medical management of ulcerative colitis€¦ · medical management of ulcerative colitis gerhard...

University HospitalZurich

U

Medical management of ulcerative colitis

Gerhard Rogler, Zürich

18.05.2009 / 2


UStep up approach to therapy of Ulcerative colitisStep up approach to therapy of Ulcerative colitis

SurgerySurgeryCyclosporineCyclosporineTacrolimusTacrolimusInfliximabInfliximab

AZA/6AZA/6--MP MP Corticosteroids Corticosteroids

(topical/systemic)(topical/systemic)

AminosalicylatesAminosalicylates(topical/systemic)(topical/systemic)

Seve

re

Mod

erat

e

Mild

18.05.2009 / 3


U

SASP 5-ASA top. SASP/ASAPrednisolone

Steroid Enema0

20

40

60

80

100% Success

Drug

Placebo

TA

39%TA

41%

TA

56%TA

56%TA

41%

MetaMeta--analysis of drug analysis of drug treatment treatment

of ulcerative colitisof ulcerative colitis

Kornbluth, 1993

18.05.2009 / 4


UCase 1: Musician with proctosigmoiditis

Started 5-ASA enemas with initial successSwitched to oral 5-ASA 2.4 g for flareSteroids 40 mg/day for subsequent flares still has 8 BM/day, malaise without fever. Works but wants to feel good.

What next ???

18.05.2009 / 5


U

Treatment Success at Weeks 3 & 6Pooled Moderate Population

58%53%

72%62%

0%10%20%30%40%50%60%70%80%

Week 3 Week 6

% o

f Pat

ient

s Im

prov

ed

2.4 g/day4.8 g/day

5-ASA: More is Better

p=0.0034p=0.058

N=223 N=223N=198 N=200

*

ASCEND I, II

Hanauer et al. Am J Gastroenterol 2005

18.05.2009 / 6


UDose finding for 5-ASA in active ulcerative colitis

Kruis et al., Clin Gastroenterol Hepatol 2003

8 weeks 3 x 0.5 g 3 x 1.0 g 3 x 1.5 g(n = 104) (n = 104) (n = 104)

Remission (CAI < 4) 50 66 * 55

Time to response 27.5 26.5 21.6(days, mean)

Endoscopic remission (%) 28 48 * 49

Histological improvement (%) 42 56 * 63

Stop due to side effects (n) 11 7 9

18.05.2009 / 7


U

5-ASA topical therapyis preferable

% R

emis

sion

% R

emis

sion

MonthsMonths

D’Albasio. Am J Gastroenterol 1997

4 g QOD enema4 g QOD enema

1.6 g/day oral1.6 g/day oral

00

2020

4040

6060

8080

100100

120120

22 44 66 88 1010 1212 1414 1616 1818 2020 2222 2424

18.05.2009 / 8


U

5-ASA: Combination is better

Safdi. Am J Gastroenterol 1997

% R

espo

nse

% R

espo

nse

00

1010

2020

3030

4040

5050

6060

7070

8080

9090

100100

1 week1 week 2 weeks2 weeks 3 weeks3 weeks 6 weeks6 weeks

Oral Oral

RectalRectal

CombinedCombined

18.05.2009 / 9


UCorticosteroids: Short and Long Term Efficacy

*30 days after initiating corticosteroid therapy Faubion W, et al. Gastroenterology. 2001;121:255.

1-Month Outcomes*(n=63)

1-YearOutcomes(n=63)

Steroid Dependent

22%(n=14)

Prolonged Response

49%(n=31)

Surgery 29%

(n=18)

Complete Remission

54%(n=34)

Partial Remission

30%(n=19)

No Response

16%(n=10)

18.05.2009 / 10


U

Days

% C

umul

ativ

e Pr

obab

ility

0

20

40

60

80

100

0 30 60 90 182 365

Risk of Resection in UC After 1st Course of Steroids:

Faubion WA Jr, et al. Gastroenterology. 2001;121:255.

*185 patients in Olmsted County, MN diagnosed with UC from 1970 to 1993

18.05.2009 / 11


U

05

10152025303540

ACT 1 ACT 2

PlaceboInflix. 5 mg/kgInflix. 10 mg/kg

remission after 8 weeks (%)

Infliximab 5 mg/kg or 10 mg/kg in ACT 1 and 2 significantly better than placebo

Infliximab for the induction of remission in active ulcerative colitis

Rutgeerts et al. NEJM 2005;353:2462-76

14.9

38.8

32.0

5.7

33.9

27.5

p < 0.001 p < 0.001

p = 0.002 p < 0.001

18.05.2009 / 12


U

%%

0

5

10

15

20

25

30

Week 30

21,7%

10,1%

Patients without steroids

Infliximab for the induction of remission in active ulcerative colitis

Rutgeerts et al. NEJM 2005;353:2462-76

18.05.2009 / 13


UCase 2: Actor with refractory pan-colitis

Formerly in remission on AZA 10-20 BM/dayProgressive weight lossTransferred by air ambulanceIV steroids, PRBC, TPN

18.05.2009 / 14


UDoes anti-viral therapy help?

64 non-refractory IBD pts ( UC 23:CD 43) 1• 42 (66%) had + serology• 1 had CMV Ag and biopsy-proven CMV colitis

• only this patient had benefit

47 inpatients with UC checked for CMV Ag in blood2

• 12/16 UC pts with +CMV treated • 8 (66.7 %) responded62 pts with severe colitis (55 UC;7 CD)3

• 7 (5UC,2 CD) out of 19 (36%) pts with refractory disease: CMV found in rectal bx

• 5/6 treated patients went into remission after antiviral treatment; 1 did not->surgery

1) de Saussure P. APT 2004;20;13232) Wada Y Dis Col Rect. 2003 ;46(10):S59-65.3) Cottone M. AJG. 2001. 96(3):773-5.

18.05.2009 / 15


UCurrent therapeutic choices in severe UC

CyA/TacrolimusInfliximabClinical TrialColectomy

Choice will depend on center expertise with drug choices and availability of expert surgical support

Arseneau K. Clin Gastro Hep 2006. 4(9);1135-1142

18.05.2009 / 16


U5-ASA orally for relapse prevention in

ulcerative colitis

Miner, 1995

5-ASA Placebo(n = 103) (n = 102)

Remission at 12 months (%) 64 38

Left sided (%) 63 41

Extensive colitis (%) 67 31

18.05.2009 / 17


U

Acute flarewithin 12 months

36 % E. Coli Nissle

E.coli Nissle E.coli Nissle in UCin UC

E. coli Nissle(Mutaflor)200 mg

222 patients

33 % 5-ASA

5-ASA 1.5 g

Kruis et al, GUT, Nov 2004

18.05.2009 / 18


U

OR

Continous 5-ASA intake 0.25 (0.13 - 0.48)*

Continously 5-ASA > 1.2 g/day 0.19 (0.05 - 0.61)*< 1.2 g/day 0.18 (0.02 - 1.92)

SASP 2g/day 0.85 (0.32 - 2.26)

Regular visit to physician (> 2/year) 0.16 (0.04 - 0.60)*

Number of colonoscopies after diagnosis no effect

Positive family history 5.0 (1.10 - 22.82)**

* p < 0.01 ** p < 0.04

Carcinoma prevention in UC: Role of 5-ASA

Eaden, 2000

18.05.2009 / 19


U

Compliance is crucial!!

Kane et al, Am J Med, 2003

18.05.2009 / 20


U

Final Points

There is no “one size fits all” to UC therapy• Therapy and decision making are tailored to the individual

Mild to moderate disease:• Remember topical therapy

Success of algorithms depends upon optimization of each step of therapy and considerable judgment about each outcome

• Skillful application of medical therapy makes the difference in outcomes: topical therapy, combination of oral and rectal administration, appropriate dosage

18.05.2009 / 21


U

Thank you for your attention!!

medical management of ulcerative colitis€¦ · medical management of ulcerative colitis gerhard...

Documents