfasalazine monotherapy was less effective

than combination therapy with corticosteroids. The question of

whether sulfasalazineisauseful adjunct to corticosteroid therapy,

while not the primary focus of this review, was addressed in the

TAS (Trial of adjunctive sulfasalazine in Crohn’s disease) study

(Singleton 1979) and ECCDS: 74% (34/56) and 83% (39/47)

in thecorticosteroid group versus58% (25/43) and 79% (44/56)

in the combination group achieved remission (CDAI < 150) at

theend of 8 weeksand 18 weeksrespectively (P = 0.12 and 0.57

respectively) with a pooled RR of 1.12 (95% CI 0.94 to 1.33)

(See Figure 2), demonstrating that sulfasalazine was not a use-

ful adjunct to corticosteroid therapy. Thesedatasuggest that sul-

fasalazinemay beused asfirst linetherapy for patientswith mildly

to moderately active Crohn’s colitis, reserving the more potent

corticosteroids for patients failing sulfasalazine therapy. This is

consistent with thepharmacology of sulfasalazine, an azo-bonded

prodrug that requires colonic bacteria azo-reductases for the re-

leaseand targeted deliveryof active5-ASA moiety to thecolon. In

contrast, olsalazine, anew azo-bonded 5-ASA dimer, wasshown

to lack therapeuticeffect, with asignificant proportion developing

worseningdiarrhea(Wright 1995). Thisisacommon and unique

dose-related complication of olsalazinetherapy, aconsequenceof

increased ileal secretion and gastrointestinal transit (Rao 1987;

Wadworth 1991; Sandborn 2002a).

Figure 2.

While mesalamine has similar efficacy to sulfasalazine when

equimolar doses are used in ulcerative colitis (3 to 6 g of sul-

fasalazine isequivalent to 1.2 to 2.4 g of mesalamine), low dose

controlled-release mesalamine (Pentasa at 1 to 2 g/day) was not

moreeffectivethanplaceboat inducingremission inactiveCrohn’s

disease (Comparison 04, Outcome 02). Predictably, delayed-re-

lease mesalamine (Salofalk at 2 g/day) was less efficacious than

corticosteroids(Scholmerich 1990).

On the other hand, trials assessing higher doses of mesalamine

produced conflicting results. Thepositiveeffect of controlled-re-

lease mesalamine (Pentasa) at 4 g/day in one study (Singleton

1993) was in contrast to the lack of effect in similarly designed

trials (Singleton 1994; Crohn III 1997). Moderate heterogene-

ity and rather largeplacebo effectscould havereduced thepower

to detect astatistically significant differencebetween placebo and

18Aminosalicylatesfor induction of remission or response in Crohn’s disease (Review)


D A T A A N D A N A L Y S E S

Comparison 1. Sulfasalazineversusplacebo

Outcomeor subgroup titleNo. of

studies

No. of

participants Statistical method Effect size

1 Induction of remission (CDAI

<150), therapeutic response

(VHI decrease>=25%) or

clinical improvement

3 289 Risk Ratio (M-H, Random, 95% CI) 1.51 [0.97, 2.35]


<150)


Comparison 2. Sulfasalazineversuscorticosteroids


studies

No. of



<150)


Comparison 3. Sulfasalazineversussulfasalazineand corticosteroids


studies

No. of


1 Induction of remission 1 110 Risk Ratio (M-H, Random, 95% CI) 0.64 [0.47, 0.86]

Comparison 4. Controlled-releasemesalamine(1-2 g/day) versusplacebo


studies

No. of


1 Decrease in CDAI >=50, HBI

>=2 or improvement/remission

(asdefined by Tvedeet al)


1.1 1 g/day 1 120 Risk Ratio (M-H, Random, 95% CI) 0.91 [0.56, 1.46]

1.2 1.5 g/day 2 107 Risk Ratio (M-H, Random, 95% CI) 1.47 [0.87, 2.49]





Comparison 1. Sulfasalazineversusplacebo


studies

No. of



<150), therapeutic response

(VHI decrease >=25%) or

clinical improvement



<150)


Comparison 2. Sulfasalazineversuscorticosteroids


studies

No. of



<150)


Comparison 3. Sulfasalazineversussulfasalazineand corticosteroids


studies

No. of


1 Induction of remission 1 110 Risk Ratio (M-H, Random, 95% CI) 0.64 [0.47, 0.86]

Comparison 4. Controlled-release mesalamine(1-2 g/day) versusplacebo


studies

No. of


1 Decrease in CDAI >=50, HBI

>=2 or improvement/remission

(asdefined by Tvedeet al)



1.2 1.5 g/day 2 107 Risk Ratio (M-H, Random, 95% CI) 1.47 [0.87, 2.49]




5-ASA efectos adversos

Sulfasalazina Cefalea

Náusea/vómito

Rash

Malabsorción de folatos

Oligospermia reversible

Pancreatitis

Supresión de la médulaósea

Exacerbación paradójica

Nefritis intersticial

Mesalazina

Cefalea

Náusea

Rash

Pancreatitis

Exacerbación paradójica

Nefritis intersticial

Esteroides

Eficacia superior a placebo, antibióticos y mesalazina

Inhiben la activación de Linf T y la producción de citocinas proinflamatorias

Munkholm et al 36% dependientes; 20% resistentes a 1 años


Esteroides

Remisión sintomática pero no curación de la mucosa

La mayoría no mantienen remisión a un año después del primer ciclo de esteroide

36% dependientes, 20% resistentes

Prednisona 40 mg a dosis de reducción a 8 semanas

Budesonida9mg/día


No mantenimiento de la remisión

Traditional corticosteroids for induction of remission in

Crohn’sdisease (Review)

Benchimol EI, Seow CH, Steinhart AH, GriffithsAM


2010, Issue4


Traditional corticosteroidsfor induction of remission in Crohn’sdisease (Review)





Thisisareprint of aCochranereview, prepared and maintained by TheCochraneCollaboration and published in TheCochraneLibrary

2010, Issue4


Traditional corticosteroidsfor induction of remission in Crohn’s disease (Review)



Comparison 1. Corticosteroidsvs. placebo


studies

No. of


1 Remission rate(Late, 15+ weeks) 2 267 Risk Ratio (M-H, Fixed, 95% CI) 1.99 [1.51, 2.64]

2 Development of Any Adverse

Event

1 Risk Ratio (M-H, Fixed, 95% CI) Totalsnot selected

3 Withdrawal From Study DueTo

AdverseEvent

2 267 Risk Ratio (M-H, Fixed, 95% CI) 4.57 [0.75, 27.83]

4 Responseto Treatment 1 Risk Ratio (M-H, Fixed, 95% CI) Totalsnot selected

Comparison 2. Corticosteroidsvs. 5-ASA


studies

No. of


1 Remission Rate (Late, 15+

weeks) (Max Pred 60 mg/day +

5-ASA 1.2-2 g/day)


2 Remission Rate (Late, 15+

weeks) (Sensitivity Analysis-

Sulfasalazinestudiesonly)



Event



Event (Sensitivity Analysis-

Removed high-dose 5-ASA

studies)


5 Withdrawal from Study Dueto

AdverseEvent


6 Responseto Treatment 2 Risk Ratio (M-H, Fixed, 95% CI) Totalsnot selected

22Traditional corticosteroidsfor induction of remission in Crohn’s disease (Review)


Analysis 1.1. Comparison 1 Corticosteroids vs. placebo, Outcome 1 Remission rate (Late, 15+ weeks).

Review: Traditional corticosteroids for induction of remission in Crohn’sdisease

Comparison: 1 Corticosteroidsvs. placebo

Outcome: 1 Remission rate (Late, 15+ weeks)

Study or subgroup Corticosteroids Placebo Risk Ratio Weight Risk Ratio

n/N n/N M-H,Fixed,95%CI M-H,Fixed,95%CI

Malchow 1984 39/47 22/58 48.4 % 2.19 [ 1.54, 3.12 ]

Summers 1979 40/85 20/77 51.6 % 1.81 [ 1.17, 2.81 ]

Total (95% CI) 132 135 100.0 % 1.99 [ 1.51, 2.64 ]

Total events: 79 (Corticosteroids), 42 (Placebo)

Heterogeneity: Chi2 = 0.45, df = 1 (P= 0.50); I2 =0.0%

Test for overall effect: Z = 4.82 (P < 0.00001)

0.1 0.2 0.5 1 2 5 10

Favours placebo Favours steroids

Analysis 1.2. Comparison 1 Corticosteroids vs. placebo, Outcome 2 Development of Any Adverse Event.


Comparison: 1 Corticosteroidsvs. placebo

Outcome: 2 Development of Any Adverse Event

Study or subgroup Corticosteroids Placebo Risk Ratio Risk Ratio


Summers 1979 27/85 5/77 4.89 [ 1.98, 12.07 ]

0.01 0.1 1 10 100

Placebo Events Steroid Events



Analysis 2.1. Comparison 2 Corticosteroids vs. 5-ASA, Outcome 1 Remission Rate (Late, 15+ weeks) (Max

Pred 60 mg/day + 5-ASA 1.2-2 g/day).


Comparison: 2 Corticosteroidsvs. 5-ASA

Outcome: 1 Remission Rate (Late, 15+ weeks) (Max Pred 60 mg/day + 5-ASA 1.2-2 g/day)

Study or subgroup Corticosteroids 5-ASA Risk Ratio Weight Risk Ratio


Malchow 1984 39/47 27/54 37.8 % 1.66 [ 1.23, 2.23 ]

Scholmerich 1990 21/32 8/30 12.4 % 2.46 [ 1.29, 4.69 ]

Summers 1979 51/85 31/74 49.8 % 1.43 [ 1.04, 1.97 ]

Total (95% CI) 164 158 100.0 % 1.65 [ 1.33, 2.03 ]

Total events: 111 (Corticosteroids), 66 (5-ASA)

Heterogeneity: Chi2 = 2.23, df = 2 (P= 0.33); I2 =10%

Test for overall effect: Z = 4.64 (P < 0.00001)

0.1 0.2 0.5 1 2 5 10

Favours 5-ASA Favours steroids

Analysis 2.2. Comparison 2 Corticosteroids vs. 5-ASA, Outcome 2 Remission Rate (Late, 15+ weeks)

(Sensitivity Analysis - Sulfasalazine studies only).


Comparison: 2 Corticosteroidsvs. 5-ASA

Outcome: 2 Remission Rate (Late, 15+ weeks) (Sensitivity Analysis - Sulfasalazine studiesonly)

Study or subgroup Corticosteroids Sulfasalazine Risk Ratio Weight Risk Ratio


Malchow 1984 39/47 27/54 43.1 % 1.66 [ 1.23, 2.23 ]

Summers 1979 51/85 31/74 56.9 % 1.43 [ 1.04, 1.97 ]

Total (95% CI) 132 128 100.0 % 1.53 [ 1.23, 1.91 ]

Total events: 90 (Corticosteroids), 58 (Sulfasalazine)

Heterogeneity: Chi2 = 0.45, df = 1 (P= 0.50); I2 =0.0%

Test for overall effect: Z = 3.78 (P = 0.00016)

0.1 0.2 0.5 1 2 5 10

Favours sulfasalazin Favours steroids



Budesonide for maintenance of remission in Crohn’sdisease

(Review)

Benchimol EI, Seow CH, Otley AR, Steinhart AH

Thisisareprint of aCochranereview, preparedand maintained byTheCochraneCollaboration and published in TheCochraneLibrary

2009, Issue1


Budesonide for maintenance of remission in Crohn’sdisease (Review)





Thisisareprint of aCochranereview, prepared and maintained by TheCochraneCollaboration and published in TheCochraneLibrary

2010, Issue4


Traditional corticosteroidsfor induction of remission in Crohn’s disease (Review)


Analysis 4.1. Comparison 4 Budesonide 9 mg vs 6 mg, Outcome 1 Maintenance of Clinical Remission.

Review: Budesonide for maintenance of remission in Crohn’s disease

Comparison: 4 Budesonide 9 mg vs6 mg

Outcome: 1 Maintenance of Clinical Remission

Study or subgroup 9 mg 6 mg Risk Ratio Risk Ratio


de Jong 2007 66/81 58/76 1.07 [ 0.91, 1.26 ]

0.1 0.2 0.5 1 2 5 10

Favours 6 mg Favours 9 mg

Analysis 4.2. Comparison 4 Budesonide 9 mg vs 6 mg, Outcome 2 Change in CDAI from baseline.



Outcome: 2 Change in CDAI from baseline

Study or subgroup Budesonide 9 mg Budesonide 6 mgMean

DifferenceMean

Difference

N Mean(SD) N Mean(SD) IV,Fixed,95%CI IV,Fixed,95%CI

1 12 months

de Jong 2007 81 15 (72.81) 76 33 (74.5) -18.00 [ -41.06, 5.06 ]

-100 -50 0 50 100


48Budesonide for maintenance of remission in Crohn’sdisease (Review)


Analysis 4.1. Comparison 4 Budesonide 9 mg vs 6 mg, Outcome 1 Maintenance of Clinical Remission.




Study or subgroup 9 mg 6 mg Risk Ratio Risk Ratio


de Jong 2007 66/81 58/76 1.07 [ 0.91, 1.26 ]

0.1 0.2 0.5 1 2 5 10


Analysis 4.2. Comparison 4 Budesonide 9 mg vs 6 mg, Outcome 2 Change in CDAI from baseline.



Outcome: 2 Change in CDAI from baseline

Study or subgroup Budesonide 9 mg Budesonide 6 mgMean

DifferenceMean

Difference

N Mean(SD) N Mean(SD) IV,Fixed,95%CI IV,Fixed,95%CI

1 12 months

de Jong 2007 81 15 (72.81) 76 33 (74.5) -18.00 [ -41.06, 5.06 ]

-100 -50 0 50 100




Analysis 4.5. Comparison 4 Budesonide 9 mg vs 6 mg, Outcome 5 W ithdrawals Due to Adverse Events.



Outcome: 5 WithdrawalsDue to Adverse Events

Study or subgroup Budesonide 9 mg Budesonide 6 mg Risk Ratio Risk Ratio


de Jong 2007 1/81 3/76 0.31 [ 0.03, 2.94 ]

0.01 0.1 1 10 100

6 mg withdrawals 9 mg withdrawals

Analysis 5.1. Comparison 5 Budesonide 9 mg/day vs prednisolone 40 mg/day (weaning), Outcome 1

Maintenance of Clinical Remission.


Comparison: 5 Budesonide 9 mg/day vsprednisolone 40 mg/day (weaning)


Study or subgroup Budesonide Prednisolone Risk Ratio Risk Ratio


1 3 months

Schoon 2005 27/46 32/44 0.81 [ 0.60, 1.09 ]

2 6 months

Schoon 2005 24/46 29/44 0.79 [ 0.56, 1.12 ]

3 12 months

Schoon 2005 23/46 28/44 0.79 [ 0.55, 1.13 ]

0.1 0.2 0.5 1 2 5 10

Favours prednisolone Favours budesonide



Analysis 5.4. Comparison 5 Budesonide 9 mg/day vs prednisolone 40 mg/day (weaning), Outcome 4

Abnormal ACTH Stimulation Test.


Comparison: 5 Budesonide 9 mg/day vsprednisolone 40 mg/day (weaning)

Outcome: 4 Abnormal ACTH Stimulation Test

Study or subgroup Budesonide Prednisolone Risk Ratio Weight Risk Ratio


Schoon 2005 13/36 20/33 100.0 % 0.60 [ 0.36, 1.00 ]

Total (95% CI) 36 33 100.0 % 0.60 [ 0.36, 1.00 ]

Total events: 13 (Budesonide), 20 (Prednisolone)

Heterogeneity: not applicable

Test for overall effect: Z = 1.97 (P= 0.048)

0.1 0.2 0.5 1 2 5 10

Pred Group Abnorm Bud Group Abnorm

Analysis 6.1. Comparison 6 Budesonide 6 mg vs mesalamine 3 g/day, Outcome 1 Maintenance of clinical

remission.


Comparison: 6 Budesonide 6 mg vsmesalamine 3 g/day

Outcome: 1 Maintenance of clinical remission

Study or subgroup Budesonide Mesalamine Risk Ratio Risk Ratio


Mantzaris2003 13/29 5/28 2.51 [ 1.03, 6.12 ]

0.1 0.2 0.5 1 2 5 10

Favours 5-ASA Favours budesonide



Antibióticos

Se ha usado de manera empírica, y hacen falta estudios para demostrar su eficacia

Las bacterias entéricas juegan un papel en algunas complicaciones de la EC

Los más comunes son metronidazol y ciprofloxacino

Antibióticos

Metronidazol

Tratamiento para enfermedad perianal

20 mg/kg/día x 3 meses reduce el riesgo de recurrencia post a la resección ileocecal

Ciprofloxacino

Eficacia similar que el metronidazol para enfermedad perianal


Antibiotics and Inflammatory Bowel Diseases

Dig Dis 2013;31:379–384DOI: 10.1159/000354704

381

Gut mucosa is separated from the intestinal lumen by a mucous layer. After mucous layer removal, aerobic cul-ture of colonic biopsies in CD patients shows a high con-centration of bacteria, primarily Escherichia coli , while in healthy individuals it is sterile [25] . An increased pres-ence of E. coli , particularly the adherent-invasive E. coli (AIEC) pathovar, has been reported by several studies in CD tissue [3, 26, 27] . Pathogenic AIEC are able to colo-nize the intestinal mucosa by adhering to epithelial cells, to invade these cells, and to survive and replicate within macrophages, inducing the secretion of large amounts of tumor necrosis factor-α [28] . Nowadays, AIEC are per-haps the most likely candidate organisms in promoting the CD inflammatory process. In addition, a decreased number of protective bifidobacteria, lactobacilli and the more recently studied Faecalibacterium prausnitzii, Bac-teroide fragilis and Firmicutes , has been reported in CD patients [25, 29] .

Genetic susceptibly in some subjects with CD is related to polymorphisms in the NOD2/CARD15 gene, suggest-ing that individuals with mutations in NOD2 present de-fective intestinal immune responses to gut microbiota. About 20% of CD patients are homozygous for NOD2 variants and they may have an increased susceptibility to CD localized at the ileum [30] . Moreover, a loss of immu-nologic tolerance to the commensal flora has been ob-served in patients with active IBD [31] . On the assump-tion of these and other data, antibiotics are employed as primary therapy for treatment of acute flares, and for postoperative recurrence prevention [32–34] .

Antibiotics as Primary Therapy in Active Crohn’s Disease The data supporting the role of AIEC in the pathogen-

esis of CD provide the rationale for a therapeutic manipu-lation of the intestinal flora through the use of antibiotics active against these bacteria. Some antibiotics, such as clarithromycin and ciprofloxacin, are able to penetrate macrophages and may therefore be effective in eradicating the bacteria. However, a randomized, placebo-controlled trial performed with clarithromycin, at a dose of 1 g for 3 months, in 41 patients with active CD, was stopped because no difference in the remission or response rate between the antibiotic and placebo was observed [35] .

Metronidazole and ciprofloxacin are the most fre-quent studied and employed antibiotics, even though their role as primary therapy in active CD remains con-troversial. Metronidazole, active against some parasites and most anaerobic bacteria, including Bacteroides and Clostridium species, was first reported to be effective in CD in an open study in 1975 [36] . Ciprofloxacin is a qui-nolone derivative with a selective suppressive effect on the intestinal microflora. Not only E. coli , but also other Enterobacteriaceae are especially sensitive to this antibi-otic, which, on the contrary, does not particularly affect anaerobic bacteria.

Several randomized clinical trials have evaluated the efficacy of these antibiotics, used alone or in combina-tion, at inducing remission in CD ( table 2 ) [35, 37–42] . The results of these studies have shown that patients with colonic localization get more benefit from antibiotics, probably because of the higher bacterial concentration in the colon than in the small bowel. In addition, the asso-

Table 2. Antibiotic trials as primary therapy in acute flares

Reference (first author) Antibiotic (dose) Patients, n Time, weeks

Control Remission, %

act ive control

Ursing, 1982 [37] metronidazole (800 mg/day) 78 16 sulfasalazine NSSutherland, 1991 [38] metronidazole (10 or 20 mg/kg) 99 16 placebo 27 25

36Colombel, 1999 [39] ciprofloxacin (500 mg bid) 40 6 mesalamine 56 55Arnold, 2002 [40] ciprofloxacin (500 mg bid) 47 26 placebo p < 0.001Prantera, 1996 [41] ciprofloxacin (500 mg bid) +

metronidazole (500 mg bid)41 12 methylprednisolone

0.7–1 mg/kg45.5 63

Greenbloom, 1998 [42] ciprofloxacin (500 mg bid) +metronidazole (250 mg tid)

72 10 – 68 –

Leiper, 2008 [35] clarithromycin (1,000 mg/day) 41 12 placebo 26 27

NS = Not significant.

Do

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Dig Dis 2013;31:379–384

Probiotics for induction of remission in Crohn’sdisease

(Review)

Butterworth AD, ThomasAG, AkobengAK


2009, Issue1


Probioticsfor induction of remission in Crohn’sdisease (Review)


Probiotics for induction of remission in Crohn’s disease

(Review)

Butterworth AD, ThomasAG, Akobeng AK


2009, Issue1


Probiotics for induction of remission in Crohn’s disease (Review)



Comparison 1. Probioticsversusplacebo


studies

No. of


1 Induction of remission 1 11 OddsRatio (M-H, Fixed, 95% CI) 0.09 [0.04, 17.20]

Analysis 1.1. Comparison 1 Probiotics versus placebo, Outcome 1 Induction of remission.

Review: Probiotics for induction of remission in Crohn’sdisease

Comparison: 1 Probioticsversusplacebo

Outcome: 1 Induction of remission

Study or subgroup Treatment Control OddsRatio Weight OddsRatio


Schultz 2004 4/5 5/6 100.0 % 0.80 [ 0.04, 17.20 ]

Total (95% CI) 5 6 100.0 % 0.80 [ 0.04, 17.20 ]

Total events: 4 (Treatment), 5 (Control)



0.1 0.2 0.5 1.0 2.0 5.0 10.0

Favours L. GG Favours placebo

W H A T ’ S N E W

Last assessed asup-to-date: 20 April 2008.

12 May 2008 Amended Converted to new review format.

10Probiotics for induction of remission in Crohn’s disease (Review)


.

Cochrane Database of Systematic Reviews 2008, Issue 3.

Tiopurinas

Efectivas para inducir remisión y mantenimiento

AZA/MP

AZA 2-2.5 mg/kg/día y MP 0.75-1.5 mg/kg/día

INICIAR

2 o mas cursos de esteroide en 12 meses

Recaída a dosis menores de 15 mg/día

Recaída 6 semanas después de haber suspendido esteroide


Gut1995;37:674-678

Gastroenterology 2013;145:1464–1478

Azathioprine or 6-mercaptopurine for maintenance of

remission in Crohn’s disease (Review)

PrefontaineE, Sutherland LR, MacDonald JK, Cepoiu M


2009, Issue1


Azathioprine or 6-mercaptopurine for maintenance of remission in Crohn’s disease (Review)






2009, Issue1





Comparison 1. Maintenanceof remission


studies

No. of


1 Maintenance of remission

(Azathioprine)

7 463 Peto OddsRatio (Peto, Fixed, 95% CI) 2.32 [1.55, 3.49]

1.1 Azathioprine dose 2.5

mg/kg/day



mg/kg/day



mg/kg/day


2 Maintenance of remission

(6-MP, 50 mg/day)


Comparison 2. Steroid SparingEffect


studies

No. of


1 Final prednisone dose < 10

mg/day


1.1 Steroid sparing effect 2 30 Peto OddsRatio (Peto, Fixed, 95% CI) 5.22 [1.06, 25.67]

Comparison 3. AdverseEvents(Toxicity)


studies

No. of


1 Withdrawalsdue to adverse

events(Azathioprine)


2 Withdrawalsdue to adverse

events(6-MP)


14Azathioprine or 6-mercaptopurine for maintenance of remission in Crohn’s disease (Review)


Analysis1.1. Comparison 1 Maintenance of remission, Outcome 1 Maintenance of remission (Azathioprine).

Review: Azathioprine or 6-mercaptopurine for maintenance of remission in Crohn’sdisease

Comparison: 1 Maintenance of remission

Outcome: 1 Maintenance of remission (Azathioprine)

Study or subgroup Treatment ControlPeto

OddsRatio WeightPeto

OddsRatio

n/N n/N Peto,Fixed,95%CI Peto,Fixed,95%CI

1 Azathioprine dose 2.5 mg/kg/day

Candy 1995 14/25 2/20 11.3 % 7.12 [ 2.11, 23.99 ]

Summers 1979 16/19 15/20 7.1 % 1.73 [ 0.37, 8.05 ]

Subtotal (95% CI) 44 40 18.3 % 4.13 [ 1.59, 10.71 ]


Heterogeneity: Chi2 = 2.00, df = 1 (P = 0.16); I2 =50%



D’Haens 2007 18/32 9/29 16.5 % 2.73 [ 1.00, 7.45 ]

Lemann 2005 38/40 36/43 8.8 % 3.17 [ 0.80, 12.54 ]

O’Donoghue 1978 13/23 8/27 13.4 % 2.95 [ 0.97, 9.00 ]

Rosenberg 1975 7/10 4/10 5.6 % 3.16 [ 0.57, 17.62 ]

Willoughby 1971 4/5 2/5 2.9 % 4.48 [ 0.41, 49.42 ]

Subtotal (95% CI) 110 114 47.2 % 3.01 [ 1.66, 5.45 ]


Heterogeneity: Chi2 = 0.15, df = 4 (P = 1.00); I2 =0.0%



Summers 1979 37/54 65/101 34.5 % 1.20 [ 0.60, 2.41 ]

Subtotal (95% CI) 54 101 34.5 % 1.20 [ 0.60, 2.41 ]




Total (95% CI) 208 255 100.0 % 2.32 [ 1.55, 3.49 ]


Heterogeneity: Chi2 = 7.75, df = 7 (P = 0.36); I2 =10%


Test for subgroup differences: Chi2 = 5.60, df = 2 (P= 0.06), I2 =64%

0.1 0.2 0.5 1 2 5 10

Favours placebo Favours azathioprine



Analysis 1.2. Comparison 1 Maintenance of remission, Outcome 2 Maintenance of remission (6-MP, 50

mg/day).

Review: Azathioprine or 6-mercaptopurine for maintenance of remission in Crohn’s disease

Comparison: 1 Maintenance of remission

Outcome: 2 Maintenance of remission (6-MP, 50 mg/day)



OddsRatio


Hanauer 2004 24/47 9/40 100.0 % 3.32 [ 1.40, 7.87 ]

Total (95% CI) 47 40 100.0 % 3.32 [ 1.40, 7.87 ]




Test for subgroup differences: Not applicable

0.1 0.2 0.5 1 2 5 10

Favours placebo Favours 6-MP

Analysis 2.1. Comparison 2 Steroid Sparing Effect, Outcome 1 Final prednisone dose < 10 mg/day.

Review: Azathioprine or 6-mercaptopurine for maintenance of remission in Crohn’s disease

Comparison: 2 Steroid Sparing Effect

Outcome: 1 Final prednisone dose < 10 mg/day



OddsRatio


1 Steroid sparing effect

Rosenberg 1975 8/10 4/10 83.5 % 4.87 [ 0.85, 27.86 ]

Willoughby 1971 5/5 4/5 16.5 % 7.39 [ 0.15, 372.38 ]

Total (95% CI) 15 15 100.0 % 5.22 [ 1.06, 25.67 ]


Heterogeneity: Chi2 = 0.04, df = 1 (P = 0.85); I2 =0.0%


Test for subgroup differences: Not applicable

0.02 0.1 1 10 50

Favours placebo Favours azathioprine



Metotrexate

Efectivo para inducir remisión y para el mantenimiento

Puede inducir curación de la mucosa

25 mg/semana IM mejor que

No recomendación firme respecto a la duración

Uso prolongado asocia a mayor remisión

Methotrexate for maintenance of remission in Crohn’sdisease

(Review)

Patel V, MacDonald JK, McDonald JWD, ChandeN


2009, Issue4


Methotrexate for maintenance of remission in Crohn’sdisease (Review)






2009, Issue1




Maté-Jiménez 2000: Jadad score= 2 (A 1, B 0, C 0, D 0, E 1).

Allocation concealment was unclear and blinding was not used.

Thisstudy wasdetermined to haveahigh risk of bias(SeeFigure

1)

Oren 1997: Jadad score= 4 (A 1 , B 0, C 1, D 1, E 1). Alloca-

tion concealment wasunclear. Although themanuscript doesnot

describemethodsused for randomization and allocation conceal-

ment thesemethodswerelikely to beadequatebased on adequate

methods described in other published studies by these authors.

Theoverall risk of biasishigher than that of theFeagan study but

much lower than theMate-Jiminez study (SeeFigure1).

Effects of interventions

Feagan 2000

After 40 weeksof treatment, relapseoccurred in 14 of 40 (35%)

patientsassigned methotrexateand 22 of 36 (61%) patientsgiven

placebo (OR 0.36; 95% CI 0.15 to 0.87; P=0.02). The NNT

(number needed to treat) to prevent onerelapsewas4. Themean

time to relapse with methotrexate was > 40 weeks, and with

placebo it was 22 weeks. Of the 36 patients who relapsed, 22

were subsequently treated with methotrexate 25 mg IM weekly.

Twelve(55%) of thesepatientsagain werein remission at week 40

compared to 2 of 14 patients (14%) who were not treated with

methotrexateafter relapse. Theoverall incidenceof adverseevents

wassimilar inboth groups. Common adverseeventsincludednau-

seaand vomiting, symptomsof acold, abdominal pain, headache,

joint pain or arthralgia, and fatigue. Noneof thepatients in the

methotrexategroup had aseriousadverseevent compared to two

in theplacebo group (cervical dysplasiaand viral respiratory tract

infection. Onemethotrexatepatient withdrew from thestudy be-

causeof nausea.

Oren 1997

Theproportion of patientsentering first remission was10 of 26

(38%) in the MTX group, 13 of 32 (41%) in the 6-MP group,

and 12 of 26 (46%) in theplacebo group. Thesedifferenceswere

not statistically significant. Nine patients receiving MTX (90%;

95% CI 57% to >99.9%) maintained remission after induction

compared to 8 patients receiving 6-MP (62%; 95% CI 35% to

82%) and 8 patients receiving placebo (67%; 95% CI 39% to

86%). Therewereno statistically significant differencesbetween

the threegroups. The time to first remission and to first relapse

data were similar in all groups (data not available). The MTX

group did show agreater mean total time (months) in remission

and proportion of total study time in remission, but the results

werenot statistically significant (datanot available). Onepatient

in theMTX group withdrew dueto an adverseevent (headache)

comparedtoonepatient in the6-MPgroup(leukopeniaandstom-

atitis) and nonein theplacebo group.

Maté-Jiménez2000

After completing 30 weeks of induction treatment, 28 total pa-

tients with CD had achieved remission, including 15 of 16 pa-

tients(94%) in the6-MP group, 12 of 15 patients (80%) in the

MTX group, and 1 of 7 patients(14%) in the5-ASA group. After

76 weeksof treatment 8 of 12 MTX patientsmaintained remis-

sion compared to 8 of 15 6-MPpatientsand zero5-ASA patients.

Thesedifferenceswerenot statistically significant. Maté-Jiménez

2000 did not report adverse events separately for patients with

ulcerativecolitisand Crohn’sdisease. Adverseeventsexperienced

by patients who received MTX included nausea and dyspepsia,

mild alopecia, mild increasein AST levels, peritoneal abscess, hy-

poalbuminemia, severerash and atypical pneumonia. Threeof 26

patientstreated with MTX withdrew dueto adverseeventscom-

pared to 4 of 30 patientstreated with 6-MP.

Pooled analyses

MethotrexateversusplaceboA total of 98 patientswere included

in thepooled analysis(Feagan 2000; Oren 1997). After 36 to 40

weeks of treatment 35 of 40 patients treated with methotrexate

maintained remission compared to 22 of 48 patientstreated with

placebo. Thepooled oddsratio for maintenanceof remission was

3.11 (95% CI 1.31 to 7.41; P= 0.01; SeeFigure2). Thenumber

needed to treat to prevent onerelapsewas4.

Figure 2. Forest plot of comparison: 1 Methotrexate versus Placebo, outcome: 1.1 Proportion of patients

maintaining clinical remission.

6Methotrexate for maintenance of remission in Crohn’sdisease (Review)


Methotrexateversus6-mercaptopurine

A total of 50 patientswereincluded in thepooled analysis(Maté-

Jiménez 2000; Oren 1997). More patientswho wereassigned to

methotrexate(17/22) maintained remission compared to patients

who received 6-MP (16/28). However, this difference was not

statistically significant (OR 2.63; 95% CI 0.74 to 9.37; P= 0.14;

SeeFigure3).

Figure 3. Forest plot of comparison: 2 Methotrexate versus 6-MP, outcome: 2.1 Proportion of patients

maintaining clinical remission.

D I S C U S S I O N

Crohn’sdiseaseisachronic inflammatory diseaseof thegut that is

characterized byperiodsof remission and exacerbations. Oncere-

mission isinduced, patientsoften requirelong-term maintenance

therapy in order to prevent relapse and avoid chronic corticos-

teroid use. Thisgenerally requirestheuseof immunosuppressive

agents(assteroid sparing agents).

Methotrexate, an immunosuppressive, isan effectivedrug for the

treatment of activeCrohn’sdisease(Feagan 1995; Alfadhli 2004).

Accordingly, current practice guidelines recommend the use of

methotrexatefor thispurpose(Lichtenstein 2006).

Threerandomized, controlledstudiesthat investigated theefficacy

of methotrexate for maintenance of remission of Crohn’sdisease

wereidentified for thisreview. Thethreestudiesdiffered signifi-

cantly with respect to methodology. Two studiesinvestigated the

efficacy of methotrexate compared to placebo. Feagan 2000 isa

well-designed trial that establishesmethotrexateasan effectiveand

safedrug for maintenancetherapy in Crohn’sdisease. Thisstudy

had thelargest number of patientsand used intramuscular injec-

tionsof methotrexateat adoseof 15 mgweekly. Thetrial showed

that in Crohn’s patients who had been induced into remission

with methotrexate, significantly morepatientsremained in remis-

sion while taking methotrexatecompared to placebo. Theother

study, Oren 1997, alsocomparedmethotrexatetoplacebo. It used

oral methotrexateat a lower dose(12.5 mg weekly). Theresults

showed no differencebetween patientstreated with methotrexate

or placebo. Thelower doseof methotrexate, oral routeof admin-

istration, and small patient population may havebeen factors in

thelack of benefit seen with methotrexate.

Two studies looked at methotrexate compared to 6-MP. Maté-

Jiménez 2000 is a randomized, controlled trial that used oral

methotrexate 10 mg weekly in patients that had achieved remis-

sion on ahigher dose(15 mgorally weekly). When compared to

patients treated with 6-MP, there was no statistically significant

differencewith respect to maintenance of remission. Oren 1997

also did not show astatistically significant differencebetween the

methotrexateand 6-MPgroups. Both of thesestudiesused alow

doseof oral methotrexateand enrolled small numbersof patients.

Neither of thesestudiesusedapower calculation todeterminehow

many patientsneeded to beenrolled to beableto detect clinically

important differencesbetween study groups.

Maté-Jiménez2000 also investigated oral methotrexatecompared

to 5-ASA. Methotrexatepatientsweresignificantly morelikely to

maintain remission than 5-ASA patients. However only 1 patient

in the5-ASA group participated in themaintenancephaseof the

study. No conclusionscan bedrawn from theseresults

Only1studyexaminedtheeffect of methotrexateonqualityof life.

In Oren 1997, therewasanon-significant trend towardsimprove-

ment in the mean Harvey-Bradshaw index in the methotrexate

group during thefinal 3 monthsof thestudy. Theanalysisof the



Analysis 3.1. Comparison 3 Methotrexate versus 5-ASA, Outcome 1 Proportion of patients maintaining

clinical remission.

Review: Methotrexate for maintenance of remission in Crohn’s disease

Comparison: 3 Methotrexate versus5-ASA

Outcome: 1 Proportion of patientsmaintainingclinical remission

Study or subgroup Methotrexate 5-ASA OddsRatio Weight OddsRatio


Mat -Jim nez 2000 8/12 0/1 100.0 % 5.67 [ 0.19, 169.53 ]

Total (95% CI) 12 1 100.0 % 5.67 [ 0.19, 169.53 ]

Total events: 8 (Methotrexate), 0 (5-ASA)



0.1 0.2 0.5 1 2 5 10

Favours control Favours treatment

W H A T ’ S N E W


Date Event Description

7 July 2009 New citation required and conclusionshavechanged Substantiveamendment

H I S T O R Y

Protocol first published: Issue1, 2008

Review first published: Issue4, 2009

Date Event Description

15 July 2008 Amended Converted to new review format.



Anti-TNF

Efectiva para mantener la remisión

Únicamente se debe administrar por médicos con experiencia en el manejo de la enfermedad de Crohn con biológicos

Excluir infección previo al inicio del tratamiento

Infliximab

• Enfermedad moderada a severa

• Refractaria a 5-ASA, esteroides e inmunosupresores

Enfermedad inflamatoria

Enfermedad fistulizante

Infliximab

Para enfermedad fistulizante iniciar hasta haberse excluido infección

No se recomienda para enfermedad fibroestenótica

Infusión inicial p/2 hrs, subsecuentes en 1 hr

Reiniciar Tx después de un año de suspensión riesgo de reacciones a la infusión

Infliximab

Dosis de carga 5 mg/kg a la semana 0, 2 y 6

Si no hay respuesta a después de 2 dosis, cambiar a adalimumab o a 10 mg/kg

Si hay respuesta, mantenimiento a intervalos de 8 semanas

Disminución de la eficacia, disminuir los intervalos 6 semanas, a 10 mg/kg

Gastroenterol Clin N Am 43 (2014) 457–478

Inducción a la remisión

Adalimumab

Inducción 40/80 mg sc en semanas consecutivas

Mantenimiento 40 mg SC en semanas alternas

Si hay pérdida de respuesta incrementar la administración a semanas consecutivas


Inducción de la remisión

Nutrición

Enteral nutrition for maintenance of remission in Crohn’s

disease (Review)

AkobengAK, ThomasAG

Thisisareprint of aCochranereview, prepared andmaintained byTheCochraneCollaboration and published in TheCochraneLibrary

2009, Issue3


Enteral nutrition for maintenance of remission in Crohn’sdisease (Review)


Analysis 2.1. Comparison 2 Elemental formula supplements versus no supplementation, Outcome 1

Relapse.

Review: Enteral nutrition for maintenance of remission in Crohn’sdisease

Comparison: 2 Elemental formula supplementsversusno supplementation

Outcome: 1 Relapse

Study or subgroup Supplements No supplements OddsRatio Weight OddsRatio


Takagi 2006 9/26 16/25 100.0 % 0.30 [ 0.09, 0.94 ]

Total (95% CI) 26 25 100.0 % 0.30 [ 0.09, 0.94 ]

Total events: 9 (Supplements), 16 (No supplements)



0.1 0.2 0.5 1 2 5 10

Favours supplements Favours no supplemen

W H A T ’ S N E W


27 May 2008 Amended Converted to new review format.

H I S T O R Y

Protocol first published: Issue2, 2006

Review first published: Issue3, 2007

30 April 2007 New citation required and conclusionshavechanged Substantiveamendment

D E C L A R A T I O N S O F I N T E R E S T

Dr Akobengand Dr Thomashaveboth received financial support from SHSInternational for induction studiesof enteral nutrition in

children with Crohn’sdisease.

12Enteral nutrition for maintenance of remission in Crohn’sdisease (Review)






2009, Issue1




LocalizaciónEnfermedad ileal e ileocólica

En base a la severidad de la enfermedad

Enfermedad moderada

Esteroides orales 20-40 mg prednisona, budesonida9 mg (enfermedad ileocecal)

Anti-TNF enfermedad refractaria (inducción y mantenimiento)

Considerar cirugía temprana

Riesgo acumulado de desarrollar fístula perianal

10% a 1 año

15% a 5 años

20% a 10 años

Presencia de fístula

12 % en enfermedad ileal

15% en ileocólica

41% colónica

92% rectal

LocalizaciónPerianal

Descartar la presencia de sepsis perianal

Tratamiento quirúrgico

Extensión de la enfermedad (IRM, ultrasonido)

Metronidazol 400 mg c/8 hrs, con o sin ciprofloxacino 500 mg C/12 hrs

AZA 2-2.5 mg/kg/dia o MP 0.75-1.5 mg/kg/día

Anti-TNF enfermedad severa perianal, fístula enterocutánea refractaria

LocalizaciónPerianal

LocalizaciónEnfermedad fistulizante no perianal

Fistula entero-cutánea, fístula entero-enteral, fístula entero-visceral (vejiga, vagina)

No existen estudios aleatorizados controlados para la enfermedad fistulizante

Fístulas sintomáticas requieren tratamiento quirúrgico

LocalizaciónOtros sitios

• Esteroides tópicos, tacrolimus tópico, inyección intra-lesional de esteroides, dieta de exclusión, nutrición enteral, infliximab

Enfermedad oral

• Peor pronóstico

• Adición de IBP, reportes de caso Tx con anti-TNF

Enfermedad gastro-duodenal

Enfermedad leve a moderada

Sin tabaquismoPresentación inicial leveNo enfermedad perianal

No manifestaciones gastrointestinales

Cesar tabaquismoSulfasalazina y/o antibióticos

Cesar tabaquismoBudesonida/corticoesteroides

Continuar y observar

Disminuir, suspender y observar

Azatioprina o MTX

Azatioprina o MTX

Agregar anti TNFDetener Aza/MTX

A los 6 meses

Enfermedad colónica Enfermedad en intestino delgado

Respuesta No respuesta

Respuesta No respuesta

Recaída en el 1er año

Recaída

Enfermedad ileal, ileocólonica, colónica:

Mesalazina 3.2 a 4 g/día

Ileocolónica o colónica:

Sulfasalazina 3 – 6 g

Evidencia:

• Mínimamente efectiva vs placebo

• Menos efectiva que esteroides y que budesonida

Colon derecho o ileon Budesonida 9mg/día

Terapia antituberculosa no es efectiva

1/3 logra remisión a las 16 semanas con sulfasalazina

Mesalazina 3.2 – 4 g mostró diferencia significativamente vs placebo, pero sin relevancia clínica (beneficio de CDAI 18 puntos)

¿Antibióticos?

Hipótesis causa o factor exacerbante

Metronidazol 10 – 20mg/kg vs placebo

Metronidazol ileocolitis y colitis

Metronidazol vs sulfasalazina – cruzado pacientes que fallaron a uno, respondieron al otro

Ciprofloxacino vs Mesalazina 50% alcanzaron remisión clínica

Ciprofloxacino +Metronidazol + budesonida (9mg/d) tendencia en enfermedad colónica

Rifaximina 200 c/12hrs no superioridad vs placebo

Budesonida oral 9mg c/24hrs > mesalazina o placebo

Semejante a otros esteroides orales en ileon distal y/o colon derecho

Budesonida ha mostrado ser el mejor tratamiento con eficacia a corto plazo y mejor perfil de seguridad

Budesonida es la opción preferida como terapia primaria en pacientes con

enfermedad leve a moderada que tienen enfermedad localizada en ileon y/o colon

derecho

El manejo en EC en tracto GI superior:

IBP

Costico-esteroides sistémicos

Azatioprina

6 mercaptopurina

Metotrexato

Infliximab

Adalimumab

Certolizumab pegol

Enfermedad moderada a severa

Sin tabaquismoEdad de presentación >18 años

Enfermedad extensaEnfermedad perianal

Manifestaciones extraintestinales

Cesar tabaquismoAzatioprina / MTX y anti TNF

Continuar y observar

¿Cirugía?Drogas experimentales

Prednisona 40-60mg/d hasta resolución de síntomas o reinicio de ganancia de peso (7-28 días)

Azatioprina y 6 MP para mantener la remisión inducida por esteroides

Metotrexato parenteral 25mg/semana para EC dependiente de esteroides o refractaria a esteroides

Anti TNF:

Infliximab, adalimumab, certolizumab pegol

Pacientes que no respondieron a terapia con corticoesteroides o inmunosupresores

Infliximab e Infliximab + azatioprina son más efectivos que la azatioprina en pacientes que fallaron a terapia de primera línea

Infliximab, adalimumab, certolizumab pegolalternativas a la terapia con esteroides en pacientes con contraindicación

Tx con corticoesteroides

50 a 70% alcanzan remisión a las 8 a 17 semanas

Prednisona 0.5 – 0.75 mg/kg (40mg)/ día

80 – 90% alcanzan respuesta

Prednisona 1mg/kg o metilprednisona 1mg/kg

Estrategias

STEP UP VS TOP DOWN

Aloi, M. et al. (2013) Nat. Rev. Gastroenterol. Hepatol

Best Practice & Research Clinical Gastroenterology 28 (2014) 473–483

Lancet 2008; 371: 660–67

Tratamiento quirúrgico

Indicaciones de cirugía

Surgery. 2008: 26(8): 352-356

Indicaciones de cirugía electiva

① Cáncer por E. Crohn

② Incapacidad para superar síntomas

③ Complicaciones relacionadas a medicamentos

④ Mal apego a tratamiento médico

J Korean Soc Coloproctol 2012;28(3):121-131

JAMA. 2013;309(20):2150-2158

Predictores de cirugía

Eur J Gastroenterol Hepatol 2013, 25:129–134

Am J Gastroenterol 2003;98:2712- 2718

Cirugía temprana significativamente más frecuente en pacientes con enfermedad ileal localizada

Dolor abdominal fue el síntoma más frecuente que se presentó previo a la cirugía

Am J Gastroenterol 2012; 107:1693–1701

Tratamiento crohn

Health & Medicine

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