Inflammatory Bowel Disease Inflammatory Bowel Disease (IBD)(IBD)

Dr. Noor AbonewairDr. Noor Abonewair

MBBCh, MSc, MRCP (UK) MBBCh, MSc, MRCP (UK) Consultant Physician & GastroenterologistConsultant Physician & Gastroenterologist

From May 2000 to May 2007From May 2000 to May 2007

460 colonoscopy were done at RNH 460 colonoscopy were done at RNH endoscopy unit, Riyadhendoscopy unit, Riyadh

FINDINGS:FINDINGS:UC rectum and rectosigmoid 64 patients (14%)UC rectum and rectosigmoid 64 patients (14%)UC rectosig + left colon 50 patients (11%)UC rectosig + left colon 50 patients (11%)Total ulcerative colitis 27 patients (6%)Total ulcerative colitis 27 patients (6%)Non-specific colitis 23 patients (5%)Non-specific colitis 23 patients (5%)Diverticular disease 23 patients (5%)Diverticular disease 23 patients (5%)Polyps 27 patients (6%)Polyps 27 patients (6%)Carcinoma 14 patients (3%)Carcinoma 14 patients (3%)Crohn’s disease 3 patient (0.5%)Crohn’s disease 3 patient (0.5%)Rectal ulcer 5 patients (1%)Rectal ulcer 5 patients (1%)Telangiectasia 3 patient (0.5%)Telangiectasia 3 patient (0.5%)Normal 221 patients (48%) Normal 221 patients (48%)

So, UC was the finding in 141 (31%) patients, So, UC was the finding in 141 (31%) patients, 110 males and 31 females110 males and 31 females

Crohn’s disease, in only 3 patientsCrohn’s disease, in only 3 patients

Age varies from 14 to 57 years, mostly between Age varies from 14 to 57 years, mostly between 15 and 40 years15 and 40 years

6 patients with severe total colitis were referred 6 patients with severe total colitis were referred for surgery due to failure of response to therapy for surgery due to failure of response to therapy

The distribution of involvement of The distribution of involvement of colon in our UC patients was:colon in our UC patients was:

* Limited to rectum and rectosigmoid in * Limited to rectum and rectosigmoid in 45%.45%.

* Beyond the sigmoid but not the whole * Beyond the sigmoid but not the whole colon in 36%.colon in 36%.

* Total colitis in 19%* Total colitis in 19%

INFLAMMATORY BOWEL INFLAMMATORY BOWEL DISEASE (IBD)DISEASE (IBD)

DEFINITIONDEFINITION::IBD includes ulcerative colitis (UC) and Crohn’s IBD includes ulcerative colitis (UC) and Crohn’s

disease (CD)disease (CD)

EPIDEMIOLOGY:EPIDEMIOLOGY:Whites > blacks or AsiansWhites > blacks or AsiansJews have incidence 3-6 times greater>non-JewsJews have incidence 3-6 times greater>non-JewsSexes are affected equallySexes are affected equallyUC is the more common UC is the more common > CD> CD

In western Europe and the US, IBD occurs most In western Europe and the US, IBD occurs most frequently in people in their late teens and twenties. frequently in people in their late teens and twenties. There have been cases in children as young as two There have been cases in children as young as two years old and in older adults in their seventies and years old and in older adults in their seventies and eighties. Men and women have an equal chance of eighties. Men and women have an equal chance of getting the disease.getting the disease.

UCUC CDCD

IncidenceIncidence 11/100,00011/100,000 7/100,0007/100,000

PrevalencePrevalence 90-170/100,00090-170/100,000 50-70/100,00050-70/100,000

In Asia and South America, IBD is rare; incidence In Asia and South America, IBD is rare; incidence rates of UC and CD are 0.5 and 0.08/100,000, rates of UC and CD are 0.5 and 0.08/100,000, respectively( 1 in200,000 and 1 in one million)respectively( 1 in200,000 and 1 in one million)

UC is twice as common in non-smokersUC is twice as common in non-smokers

In contrast, smoking doubles the risk for CDIn contrast, smoking doubles the risk for CD

Oral contraceptives also doubles the risk for CDOral contraceptives also doubles the risk for CD

What Causes IBD?What Causes IBD?

The cause (s) of IBD are not known, but there The cause (s) of IBD are not known, but there are several theories. One theory is based on are several theories. One theory is based on genetics indicating that IBD does run in genetics indicating that IBD does run in families. About 15–30% of patients with IBD families. About 15–30% of patients with IBD have a relative with the disease. There is a have a relative with the disease. There is a research going on to find out if a specific gene research going on to find out if a specific gene or a group of genes makes a person more or a group of genes makes a person more susceptible to getting the disease.susceptible to getting the disease.

@ Exogenous factors@ Exogenous factors* * M.paratuberculosis, ParamyxovirusM.paratuberculosis, Paramyxovirus,, and and HelicobacterHelicobacter species have received the greatest attention, however, species have received the greatest attention, however, further studies have not confirmed a disease associationfurther studies have not confirmed a disease association

* Multiple pathogens (* Multiple pathogens (Salmonella, Shigella,Salmonella, Shigella,andand CampylobacterCampylobacter sp.) may initiate IBD by triggering an sp.) may initiate IBD by triggering an inflammatory response that the mucosal immune system inflammatory response that the mucosal immune system may fail to controlmay fail to control

* Normal flora, as * Normal flora, as Bacteroides Bacteroides sp may induce sp may induce inflammation in CDinflammation in CD

* Psychosocial factors can cause exacerbation of * Psychosocial factors can cause exacerbation of symptomssymptoms

@ Host factors@ Host factors

* In IBD, activated CD4+ T cells present in the * In IBD, activated CD4+ T cells present in the lamina propria and peripheral blood secrete lamina propria and peripheral blood secrete inflammatory cytokines which may activate other inflammatory cytokines which may activate other inflammatory cells (macrophages and B cells) or inflammatory cells (macrophages and B cells) or may recruit other lymphocytes, inflammatory may recruit other lymphocytes, inflammatory leukocytes, and mononuclear cells from the leukocytes, and mononuclear cells from the peripheral vasculature into the gutperipheral vasculature into the gut

* Once initiated in IBD, the immune inflammatory * Once initiated in IBD, the immune inflammatory response is perpetuated as a consequence of T- response is perpetuated as a consequence of T- cell activationcell activation

Many changes in the body’s immune system Many changes in the body’s immune system have been discovered in patients with IBD. have been discovered in patients with IBD. What is still unknown is what causes those What is still unknown is what causes those changes to happen. There is a large amount of changes to happen. There is a large amount of research being done in this area.research being done in this area.

There is a little evidence that stress causes There is a little evidence that stress causes IBD. As with other illnesses, stress may IBD. As with other illnesses, stress may aggravate symptoms and require a treatment aggravate symptoms and require a treatment program.program.

PATHOLOGY:PATHOLOGY: MacroscopicMacroscopic features,features,

UCUC is a mucosal disease that involves the rectum and is a mucosal disease that involves the rectum and may extend to involve all or part of the colonmay extend to involve all or part of the colon* 40 to 50%,is limited to the rectum and rectosigmoid* 40 to 50%,is limited to the rectum and rectosigmoid* 30 to 40%, extends beyond the sigmoid but not the * 30 to 40%, extends beyond the sigmoid but not the whole colonwhole colon* 20% have total colitis (10-20% of those, have * 20% have total colitis (10-20% of those, have “backwash ileitis”)“backwash ileitis”)* Spread occurs in continuity (no skip areas)* Spread occurs in continuity (no skip areas)

MildMild,erythema, loss of vascular pattern, contact bleeding,erythema, loss of vascular pattern, contact bleeding

ModerateModerate,granular, hemorrhagic, edematous, spont bled,granular, hemorrhagic, edematous, spont bled

SevereSevere, purulent exudate, ulcers, intense inflammation. , purulent exudate, ulcers, intense inflammation.

•* In long-standing disease pseudopolyps may be * In long-standing disease pseudopolyps may be present, the mucosa appears atrophic and featureless, present, the mucosa appears atrophic and featureless, the colon becomes narrowed and shortthe colon becomes narrowed and short

* In severe disease, the wall becomes very thin, severely * In severe disease, the wall becomes very thin, severely ulcerated mucosa, toxic megacolon may occur leading ulcerated mucosa, toxic megacolon may occur leading to perforationto perforation

Microscopic featuresMicroscopic features

Crypts are distorted, inflammatory cells as plasma cells, Crypts are distorted, inflammatory cells as plasma cells, lymphocytes, neutrophils, lymphoid aggregates, edema, lymphocytes, neutrophils, lymphoid aggregates, edema, hemorrhage, crypt abscesses, and Goblet cell depletionhemorrhage, crypt abscesses, and Goblet cell depletionDistinction between UC & CD is not possible in Distinction between UC & CD is not possible in 10-15%10-15%

PATHOLOGY:PATHOLOGY: Macroscopic featuresMacroscopic features

CDCD affects any part of the GIT from the mouth to anus affects any part of the GIT from the mouth to anus* 30 to 40% have small bowel disease alone* 30 to 40% have small bowel disease alone* 40 to 55% have both small and large bowel disease* 40 to 55% have both small and large bowel disease* 15 to 25% have colitis alone* 15 to 25% have colitis aloneIn the 75% of patients with small bowel disease, the In the 75% of patients with small bowel disease, the terminal ileum is involved in 90%terminal ileum is involved in 90%

* Unlike * Unlike UCUC, the rectum is often spared in , the rectum is often spared in CDCD* * CDCD is segmental, with skip areas is segmental, with skip areas* Perirectal fistulas, fissures, abscesses, skin tags, and * Perirectal fistulas, fissures, abscesses, skin tags, and anal stenosis are present in about one-thirdanal stenosis are present in about one-third* May involve the liver and the pancreas* May involve the liver and the pancreas

CDCD is a transmural process, is a transmural process,MildMild, aphthous or superficial ulcerations, aphthous or superficial ulcerationsSevereSevere disease, stellate ulcerations gives the disease, stellate ulcerations gives the “cobblestone”appearance“cobblestone”appearancePseudopolyps can formPseudopolyps can formAdhesions, strictures, and fistulasAdhesions, strictures, and fistulas

Microscopic featuresMicroscopic features

Aphthoid ulcers, aggregations of macrophages, and Aphthoid ulcers, aggregations of macrophages, and noncaseating granulomas in all layers of the bowel wall, noncaseating granulomas in all layers of the bowel wall, LN, mesentery, peritoneum, liver, and pancreas.LN, mesentery, peritoneum, liver, and pancreas.

Granulomas are pathognomonic of Granulomas are pathognomonic of CDCD but present in but present in only half of the casesonly half of the cases

Clinical Presentation:Clinical Presentation:Ulcerative ColitisUlcerative Colitis

Symptoms typically occurs between 15-40 y of Symptoms typically occurs between 15-40 y of age, with a second peak in incidence between age, with a second peak in incidence between 50-80 y of age. Men and women are equally 50-80 y of age. Men and women are equally affected. Ulcerative colitis occurs only in the affected. Ulcerative colitis occurs only in the colon or rectum. When it is located only in the colon or rectum. When it is located only in the rectum, it is called proctitis. Inflammation of the rectum, it is called proctitis. Inflammation of the rectum and colon keeps water from being rectum and colon keeps water from being absorbed into the bloodstream and results in absorbed into the bloodstream and results in diarrhea. diarrhea.

* Bloody diarrhea with mucus is the hall mark* Bloody diarrhea with mucus is the hall mark* Onset, gradual or abrupt, may be previous * Onset, gradual or abrupt, may be previous episodic diarrhea, may be triggered by infectionepisodic diarrhea, may be triggered by infection* Bowel frequency, related to severity* Bowel frequency, related to severity* Crampy abdominal discomfort* Crampy abdominal discomfort* Fever, malaise, and anorexia during acute * Fever, malaise, and anorexia during acute attackattack* Tachycardia, tenderness , and distension* Tachycardia, tenderness , and distension* Leucocytosis and hypoalbuminemia* Leucocytosis and hypoalbuminemia** Young patients with severe disease may appear Young patients with severe disease may appear misleadingly wellmisleadingly well

Some people may be very tired and have weight loss, Some people may be very tired and have weight loss, abdominal pain, and loss of body fluids and nutrients. abdominal pain, and loss of body fluids and nutrients. Bleeding may be serious, leading to anemia .Bleeding may be serious, leading to anemia .

Ulcerative colitis is an illness that has periods of remission and Ulcerative colitis is an illness that has periods of remission and relapse . Half of the people who have ulcerative colitis have relapse . Half of the people who have ulcerative colitis have only mild symptoms. Others have frequent fever, bloody only mild symptoms. Others have frequent fever, bloody diarrhea, nausea, and severe abdominal cramps.diarrhea, nausea, and severe abdominal cramps.

Some people with severe symptoms of ulcerative colitis must Some people with severe symptoms of ulcerative colitis must go to the hospital to correct malnutrition and stop diarrhea and go to the hospital to correct malnutrition and stop diarrhea and loss of blood. In the hospital, a patient may need a treatment loss of blood. In the hospital, a patient may need a treatment program including a special diet and feeding through a vein. program including a special diet and feeding through a vein. Sometimes surgery is needed.Sometimes surgery is needed.

Assessing the severity of UCAssessing the severity of UC

MildMild ModerateModerate SevereSevere

Motions/dayMotions/day <4<4 4-64-6 >6>6

Rectal bleedRectal bleed SmallSmall ModerateModerate LargeLarge

TempTemp NormalNormal <37.5<37.5 >37.5>37.5

Pulse ratePulse rate NormalNormal >90>90

HemoglobinHemoglobin MildMild 10.5-1110.5-11 <10.5<10.5

ESRESR <30<30 >30>30

EndoscopyEndoscopy Erythema,fine Erythema,fine gran, loss vascgran, loss vasc

Contact bleedContact bleed

Spont bleedingSpont bleeding

Edema, more Edema, more granulargranular

Hge, severe Hge, severe inflam, ulcers, inflam, ulcers, exudateexudate

Extraintestinal manifestationsExtraintestinal manifestations

May occur in up to 25% of patients with May occur in up to 25% of patients with ulcerative colitis. These may include:ulcerative colitis. These may include:

Osteoporosis in 15%Osteoporosis in 15%

Oral ulcerations in 10%Oral ulcerations in 10%

Arthritis in 5% to 10%Arthritis in 5% to 10%

PSC & cholangioca in 3%, less common in CDPSC & cholangioca in 3%, less common in CD

Uveitis in 0.5% to 3%Uveitis in 0.5% to 3%

PG and EN in 0.5% to 2.0%PG and EN in 0.5% to 2.0%

DVT in 0.3%, and PE in 0.2%.DVT in 0.3%, and PE in 0.2%.

MANAGEMENT:MANAGEMENT:

* Establish the diagnosis* Establish the diagnosisStool examinationStool examination

Sigmoidoscopy and biopsySigmoidoscopy and biopsy

ColonoscopyColonoscopy

Air contrast barium enemaAir contrast barium enema

* * Establish the severityEstablish the severityClinical, Hgb, WBC, ESR, C-reactive protein, Clinical, Hgb, WBC, ESR, C-reactive protein,

albumin, hypokal, plain AXR, sigmoidoscopy albumin, hypokal, plain AXR, sigmoidoscopy

Establish the extent:Establish the extent:Plain AXR, colonoscopy and serial biopsy, Plain AXR, colonoscopy and serial biopsy, barium enemabarium enemaThe risk of proximal extension of distal disease is The risk of proximal extension of distal disease is about 15% at 5 years and 30% at 10 yearsabout 15% at 5 years and 30% at 10 years

Investigations of relapse:Investigations of relapse:* Sigmoidoscopy and biopsy* Sigmoidoscopy and biopsy* Other lab work like initial attack* Other lab work like initial attack* * Repeat colonoscopy is unnecessary unless the Repeat colonoscopy is unnecessary unless the extent is thought to be changedextent is thought to be changed

Outpatient FU in remission:Outpatient FU in remission:

* Sigmoid. and biopsy Is only necessary if a * Sigmoid. and biopsy Is only necessary if a relapse occursrelapse occurs* Surveillance colonoscopy and multiple biopsy * Surveillance colonoscopy and multiple biopsy may be indicated for total colitis after symptoms may be indicated for total colitis after symptoms for 8 years, and 10-12 y for left-sided disease.for 8 years, and 10-12 y for left-sided disease.* Annual CBC, and LFT* Annual CBC, and LFT* Persistently (> 3 months), or > 3 fold elevation * Persistently (> 3 months), or > 3 fold elevation in ALP, are indications for U/S to exclude gall in ALP, are indications for U/S to exclude gall stones, before ERCP to look for PSCstones, before ERCP to look for PSC

Total colitis and symptoms for 8 yearsTotal colitis and symptoms for 8 years

colonoscopy and biopsy every 10 cm colonoscopy and biopsy every 10 cm

quiescent histology abnormal histologyquiescent histology abnormal histology

repeat every 1-3 y carcinoma dysplasia repeat every 1-3 y carcinoma dysplasia

high grade low high grade low repeat at 6 mo repeat at 6 mo

persist persist colectomy colectomy

DIFFERENTIAL DIAGNOSIS:DIFFERENTIAL DIAGNOSIS:

* Infective colitis, Salmo, Shig, E.coli, Campylo, * Infective colitis, Salmo, Shig, E.coli, Campylo, Entamoeba, Clostridium, CMV, and SchistosomEntamoeba, Clostridium, CMV, and Schistosom

* Crohn’s disease* Crohn’s disease

* Ischemic colitis, radiation, pseudomembranous,* Ischemic colitis, radiation, pseudomembranous,

* Carcinoma, polyps* Carcinoma, polyps* Diverticular disease* Diverticular disease* Non-specific colitis, eosinophilic enterocolitis* Non-specific colitis, eosinophilic enterocolitis* IBS may coexist with UC* IBS may coexist with UC

UCUC CDCDBloody diarrheaBloody diarrhea 90-100%90-100% 50%50%

Abdominal massAbdominal mass Very rareVery rare CommonCommon

Perianal diseasePerianal disease Very uncommonVery uncommon 30-50%30-50%

Rectal sparingRectal sparing NeverNever 50%50%

HistologyHistology Mucosal,cryptitis,Mucosal,cryptitis,Goblet cell Goblet cell

depletion, no depletion, no granulomagranuloma

Transmural,normTransmural,normal crypts,normal al crypts,normal

Goblet,granuloma Goblet,granuloma diagnosticdiagnostic

MucosaMucosa Shallow ulcersShallow ulcers Deep Deep

DistributionDistribution ContinousContinous Skip areasSkip areas

StricturesStrictures Very rareVery rare commoncommon

FistulaeFistulae NeverNever CommonCommon

TREATMENT OF UCTREATMENT OF UC

Prompt treatment of acute attacksPrompt treatment of acute attacks

MaintenanceMaintenance

Selection of patients for colectomySelection of patients for colectomy

Detection of colorectal carcinomaDetection of colorectal carcinoma

Patient educationPatient education

UC Treatment PyramidUC Treatment Pyramid

Disease activityDisease activity

SevereSevere

ModerateModerate

MildMild

SugeryCiclosporin

Systemic steroids

Topical and/or oral steroidsaminosalicylates

Azathioprine6-MPIFX

Mild attacksMild attacks

The European approach is to use systemic The European approach is to use systemic steroids at an early stage, although in the USA steroids at an early stage, although in the USA the tendency is to use high-dose oral and the tendency is to use high-dose oral and topical mesalazinetopical mesalazine

Response on mesalazine 4 g/day is 70%, but Response on mesalazine 4 g/day is 70%, but remission is only achieved in 30% after 6 remission is only achieved in 30% after 6 weeks, compared to 80% after 2 weeks on weeks, compared to 80% after 2 weeks on steroidssteroids

Recommended treatment:Recommended treatment:

2-week trial of topical mesalazine (supp, foam 2-week trial of topical mesalazine (supp, foam or liquid enema) and oral mesalazine ≥ 4 g or liquid enema) and oral mesalazine ≥ 4 g daily as a single or 2 divided doses.daily as a single or 2 divided doses.

If no improvement within 2 weeks, start oral If no improvement within 2 weeks, start oral prednisolone 20 mg daily for 1 month, then prednisolone 20 mg daily for 1 month, then reduce by 5 mg /week.reduce by 5 mg /week.

Failure to improve after 2 weeks, treat as a Failure to improve after 2 weeks, treat as a moderate attack.moderate attack.

Deterioration is an indication for admission.Deterioration is an indication for admission.

Moderate attacksModerate attacks

Prednisolone 40 mg daily for 1 week, then 30 Prednisolone 40 mg daily for 1 week, then 30 mg daily for 1 week, then 20 mg daily for 1 mg daily for 1 week, then 20 mg daily for 1 month, then reduce by 5 mg / weekmonth, then reduce by 5 mg / week

Mesalazine enema at night or steroid enema if Mesalazine enema at night or steroid enema if mesalazine not toleratedmesalazine not tolerated

Continue oral mesalazine at previous doseContinue oral mesalazine at previous dose

( ≥ 4 g daily) as a single or 2 divided doses( ≥ 4 g daily) as a single or 2 divided doses

Admission is not essential unless fail to Admission is not essential unless fail to improve within 2 weeks improve within 2 weeks

Severe attackSevere attack* Immediate admission, surgeon informed, daily * Immediate admission, surgeon informed, daily AXR, CBC, C-reactive protein, U&E, stool ex, and AXR, CBC, C-reactive protein, U&E, stool ex, and albuminalbumin* NPO except sips of fluid only, IV fluids, blood if * NPO except sips of fluid only, IV fluids, blood if Hgb < 10, parenteral nutrition is only needed for Hgb < 10, parenteral nutrition is only needed for malnourishedmalnourished* IV hydrocortisone 100 mg/6-8 h or * IV hydrocortisone 100 mg/6-8 h or methylprednisolone 20 mg tds for 5 daysmethylprednisolone 20 mg tds for 5 days* Rectal steroids (Hydrocortisone 100 mg in 100 * Rectal steroids (Hydrocortisone 100 mg in 100 mL 0.9% saline dripped into rectum through a mL 0.9% saline dripped into rectum through a soft cathetersoft catheter* Stop oral aminosalicylates * Stop oral aminosalicylates

• Antibiotics (metronidazole /or ciproflox)Antibiotics (metronidazole /or ciproflox)• Daily or twice daily re-examination, Pulse, Daily or twice daily re-examination, Pulse,

Temp, Abdominal girth, tenderness, and stool Temp, Abdominal girth, tenderness, and stool frequency & appearancefrequency & appearance

• After 3 days assess simple prognostic factors, After 3 days assess simple prognostic factors, stool frequency and CRP, if > 45mg/L consider stool frequency and CRP, if > 45mg/L consider ciclosporin, infliximab, discuss plans for ciclosporin, infliximab, discuss plans for surgery, and continue IV hydrocortisonesurgery, and continue IV hydrocortisone

• Failure to respond after 5-7 days or Failure to respond after 5-7 days or deterioration at any stage is an indication for deterioration at any stage is an indication for colectomy. Delay increases mortalitycolectomy. Delay increases mortality

• 40 % are in remission after 5 days, and 30% 40 % are in remission after 5 days, and 30% deteriorate and have colectomy. Another group deteriorate and have colectomy. Another group (30%) improve, but relapse on introducing food (30%) improve, but relapse on introducing food or start oral steroids, usually means that or start oral steroids, usually means that colectomy is requiredcolectomy is required

• Those who improve,40%, will start oral Those who improve,40%, will start oral prednisoloneprednisolone 40mg/day 1 week , then reduce 40mg/day 1 week , then reduce prednisoloneprednisolone 30mg/day 1 w, then 20mg/day 1 30mg/day 1 w, then 20mg/day 1 month, then reduce by 5 mg/weekmonth, then reduce by 5 mg/week

• Azathioprine or mercaptopurine can be started Azathioprine or mercaptopurine can be started in the last month of treatment as steroids are in the last month of treatment as steroids are withdrawnwithdrawn

Treatment of active UC after topical treatment Treatment of active UC after topical treatment (steroid or 5-ASA enema) for up to 2 weeks(steroid or 5-ASA enema) for up to 2 weeks

DrugDrug MildMild

2 weeks2 weeksModerateModerate

2 weeks2 weeksSevereSevere

PrednisolonePrednisolone 20mg/d 1mo20mg/d 1mo

15mg/d 1 w15mg/d 1 w

10mg/d 1 w10mg/d 1 w

5mg/d 1 w5mg/d 1 w

40mg/d 1 w40mg/d 1 w

30mg/d 1 w30mg/d 1 w

Then as for Then as for mild attackmild attack

Admit for iv Admit for iv steroidssteroids

EnemasEnemas Continue Continue whilst bleedwhilst bleed

ContinueContinue

Twice dailyTwice daily

Oral 5-ASAOral 5-ASA continuecontinue continuecontinue nonnon

ProctitisProctitis* * Topical mesalazineTopical mesalazine (mesalazine supp 1 g at night) (mesalazine supp 1 g at night) and and oraloral salicylatessalicylates are often sufficient, but it can be very are often sufficient, but it can be very refractory, even to oral steroids.refractory, even to oral steroids.

* * MesalazineMesalazine enemasenemas, more effective than steroid , more effective than steroid enemas, but less well tolerated. The combination enemas, but less well tolerated. The combination (steroid enema AM, mesalazine at night) may be better (steroid enema AM, mesalazine at night) may be better than either alone and is useful for refractory disease.than either alone and is useful for refractory disease.

* Patients usually find foam enemas or supp easier to * Patients usually find foam enemas or supp easier to retain than liquid enemasretain than liquid enemas

* Failure to control symptoms within 2-4 weeks, is an * Failure to control symptoms within 2-4 weeks, is an indication for indication for prednisoloneprednisolone 20mg/day for 1 month, then 20mg/day for 1 month, then reduce by 5 mg/weekreduce by 5 mg/week

Refractory proctitis or distal colitis:Refractory proctitis or distal colitis:

This occurs in about 25%, some also relapse rapidly This occurs in about 25%, some also relapse rapidly after a course of steroids, or become dependent on after a course of steroids, or become dependent on steroids:steroids:

•Consider poor compliance and reasons, and whether IBS is Consider poor compliance and reasons, and whether IBS is contributingcontributing

•Confirm disease activity by sigmoidoscopy and biopsyConfirm disease activity by sigmoidoscopy and biopsy

•Abdominal X-ray, treat proximal constipation Abdominal X-ray, treat proximal constipation

•StartStart mesalazinemesalazine 1 g 1 g suppsupp at night, in addition to at night, in addition to steroidsteroid enemasenemas in the morningin the morning

•Restart Restart prednisoloneprednisolone 40mg/day, as for moderate attack, together 40mg/day, as for moderate attack, together with with azathioprineazathioprine 2 to 2.5mg/kg/day, or 2 to 2.5mg/kg/day, or mercaptopurinemercaptopurine

•Dietary reduction of milk or resistant starches may helpDietary reduction of milk or resistant starches may help

•Admission for intensive treatment, before considering colectomy, Admission for intensive treatment, before considering colectomy, but best refer to a specialist centrebut best refer to a specialist centre

Mesalamine is effective treatment for Mesalamine is effective treatment for patients with isolated proctitis, trials patients with isolated proctitis, trials

suggestsuggest..Medical News TodayMedical News Today (12/7) reports that Asacol (mesalamine) (12/7) reports that Asacol (mesalamine) "is an effective and well-tolerated treatment for patients with all "is an effective and well-tolerated treatment for patients with all extents of ulcerative colitis (UC), including isolated proctitis," extents of ulcerative colitis (UC), including isolated proctitis," according to data from two clinical trials. Researchers according to data from two clinical trials. Researchers combined and analyzed data from the Assessing the Safety combined and analyzed data from the Assessing the Safety and Clinical Efficacy of a New Dose of 5-ASA (ASCEND) trials and Clinical Efficacy of a New Dose of 5-ASA (ASCEND) trials "to evaluate the efficacy of oral delayed-release Asacol dosed "to evaluate the efficacy of oral delayed-release Asacol dosed at 2.4 g/day to treat active UC flares in patients with isolated at 2.4 g/day to treat active UC flares in patients with isolated proctitis." They found that participants that took 2.4g of Asacol proctitis." They found that participants that took 2.4g of Asacol per day for six weeks "experienced significant improvement as per day for six weeks "experienced significant improvement as early as three weeks, and sustained improvement at six weeks, early as three weeks, and sustained improvement at six weeks, of UC symptoms. At six weeks 83 % of patients had of UC symptoms. At six weeks 83 % of patients had improvement in rectal bleeding, 75 % had mucosal healing and improvement in rectal bleeding, 75 % had mucosal healing and 57 % had reduced stool frequency." 57 % had reduced stool frequency."

Steroid-refractory patientsSteroid-refractory patients

Controlled studies have been shown that i.v. Controlled studies have been shown that i.v. ciclosporinciclosporin infusion 2 mg/kg/d for 14 d induces infusion 2 mg/kg/d for 14 d induces remission in 80%, if this followed by oral remission in 80%, if this followed by oral ciclosporinciclosporin 8mg/kg/d plus 8mg/kg/d plus azathioprine,azathioprine, after 3 months stop after 3 months stop ciclosporinciclosporin.. At 6 months 45% maintained remission, check level on At 6 months 45% maintained remission, check level on alternate days ( target 150-250ng/ml).alternate days ( target 150-250ng/ml).

Over 1 month taper Over 1 month taper prednisoloneprednisolone from 40 mg/d to from 40 mg/d to 20mg/d and continue for 2-3 months, start to taper from 20mg/d and continue for 2-3 months, start to taper from 20 to 0 mg over 4-8 weeks ( 1 week after stopping 20 to 0 mg over 4-8 weeks ( 1 week after stopping ciclosporinciclosporin), If relapse at any point during tapering ), If relapse at any point during tapering refer for colectomyrefer for colectomy GUT . 2003;52;2GUT . 2003;52;2

Triple immunosuppressive therapy gives Triple immunosuppressive therapy gives promising results, reducing relapses and need promising results, reducing relapses and need for colectomy,for colectomy,

CiclosporinCiclosporin iv infusion 2 mg/kg/day, till iv infusion 2 mg/kg/day, till

response is induced (2-5 days), then this is response is induced (2-5 days), then this is substituted by:substituted by:Oral Oral ciclosporinciclosporin 5-8 mg/kg/day plus 5-8 mg/kg/day plusAzathioprineAzathioprine 2-2.5mg/kg/day plus2-2.5mg/kg/day plusPrednisolonePrednisolone in reducing doses in reducing dosesCiclosporinCiclosporin is progressively reduced until is progressively reduced until discontinuation within 3 months,discontinuation within 3 months,

Gastro.Hepatol,2004 Jan;27(1):1-5Gastro.Hepatol,2004 Jan;27(1):1-5

Role of anti-TNF in treating IBDRole of anti-TNF in treating IBD

There are 3 available anti-TNF,There are 3 available anti-TNF,

* Infliximab,IFX, (Remicade), i/v* Infliximab,IFX, (Remicade), i/v

* Adalimumab (Humira), s/c* Adalimumab (Humira), s/c

* Certolizumab, s/c* Certolizumab, s/c

In UC we only have data in Infliximab but our In UC we only have data in Infliximab but our anticipation is that all 3 drugs have similar anticipation is that all 3 drugs have similar resultsresults

In 2001In 2001

Infliximab was tried in 11 patients with severe Infliximab was tried in 11 patients with severe UC refractory to steroidsUC refractory to steroids

Used in 3 doses, Used in 3 doses,

5 mg/kg iv on day zero, 5 mg/kg iv on day zero, 10 mg/kg iv on week 2, and 10 mg/kg iv on week 2, and

20 mg/kg iv on week 820 mg/kg iv on week 8

50% responded, avoided colectomy50% responded, avoided colectomy

In 2003In 2003

Infliximab was tried in 43 patientsInfliximab was tried in 43 patients

39% responded39% responded

In 2004In 2004

IFX was compared to steroids in 2 trialsIFX was compared to steroids in 2 trials

13 patients trial13 patients trial

Induced response in 83% Vs 85% in steroid groupInduced response in 83% Vs 85% in steroid group

20 patients trial, both drugs induced response in 100% 20 patients trial, both drugs induced response in 100% of patientsof patients

In 2005In 2005

IFX was compared to placebo in 45 patientsIFX was compared to placebo in 45 patients

It produced response in 71% compared to It produced response in 71% compared to 33% for placebo group33% for placebo group

Multicenter, double blinded, randomized, Multicenter, double blinded, randomized, placebo controlled trials of infliximab have placebo controlled trials of infliximab have demonstrated excellent clinical response and demonstrated excellent clinical response and remission rates in steroid and remission rates in steroid and immunomodulator refractory/dependent immunomodulator refractory/dependent Crohn’s disease as well as steroid and Crohn’s disease as well as steroid and immunomodulator refractory/dependent immunomodulator refractory/dependent ulcerative colitis.ulcerative colitis.

Gastroenterology 2006; 130: 935-939. Infect Med 2006; 23: 99-114. Gastroenterology 2006; 130: 935-939. Infect Med 2006; 23: 99-114.

However, the potential benefits of therapy need to be However, the potential benefits of therapy need to be weighed against potential risks to the patient. There weighed against potential risks to the patient. There have been many reports of major infections seen with have been many reports of major infections seen with infliximab, including primary and disseminated infliximab, including primary and disseminated tuberculosis, pneumonia, sepsis, urinary tract tuberculosis, pneumonia, sepsis, urinary tract infections, abscesses and peritonitis. Systemic infections, abscesses and peritonitis. Systemic infections, including cytomegalovirus, infections, including cytomegalovirus, coccidioidomycosis, aspergillosis, disseminated coccidioidomycosis, aspergillosis, disseminated histoplasmosis, candidiasis, listeriosis, cutaneous histoplasmosis, candidiasis, listeriosis, cutaneous Nocardia and Pneumocystis carinii pneumonia, have Nocardia and Pneumocystis carinii pneumonia, have also been described in patients treated with infliximab. also been described in patients treated with infliximab. In addition, there have been reports of new onset In addition, there have been reports of new onset heart failure, worsening of existing heart failure, heart failure, worsening of existing heart failure, demyelination disorders and drug induced lupus. demyelination disorders and drug induced lupus.

Infect Med 2006; 23: 99-114. Infect Med 2006; 23: 99-114.

Colombel and colleagues summarized the side effects Colombel and colleagues summarized the side effects in the first 500 patients treated with infliximab at the in the first 500 patients treated with infliximab at the Mayo Clinic. They reported serious or severe Mayo Clinic. They reported serious or severe infections in 8.2 % of the patients possibly related to infections in 8.2 % of the patients possibly related to infliximab. Overall, five deaths (1 %) were felt to be infliximab. Overall, five deaths (1 %) were felt to be related to infliximab. related to infliximab. Another study included 217 patients with IBD in Another study included 217 patients with IBD in Sweden and observed serious or severe infections in Sweden and observed serious or severe infections in 8.3 % of patients. They found a mortality rate of 2.8 %, 8.3 % of patients. They found a mortality rate of 2.8 %, with fatal non-Hodgkin’s lymphomas in two patients, with fatal non-Hodgkin’s lymphomas in two patients, fatal sepsis in two patients, fatal Pneumocystis carinii fatal sepsis in two patients, fatal Pneumocystis carinii in one patient and a fatal pulmonary embolus in one in one patient and a fatal pulmonary embolus in one patient. patient. Additional side effects of infliximab observed in these Additional side effects of infliximab observed in these two clinical trials included serum sickness-like reaction two clinical trials included serum sickness-like reaction (2.5 %), drug induced lupus (0.5 %) and one (2.5 %), drug induced lupus (0.5 %) and one demyelination disorder.demyelination disorder.

Prevention of the development of antibodies to infliximab (ATI) Prevention of the development of antibodies to infliximab (ATI) has proven to be a particularly important reason to begin has proven to be a particularly important reason to begin immunomodulators before infliximab. In clinical trials, patients immunomodulators before infliximab. In clinical trials, patients on stable doses of immunomodulators for at least three on stable doses of immunomodulators for at least three months prior to receiving IFX also had a lower rate of ATI months prior to receiving IFX also had a lower rate of ATI development. Furthermore, Lemann and colleagues have development. Furthermore, Lemann and colleagues have demonstrated the superior effectiveness of the combination of demonstrated the superior effectiveness of the combination of infliximab and azathioprine used together. infliximab and azathioprine used together. Therefore, biologics, such as infliximab, should be used only Therefore, biologics, such as infliximab, should be used only after optimization of immunomodulators. If a patient continues after optimization of immunomodulators. If a patient continues to have active disease, despite an adequate trial with an to have active disease, despite an adequate trial with an optimized immunomodulator, the immunomodulator is optimized immunomodulator, the immunomodulator is continued and infliximab is initiated. Subsequently, steroids are continued and infliximab is initiated. Subsequently, steroids are tapered and discontinued as rapidly as possible. This is our tapered and discontinued as rapidly as possible. This is our current standard of care according to published guidelines. current standard of care according to published guidelines. Prospective, multicenter trials to further confirm and refine this Prospective, multicenter trials to further confirm and refine this approach are in progress.approach are in progress.

Gastroenterology 2006; 130: 1054-1061. Gastroenterology 2006; 130: 1054-1061.

Therefore, only those patients who have failed both Therefore, only those patients who have failed both steroids as well as immunomodulators should receive steroids as well as immunomodulators should receive infliximab. These patients have demonstrated that infliximab. These patients have demonstrated that they have aggressive IBD, refractory to conventional they have aggressive IBD, refractory to conventional therapy, and therefore appropriately need infliximab.therapy, and therefore appropriately need infliximab.

Many patients with Crohn’s disease or ulcerative Many patients with Crohn’s disease or ulcerative colitis never require treatment with steroids. In colitis never require treatment with steroids. In addition, a significant number of patients treated with addition, a significant number of patients treated with infliximab do not respond (primary failure) or lose their infliximab do not respond (primary failure) or lose their response (secondary failure). It is important that response (secondary failure). It is important that clinicians do not recommend therapies to patients who clinicians do not recommend therapies to patients who may not benefit from them. We should avoid may not benefit from them. We should avoid needlessly exposing patients, who may have a robust needlessly exposing patients, who may have a robust and sustained response to immunomodulators, to the and sustained response to immunomodulators, to the potential side effects of biologics such as inflixpotential side effects of biologics such as inflix

Gastroenterology 2006; 130: 940-987.Gastroenterology 2006; 130: 940-987.

Furthermore, in pediatric patients with Crohn’s disease Furthermore, in pediatric patients with Crohn’s disease or ulcerative colitis, we should be particularly careful of or ulcerative colitis, we should be particularly careful of exposure to medications with potential as well as exposure to medications with potential as well as unknown long-term side effects. At this time there is unknown long-term side effects. At this time there is insufficient evidence that biologics such as infliximab insufficient evidence that biologics such as infliximab significantly change the natural history of ulcerative significantly change the natural history of ulcerative colitis or Crohn’s disease and can be used as a colitis or Crohn’s disease and can be used as a disease-modifying agent. disease-modifying agent.

Therefore, immunomodulators, not biologics such as Therefore, immunomodulators, not biologics such as infliximab, should be used first for the steroid infliximab, should be used first for the steroid refractory and/or steroid dependent outpatient with refractory and/or steroid dependent outpatient with chronic severe (moderate to severe) Crohn’s disease chronic severe (moderate to severe) Crohn’s disease or ulcerative colitis. or ulcerative colitis.

Gastroenterology 2006; 130: 940-987. Gastroenterology 2006; 130: 940-987.

Infliximab Effectively Avoids Infliximab Effectively Avoids Colectomy in Ulcerative ColitisColectomy in Ulcerative Colitis

According to a recent study, infliximab is an effective According to a recent study, infliximab is an effective and relatively safe therapy to avoid colectomy and and relatively safe therapy to avoid colectomy and maintain long-term remission for patients with severe maintain long-term remission for patients with severe refractory ulcerative colitis, while two or more infusions refractory ulcerative colitis, while two or more infusions seem to be more effective than a single infusion in the seem to be more effective than a single infusion in the short term.short term.

Alimentary Pharmacology & Therapeutics; 2007: 26(5): 747-56Alimentary Pharmacology & Therapeutics; 2007: 26(5): 747-56

Infliximab is known as a rescue therapy. Italian Infliximab is known as a rescue therapy. Italian researchers evaluated short- and long-term researchers evaluated short- and long-term effectiveness and safety of infliximab in severe effectiveness and safety of infliximab in severe refractory ulcerative colitis, assessing 83 proposed refractory ulcerative colitis, assessing 83 proposed patients with severe ulcerative colitis treated with patients with severe ulcerative colitis treated with infliximab in 10 Italian centers. infliximab in 10 Italian centers.

Patients underwent one or more infusions according to Patients underwent one or more infusions according to the choice of treating physicians. The team's short-the choice of treating physicians. The team's short-term outcome was colectomy or death two months term outcome was colectomy or death two months after the first infusion. The long-term outcome was after the first infusion. The long-term outcome was survival free from colectomy, and the researchers survival free from colectomy, and the researchers recorded safety data. recorded safety data.

Alimentary Pharmacology & TherapeuticsAlimentary Pharmacology & Therapeutics; 2007: 26(5): 747-56; 2007: 26(5): 747-56

The researchers noted that 12 patients underwent The researchers noted that 12 patients underwent colectomy within two months. Of these, one patient colectomy within two months. Of these, one patient died of died of Legionella pneumophilaLegionella pneumophila infection 12 days after infection 12 days after infliximab. infliximab.

Early colectomy rates were higher in patients receiving Early colectomy rates were higher in patients receiving one infusion, compared with those receiving two or one infusion, compared with those receiving two or more infusions. The team followed-up 70 patients who more infusions. The team followed-up 70 patients who survived colectomy and did not experience any fatal survived colectomy and did not experience any fatal complications for a median time of 23 months. The complications for a median time of 23 months. The researchers observed that 58 patients avoided researchers observed that 58 patients avoided colectomy during the follow-up. The team maintained colectomy during the follow-up. The team maintained 42 patients on immunosuppressive drugs. 42 patients on immunosuppressive drugs.

Alimentary Pharmacology & TherapeuticsAlimentary Pharmacology & Therapeutics; 2007: 26(5): 747-56; 2007: 26(5): 747-56

Adalimumab Induces Remissions in CD Adalimumab Induces Remissions in CD

Adalimumab, a fully human tumor necrosis factor Adalimumab, a fully human tumor necrosis factor antagonist, is an effective treatment for Crohn's antagonist, is an effective treatment for Crohn's disease in patients who are naĩve to the chimeric disease in patients who are naĩve to the chimeric tumor necrosis factor antagonist, infliximab. No anti-tumor necrosis factor antagonist, infliximab. No anti-tumor necrosis factor agent has been evaluated tumor necrosis factor agent has been evaluated prospectively in patients with Crohn's disease who had prospectively in patients with Crohn's disease who had responded to another anti-tumor necrosis factor agent responded to another anti-tumor necrosis factor agent and then lost that response or were intolerant of the and then lost that response or were intolerant of the agent. Doctors determined whether adalimumab agent. Doctors determined whether adalimumab induces remissions more frequently than placebo in induces remissions more frequently than placebo in Crohn's disease.Crohn's disease.

Patients included in the study had symptoms Patients included in the study had symptoms despite despite infliximab therapy or could not take infliximabinfliximab therapy or could not take infliximab because because of adverse events. The team conducted a of adverse events. The team conducted a fourfour-week, -week, randomized, double-blind, placebo-controlled trial randomized, double-blind, placebo-controlled trial between 2004 and 2005, assessing between 2004 and 2005, assessing 325325 adults 18 to adults 18 to 75 years of age who had a history of Crohn's disease 75 years of age who had a history of Crohn's disease for four months or more that was moderate to severe for four months or more that was moderate to severe at baseline. Patients were randomly assigned to at baseline. Patients were randomly assigned to receive induction doses of adalimumab, receive induction doses of adalimumab, 160 mg160 mg and and 80 mg80 mg, at weeks , at weeks zerozero and and twotwo, respectively, or , respectively, or placebo at the same time points. The primary end placebo at the same time points. The primary end point was induction of remission at week four. point was induction of remission at week four. Decreases in Crohn's Disease Activity Index score by Decreases in Crohn's Disease Activity Index score by 70 or more and 100 or more points were also 70 or more and 100 or more points were also measured.measured.

A total of A total of 301301 patients completed the trial. The patients completed the trial. The team noted that 21 % of patients in the team noted that 21 % of patients in the adalimumab group versus 7 % of those in the adalimumab group versus 7 % of those in the placebo group achieved remission at week placebo group achieved remission at week four. The team found a 70-point response four. The team found a 70-point response occurred at week four in 52 % of patients in the occurred at week four in 52 % of patients in the adalimumab group versus 34 % of patients in adalimumab group versus 34 % of patients in the placebo group. The team noted that two of the placebo group. The team noted that two of 159 patients in the adalimumab group, and four 159 patients in the adalimumab group, and four of 166 patients in the placebo group of 166 patients in the placebo group discontinued treatment because of adverse discontinued treatment because of adverse events. The team found that no patients in the events. The team found that no patients in the adalimumab group, and four of 166 patients in adalimumab group, and four of 166 patients in the placebo group had a serious infection.the placebo group had a serious infection.

Annals of Internal Medicine; 2007: 146 (12): 829-38Annals of Internal Medicine; 2007: 146 (12): 829-38

Indications for emergency surgery:Indications for emergency surgery:

* toxic dilatation* toxic dilatation

* Perforation* Perforation

* Massive bleeding, if not stopped after 4 units blood * Massive bleeding, if not stopped after 4 units blood

* Failure of a severe attack to respond to i.v. * Failure of a severe attack to respond to i.v. steroidssteroids and/or i.v.and/or i.v. ciclosporin, ciclosporin, or ivor iv infliximab infliximab within 5 days, as within 5 days, as the operative morbidity and mortality increases if surgery the operative morbidity and mortality increases if surgery is inappropriately delayedis inappropriately delayed

* Patients with incomplete response who deteriorate * Patients with incomplete response who deteriorate when food is introducedwhen food is introduced

MaintenanceMaintenance treatment should be continued treatment should be continued for lifefor life

* * SulphsalazineSulphsalazine 1-4g/day is cheap, well established, but 1-4g/day is cheap, well established, but poorly tolerated, and reversible oligospermia is frequentpoorly tolerated, and reversible oligospermia is frequent** MesalazineMesalazine, or , or olsalazineolsalazine* * OlsalazineOlsalazine is more effective > is more effective > mesalazinemesalazine in distal in distal colitiscolitis* * OlsalazineOlsalazine, , sulphasalazinesulphasalazine, and slow-release , and slow-release mesalazine (mesalazine (pentasapentasa) are less nephrotoxic than pH-) are less nephrotoxic than pH-dependent release compounds (dependent release compounds (asacolasacol))* * AzathioprineAzathioprine, , 6-MP6-MP, and , and IFXIFX

** SteroidsSteroids have no effect on relapse rate and should be have no effect on relapse rate and should be stopped once remission occurs.stopped once remission occurs.

Indications of elective surgery:Indications of elective surgery:

Colectomy is the only cure for ulcerative colitis, Colectomy is the only cure for ulcerative colitis, colectomy and ileoanal pouch is the operation of colectomy and ileoanal pouch is the operation of choicechoice

* Continuous symptoms, with general ill health and * Continuous symptoms, with general ill health and anemia despite treatmentanemia despite treatment

* Frequent relapses unresponsive to medical * Frequent relapses unresponsive to medical treatmenttreatment

* High-grade dysplasia, or malignancy* High-grade dysplasia, or malignancy

Complications:Complications:

* Toxic dilatation* Toxic dilatation

* Perforation* Perforation

* Massive hemorrhage * Massive hemorrhage

* Carcinoma* Carcinoma

UC in pregnancy:UC in pregnancy:

Maintenance therapy should almost always be continuedMaintenance therapy should almost always be continuedRelapse is treated in the standard wayRelapse is treated in the standard way

CONCLUSIONCONCLUSION

It is important to recognize that not all It is important to recognize that not all manifestations of Crohn’s disease can be manifestations of Crohn’s disease can be effectively treated with biologics, such as effectively treated with biologics, such as infliximab. infliximab. Surgical resection of severely diseased bowel Surgical resection of severely diseased bowel remains an important option for the patient with remains an important option for the patient with acute or chronic severe Crohn’s disease or acute or chronic severe Crohn’s disease or ulcerative colitis. ulcerative colitis. Surgery not only removes the diseased Surgery not only removes the diseased intestine and its associated risks, but also intestine and its associated risks, but also allows the discontinuation and avoidance of allows the discontinuation and avoidance of high dose steroids, immunomodulators and high dose steroids, immunomodulators and biologics, thereby decreasing the risk of severe biologics, thereby decreasing the risk of severe opportunistic infections and other side effects opportunistic infections and other side effects due to these medications.due to these medications.

AGA guideline in IBDAGA guideline in IBD

Corticosteroids, oral, topical, or parenteral forms used Corticosteroids, oral, topical, or parenteral forms used for acute treatment of patients with moderate to for acute treatment of patients with moderate to severe relapses of IBD. Budesonide is a poorly severe relapses of IBD. Budesonide is a poorly absorbed corticosteroid with limited bioavailability due absorbed corticosteroid with limited bioavailability due to extensive first-pass metabolism (degraded by the to extensive first-pass metabolism (degraded by the liver and red blood cells) that can produce therapeutic liver and red blood cells) that can produce therapeutic benefit with reduced systemic toxicity in patients with benefit with reduced systemic toxicity in patients with ileocecal Crohn's disease (CD). Topical agents in the ileocecal Crohn's disease (CD). Topical agents in the form of suppositories or foam have been used to treat form of suppositories or foam have been used to treat patients with proctitis, whereas enemas are effective patients with proctitis, whereas enemas are effective for application in patients with disease up to the for application in patients with disease up to the splenic flexure.splenic flexure.

Infliximab is available for treatment of patients with moderately to severely active Crohn's disease and patients with fistulizing Crohn's disease, who have had an inadequate response to conventional therapy.

Treatment of patients with infliximab markedly decreases endoscopic and histologic disease activity in Crohn's colitis .

When given as a single infusion intravenously at 5 mg/kg body weight, infliximab has a half life of approximately 10 days. Infliximab does not accumulate when given in three doses at zero, two, and eight weeks, or when given in repeated doses at eight-week intervals.

Infliximab is more expensive than other Infliximab is more expensive than other medications used to treat Crohn's disease.medications used to treat Crohn's disease.

The medication is used for Crohn's disease that The medication is used for Crohn's disease that does not improve (refractory disease) when does not improve (refractory disease) when treated with corticosteroids, aminosalicylates, treated with corticosteroids, aminosalicylates, antibiotics, azathioprine, or 6-mercaptopurine. , azathioprine, or 6-mercaptopurine. The effectiveness of infliximab and when it The effectiveness of infliximab and when it should be used is not clear, so health should be used is not clear, so health professionals may differ in how they use this professionals may differ in how they use this treatment.treatment.

Infliximab should not be used during Infliximab should not be used during pregnancy.pregnancy.