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Treatment of Treatment of Mild to moderate Mild to moderate
Extensive Extensive Ulcerative ColitisUlcerative Colitis
Philippe Marteau, Paris, FrancePhilippe Marteau, Paris, France
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Mild to moderate Extensive UCMild to moderate Extensive UC
Oral ASA are needed as local treatments cannot cover all lesions
Recommendation : 1st line : oral 5-ASA 4 g/dObtaining endoscopic remission or frank improvement
usually takes more than 4 weeks
2nd line : if severe or resistant : consider oral steroids
Marteau P et al. Gastroenterol Clin Biol. 2004 Oct;28(10 Pt 2):955-60.
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UC Consensus 2006UC Consensus 2006Treatment of Active DiseaseTreatment of Active Disease
Simon Travis, Eduard Stange, Simon Travis, Eduard Stange, Yehuda Chowers, Philippe Yehuda Chowers, Philippe MarteauMarteau
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Active disease Active disease ECCO Statement: Extensive colitisECCO Statement: Extensive colitis
● Extensive ulcerative colitis of mild-moderate severity should initially be treated with mesalazine >2g/day [EL1a, RG A], combined with topical mesalazine[EL1b, RG A]
● Oral aminosalicylates alone induce remission only in a minority of patients [EL1a, RG A]….
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Optimise the first line treatment of extensive UC ?
– Many symptoms originate form the distal colon
(blood in stools, tenesmus…)
– Is association of local and oral salicylates better than
oral treatment alone ?
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PatientsPatients
● 116 patients
● Mild to moderate exacerbation of extensive UC (UCDAI ≥3 and ≤8)
● Exclusion criteria: ● maintenance treatt with aminosalicylates > 3 g/d● corticosteroids● immunosuppressive agents
Marteau et al. Gut 2005;54:960-5
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MethodsMethods
● Double-blind, parallel-group, placebo-controlled RCT
● For 8 weeks, each patient received 4 g/d pentasa orally
● During the initial 4 weeks, each patient additionally applied daily a 100 mL enema at bedtime, either containing 1 g Pentasa or placebo
● Evaluation ● at inclusion, 4 weeks and 8 weeks ● UCDAI score (clinical signs and endoscopic evaluation of
the distal colon)
Marteau et al. Gut 2005;54:960-5
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0102030405060708090
100
Rem. Imp. Rem. Imp.
week 4 week 8
%
P=0.308
P=0.0008
P=0.030
P=0.026
Pentasa orally + pentasa enema
Pentasa orally + placebo enema
Marteau et al. Gut 2005;54:960-5
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Time to cessation of rectal bleeding Time to cessation of rectal bleeding Patients with frank bleeding at baselinePatients with frank bleeding at baseline
Marteau et al. Gut 2005;54:960-5
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Active disease Active disease ECCO Statement: Extensive colitis (cont)ECCO Statement: Extensive colitis (cont)
Systemic corticosteroids are appropriate if symptoms of active colitis do not respond rapidly to mesalazine [EL1b, RG C],
or for patients who are already taking appropriate maintenance therapy
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Active disease Active disease ECCO Statement: ECCO Statement: Oral steroidOral steroid--refractory UCrefractory UC
● Patients with persistently active, steroid-refractory disease should be treated with azathioprine / mercaptopurine [EL1b, RG B], – Although surgical options should also be discussed – intravenous steroids, – infliximab [EL1b, RG B] – or calcineurin inhibitors [EL3, RG C]
should also be considered
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Active disease Active disease ECCO Statement: ECCO Statement: ThiopurineThiopurine--intolerant or intolerant or --refractory ulcerative colitisrefractory ulcerative colitis
● Infliximab [EL1b, RG B] or surgical options should be considered
● Continued medical therapy that does not achieve steroid-free remission is not recommended [EL5, RG D]
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Infliximab in Ulcerative colitis ACT1 & ACT2 Rutgeerts et al. N Engl J Med 2005;353:2462-76
●● 2 RCTs 364 patients in each
● Patients with active UC (extensive 40% - 46%):– Mayo score of 6 to 12 points - Endoscopic subscore ≥2
●Either– Concurrent treatment with ≥ 1 of the following:
– Steroids, azathioprine, 6-MP, or aminosalicylates (ACT 2 only)– Failure to tolerate or respond to ≥ 1 of:
– Steroids, azathioprine, 6-MP, or aminosalicylates (ACT 2 only)
● Infliximab 5mg/kg vs 10mg/kg vs placeboAt weeks. 0,2,6 then every 8 weeks. 46 weeks
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ACT 1 ACT 1 Rutgeerts et al. N Engl J Med 2005;353:2462-76
38,8
33,932
36,9
14,9 15,7
05
1015202530354045
8 Weeks 30 Weeks
Perc
ent o
f Pat
ient
s
IFX 5 mg/kgIFX 10 mg/kgPlacebo
‡
††
† 62
50,4
59
49,2
33,9
24,8
0
10
20
30
40
50
60
70
8 Weeks 30 Weeks
Perc
ent o
f Pat
ient
s
IFX 5 mg/kgIFX 10 mg/kgPlacebo
††
† †
21,7
10,1
0
5
10
15
20
25
CorticosteroidDiscontinued (Week 30)
Perc
ent o
f Pat
ient
s
IFX (combined)Placebo
†
Clinical RemissionClinical Remission EndoscopicEndoscopic RemissionRemission
Steroid discontinuationSteroid discontinuation
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Infliximab (keep thiopurines) or calcineurine inhib.
AlgorithmAlgorithmOral 5-ASA (4g/d)
Oral 5-ASA (4g/d) + 5-ASA enema (or suppos?)
Oral steroids (40-60mg/d) (keep 5-ASA ?)
Tapering ... consider thiopurines (keep 5-ASA !)
Surgery
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Infliximab (keep thiopurines) or calcineurine inhib.
AlgorithmAlgorithmOral 5-ASA (4g/d)
Oral 5-ASA (4g/d) + 5-ASA enema (or suppos?)
Oral steroids (40-60mg/d) (keep 5-ASA ?)
Tapering ... consider thiopurines (keep 5-ASA !)
Surgery
What happened before ?How many episodes ?Resistance to treatments ?
Severity ?Patient preferences ?Personal view on the risk/benefit
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Infliximab (keep thiopurines) or calcineurine inhib.
AlgorithmAlgorithmOral 5-ASA (4g/d)
Oral 5-ASA (4g/d) + 5-ASA enema (or suppos?)
Oral steroids (40-60mg/d) (keep 5-ASA ?)
Tapering ... consider thiopurines (keep 5-ASA !)
Surgery
What happened before ?How many episodes ?Resistance to treatments ?
Severity ?Patient preferences ?Personal view on the risk/benefit
Directly ? No improvement
after 2 weeks
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Infliximab (keep thiopurines) or calcineurine inhib.
AlgorithmAlgorithmOral 5-ASA (4g/d)
Oral 5-ASA (4g/d) + 5-ASA enema (or suppos?)
Oral steroids (40-60mg/d) (keep 5-ASA ?)
Tapering ... consider thiopurines (keep 5-ASA !)
Surgery
What happened before ?How many episodes ?Resistance to treatments ?
Severity ?Patient preferences ?Personal view on the risk/benefit
Directly ?
If previous failure to 5-ASA
If « rapid remissionneeded » ?
If nocturnal stools ?
No improvementafter 2 weeks
4-8 weeks
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Infliximab (keep thiopurines) or calcineurine inhib.
AlgorithmAlgorithmOral 5-ASA (4g/d)
Oral 5-ASA (4g/d) + 5-ASA enema (or suppos?)
Oral steroids (40-60mg/d) (keep 5-ASA ?)
Tapering ... consider thiopurines (keep 5-ASA !)
Surgery
What happened before ?How many episodes ?Resistance to treatments ?
Severity ?Patient preferences ?Personal view on the risk/benefit
Directly ?
If previous failure to 5-ASA
If « rapid remissionneeded » ?
If nocturnal stools ?
If steroid dependencyor contra-indication
& thiopurine resistance
No improvementafter 2 weeks
4-8 weeks
4 weeks
4 - **** weeks