management of ibd -15 march y mikhail

8/2/2019 Management of Ibd -15 March y Mikhail

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Dr. WAGDY E. MIKHAL

GastroenterologistInternational Modern Hospital

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Crohn`s Disease (CD ) &Ulcerative Colitis (UC)arechronic inflammatory bowel disease of unknownetiology.

They follow a chronic course characterized by frequent

relapses with phases of remission followed by moreacute episodes.

Some patients have activity of different degree alwayspresent. CD & UC are progressive Disease

The immunological factors which are responsible forthe different types of disease behavior are unclear &the reason for relapse is unknown.

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Induction of remission.

Maintenance of remission.

Healing of intestinal mucosa.(Deep Mucosal Healing)

Prevention of associated complications. Restoration & maintenance of nutrition.

Improve quality of life of Patient.

Selection of optimal timing for those patients requiring

surgical intervention. STOP Disease Progression & Prevent or Reduce

Bowel Damage *Treat beyond Symptoms*.

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4

Mortality (


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Recurrence at the Anastomotic site.

Sepsis

Anastomotic Leak

Peritonitis Anastomotic Stricture

Might require repeat Surgery

berra FN, Lewis JD, Hass D, Rombeau JL, Osborne B, Lichtenstein GR. Corticosteroids and immunomodulators:

Postoperative infectious complication risk in inflammatory bowel disease patients. Gastroenterology. 2003;125:3207

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Complications & Side Effects of Medicaltreatment


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Dose-related (10-45%)

- headache, nausea, epigastric pain, diarrhoea*

Idiosyncratic (rare)

- acute pancreatitis; hepatitis; myocarditis;pericarditis; eosinophilia; fibrosing alveolitis;interstitial nephritis; nephrotic syndrome

- peripheral neuropathy- blood disorders

- skin reactions lupus like syndrome; Stevens-

Johnson syndrome; alopecia


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immune-complexmediatedhypersensitivity

erythemamultiforme

target lesions,

mucosalinvolvement


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Heinz body anaemia; Megaloblastic anaemia

Hypersensitivity reactions

Orbital oedema

Renal reactions

Neurological reactions

Oligospermia

Orange coloured urine & tears


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Downloaded from: StudentConsult (on 24 October 2005 02:39 PM)

2005 Elsevier

Side effects of Steroids


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Flu-like symptoms (20%)

- occur at 2-3 weeks; cease on withdrawal

Hepatotoxicity; pancreatitis (


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Infusion reactions/anaphylaxis;

Infection (TB reactivation; overwhelming sepsis)

Reactivation of Hepatitis B

Rare reports of lymphoma and cancer . Fatal blood disorders

Severe Allergic Reaction.

Antibody formation SLE like illness

Worsening of Congestive Heart Failure Multiple Sclerosis, seizures, inflammation of the ocular

nerve

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Ms.RAI 14 ys old Egyptian student.

Diagnosed as Crohn`s disease (CD) in Jan 2011 by CT scan ,Colonoscopy& Biopsy ;after 1 year H/O diarrhea &Abd.pain

On 31/01/2011 Presented with abd pain, Loose motions,

Hb 11.1 gm/dl Hct 38

CRP 85 mg/L

Alb. 3.2 gm/dl

CDAI 293

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Thickened wall of different segment ileal loops mainly at Rt .Iliac fossa with

Post-contrast enhancement & consequent proximal dilatation of small intestine

Suggestive of IBD ,Crohn`s Disease. 14


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Management on 31rd Jan.2011:

Prednisolone 30 mg OD ; Tapering Dose

Pentasa 500 mg TID

Metronidazloe 200 mg TID

Improved with less frequent stools Abd.pain subsided

When Prednisolone does reduced to 20 mg /day, patienthad severe Abd.pain ,loose motions & vomting

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Admission to Rashid Hospital on 19th Feb.2011

Sudden severe lower Abd.pain with loose motions 5/day

No fever ,No Joint pain or Eye symptoms.

ON Ex

Afebrile BP 105/60 P.128/min Looked sick & in Pain 8/10

Abdomen :Generalized tenderness, more at RT.IF

Bowel sounds very scanty, Rebound ve

PR Tenderness & indurations RT side

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FBC : WBC 20.2 Hgb 9.0 gm/dl Plt. 586,000 /cc

CRP : 150 MG/L Hct 37

CDAI 406

ESR : 48 mm/hr

K :2.9 MMOL/L LFT :Normal except for Alb.3.1g/dl

TFT,RFT within Normal

HIV Ab,HCV Ab & HBsAg all Neg.

Work up for TB Negative Stool : Loose, with mucus, No OB,WBC 3+ No Ova or Parasite

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Signicant pelvi-Abd free fluid mainly at the Pelvis.

Multiple mesenteric L.N .

Dilated loops involving the Jejunum & Ascending

Colon. No Free Air

Both kidneys were small non-obstructive calculi seenin Lt.Kidney

Liver,GB,Pancrease&speen were unremarkable.

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On 27th March2011:

1st Induction dose of Infliximab

During induction & Maintenance therapy ,shedeveloped 2 attacks of Flare up needed 2 coursesof tapering Steroid..

Latest Maintenance dose given on 8TH Feb.2012

What to do next ?????????????????????? Surgery ??

Azathioprine ??

Shift biologic therapy ??

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Delayed Diagnosis ,after 1year of symptoms.

Predictors of disabling disease not considered

Plan of Management was not clear .

Steroid dosing ? Suboptimal.

Surgical referral & opinion delayed.

What was the Goal of management??

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Severe

Moderate

Mild

Adapted from: Hanauer et al, Am J Gastroenterol 2001; 96: 635

Budesonide

Antibiotics

5-ASA

MTX

AZA / 6-MP

Systemic steroids

Surgery

anti-TNF-

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Chimericmonoclonal antibody

Humanrecombinant antibody

HumanizedFab

fragment

Infliximab Adalimumab

Certolizumab

pegol

PEG

PEG

VHVL

CH1NoFc

IgG1 IgG1

Mouse

Human

PEG = Polyethylene glycol


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Anti TNF

AZA/MTX

Steroids

5-ASA/SPS

Anti TNF

AZA/MTX

Steroids

Combination

Step-up

therapy

Top-down

therapy

Lichtenstein GR et al. Inflamm Bowel Dis. 2004;10:S2S10.26


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1-Ricart E et alWorld J Gastro,2008;14:5523-5527

2-Constnes J et al,Gut;2005;54:237-241.

3-Louice E.Gut 2001 ;49:777-782.4-Constnes J et al ;2002; 8 :244-250 28


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D`Haens G.et.al.Lancet 2008;371 :660-667 29

SONIC


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Week 0*

Week 2

Week 6

Week 14

Week 22

Week 30

Visits

Week 46

Week 38

Week 54

Infusions

Primary End Point (Corticosteroid-free Remission at Week 26)

Secondary End Point (Week 50)

Main

Extension

Week 26*

Week 50

Randomisation of patients

Azathioprine 2.5 mg/kg+ placebo infusions

Infliximab 5 mg/kg+ placebo capsules

Infliximab 5 mg/kg+ azathioprine

2.5 mg/kg

* Endoscopy performed at weeks 0 and 26.

Week 10

Week 18

Week 42

SONIC

30

170 169169

SONIC


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Primary End Point

30.6

44.4

56.8

0

20

40

60

80

100

Propo

rtionofPatients(%)

AZA + placebo IFX + Placebo IFX+ AZA

P


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17

30

44

0

20

40

60

80

100

Pro

portionofPatients(%)

AZA + Placebo IFX + Placebo IFX + AZA

P


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BG Feagan et al. Effects of Adalimumab Therapy on Incidence of Hospitalization and Surgery in Crohns Disease: Results From the CHARM Study.

Gastroenterology. 2008;135:14931499

0

0.5

1

1.5

2

2.5

3

3.5

4

4.5

EOW (n=260) EW (n=257) Combined (n=517) Placebo (n=261)

0.4

0.80.6

4.2

90% reduction

86% reduction

CHARM

Surgeryrate

(Nsurgeryp

erN

patie

nts)

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CHARM: Treatment with adalimumab significantly decreased the risk of both all-causeand CD-related hospitalization in all comer patients

BG Feagan et al. Effects of Adalimumab Therapy on Incidence of Hospitalization and Surgery in Crohns Disease: Results From the CHARM Study.

Gastroenterology. 2008;135:14931499

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Results: N=29 pts

>50% had previous IFX treatment Mean 1.76 resections prior to ADA

administration

Recurrence rates at 12 months: Biological: 7/29 pts (24.1%) Endoscopic: 6/29 pts (20.7%) Radiographic: 7/19 pts (36.8%)

There was good correlation betweenbiologic-endoscopic, biologic-radiologic, and endoscopic-radiologicrecurrences (p


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P = 0.015P = 0.001

32%Reduction

48%

Reduction

There would be 25

hospitalizations if 100 patients

are followed for 1 year

N = 83

TAR = 401

N = 69

TAR = 224N = 54

TAR = 401N = 57

TAR = 224

Feagan B, et al. UEGW2011:OP

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N = 53 N = 51

TAR = 385 TAR = 215

N = 63 N = 61

TAR = 401 TAR = 224

P = 0.005 P = 0.002

42%

Reduction

41%

Reduction

TAR, time at risk (in person years).


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N = 14 N = 10

TAR = 399 TAR = 224

P = 0.56

4.5 patients would requirecolectomy if 100 patients are

followed for 1 year

22%

Reduction

TAR, time at risk (in person years).


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Vermiere et al, Aliment Pharmacol Ther 2006; 25: 3

Response

Continue Txand observe

Response

Taper & stop TxObservation

Relapse within 1yr?

Steroids + AZAor MTX

No response

AZA or MTX? Surgery

Relapse

Anti-TNF-No response

Noresponse

Colonic

( small intestine) Small intestine

Smoking cessationSulfasalazine antibiotics

Smoking cessationBudesonide / corticosteroids

Patient Mild presentation Inflammatory disease No perianal disease No extraintestinal manifestations Non-smoking

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Adapted from Vermiere et al, Aliment Pharmacol Ther 2006; 25: 3

Patient Young age at onset (


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Goals of therapy have shifted to Complete steroid-free remission

Complete Mucosal Healing

(Best achieved by Biologic & associated with long termoutcomes)

To prevent Hospitalization & Avoid or Delay surgery

Identify patients with poor prognosis to act

early. Monitor patients regularly using objective

markers to avoid complications.

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Preliminary studies have provided someevidence that reversing the treatment paradigmfrom a "step up" to a "top down" approach

may positively alter the natural history of CD

Evidence suggests that early use of biologictherapy is effective in improving quality-of-life

and helping patients to achieve and maintainremission

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Management of IBD is Multidisciplinary withGastroenterologist,Surgeon,Dietitian,IBDTrained Nurse, Together with the Patient &

Family

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Step up

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TOP DOWN


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management of ibd -15 march y mikhail

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