ULCERATIVE COLITIS ( MILD TO MODERATE) MANAGEMENT

TREATMENT OF MILD TO MODERATE ULCERATIVE COLITIS

DR BHAVIN MANDOWARA

TREATMENT OF MILD TO MODERATE ULCERATIVE COLITIS

OUTLINE OF PRESENTATION

PRETREATMENT EVALUATION

TREATMENT OF MILDLY OR MODERATELY ACTIVE DISEASE

MANAGEMENT OF PERSISTENT SYMPTOMS

SYMPTOMATIC TREATMENT

OTHER MANAGEMENT ISSUES

SUMMARY

PRETREATMENT EVALUATION

Definition of disease extent :

Ulcerative proctitis

Ulcerative proctosigmoiditis

Left-sided or distal ulcerative colitis

Extensive colitis

Pancolitis

Mild

Four or fewer stools per day

With or without blood

No signs of systemic toxicity, and a normal erythrocyte sedimentation rate (ESR).

Mild crampy pain, tenesmus, and periods of constipation are also common, but severe abdominal pain, profuse bleeding, fever, and weight loss are not part of the spectrum of mild disease.

Assessment of clinical severity

Moderate

Frequent loose, bloody stools (>4 per day)

Mild anemia not requiring blood transfusions

Abdominal pain that is not severe.

Minimal signs of systemic toxicity, including a low-grade fever

Adequate nutrition is usually maintained and weight loss is not associated with moderate clinical disease.



SEVERE :

Frequent loose bloody stools (6 per day)

Severe cramps

Evidence of systemic toxicity as demonstrated by a fever (temperature 37.5C), tachycardia (HR 90beats/minute),anemia (hemoglobin 8cm ) or proctosigmoiditis 5ASA suppository BD +5ASA enema BD

Foam instead of enema in case of rectal irritability

Complete healing occurs in 4-6 weeks

TREATMENT OF ULCERATIVE PROCTITIS OR PROCTOSIGMOIDITIS

SUBSEQUENT AND ALTERNATIVE APPROACHES

Cannot tolerate topical 5-ASA steroid foam preparations and steroid suppositories

Unwilling or unable to tolerate any topical medication oral 5-ASA medications

No respone to topical 5-ASA medications combination topical 5-ASA and steroid foam preparation

No response to topical medications combination therapy with oral and topical 5-ASA agents and topical steroids


Oral 5-ASA medications should be started at the lower dose and increased to the maximum tolerated dose in patients who remain symptomatic

Patients with moderate symptoms, those with previous steroid use, those with frequent relapses, and those previously treated with oral mesalamine, rectal therapy, or multiple medications are more likely to benefit from a higher dose


Oral mesalazine generally acts in two to four weeks. Patients who fail to respond to combination therapy with oral 5-ASA and topical 5-ASA/steroids require treatment with oral glucocorticoids, as discussed under left-sided colitis below


Maintainance :

not recommended in patients with a first episode of mild ulcerative proctitis that has promptly responded to treatment


MAINTAINANCE TREATMENT recommended in:

Relapse more than once a year

Proctosigmoiditis

Discontinuation for the above patients if remission is more than 2 years


Maintainance regimen:

Proctitis: once daily 5-ASA suppository

Proctosigmoiditis : once daily 5-ASA enema


INDUCTION OF REMISSION

Topical (rectal) mesalamine*

Suppository

1 gram (one suppository) twice daily

Retention enema

4 grams (one 60 mL unit) twice daily

Topical (rectal) glucocorticoids

Hydrocortisone suppository

30 mg (one suppository) twice daily

Hydrocortisone aerosol foam 10 percent

90 mg (one applicatorful) twice daily

Hydrocortisone enema

100 mg (one 60 mL unit) twice daily

SULFASALAZINE

4 to 6 grams per day in four divided doses

MESALAMINE

Delayed release enteric coated tablet

2.4 to 4.8 grams daily in three divided doses

Capsule containing delayed release enteric coated tablet

2.4 to 4.8 grams daily in three divided doses

Delayed and extended release tablet, multimatrix (MMX)

2.4 to 4.8 grams daily once daily

Capsule containing delayed release enteric coated granules

1.5 to 4.5 grams once each morning

Controlled release capsule

2 to 4 grams daily in four divided doses

Mesalamine pellets

1.5 to 4 grams daily in one to three divided doses

2 to 4 grams daily in two to four divided doses

Glucocorticoids

Budesonide delayed and extended release tablet, multimatrix (MMX)

9 mg once each morning for eight weeks

Prednisone or oral prednisolone

40 to 60 mg once each morning or in two divided doses

Intravenous prednisolone

30 mg IV every 12 hours

Methylprednisolone

16 to 20 mg IV every eight hours

Hydrocortisone

100 mg IV every eight hours

INITIAL APPROACH

Combination of Oral + Rectal 5-ASA

5-ASA have different formulations for different site of action . Balsalazide is more effective in inducing remission.

Oral 5-ASA , start at low dose , if persistently symptomatic increase to maximum tolerated dose.

5-ASA enema/foam + 5-ASA suppository twice daily

LEFT-SIDED COLITIS, EXTENSIVE COLITIS, AND PANCOLITIS

SUBSEQUENT APPROACH

If no response in 2-4 weeks budesonide-MMX

Failure to respond to budesonide-MMX or severe symptoms oral prednisolone

Prednisolone more effective than sulfasalazine


MAINTAINANCE THERAPY:

ALL PATIENTS REQUIRES

ORAL 5-ASA 3gm/day

5-ASA enema/suppository once/twice daily

Steriod enema should be avoided for maintenance

Budesonide-MMX may be given for 8 weeks


MAINTAINANCE THERAPY:

Glucocorticoids should be tapered OFF after the patient has been stable for two to four weeks. Steroids should be tapered over eight weeks by decreasing the dose by 5 to 10 mg every week until a daily dose of 20 mg is reached, and then by 2.5 mg every week

Rapid reduction early relapse, adrenal insufficiency

STERIOD DEPENDENT UC(10MG>3 MONTHS)


Patients who fail to response are

Alternate or concomitant diagnosis (IBD+IBS)

Non compliance

Persistent symptoms inspite of optimal therapy

STERIOD REFRACTORY ULCERATIVE COLITIS(no clinical respsonse to oral >30day or iv >10 days)

MANAGEMENT OF PERSISTENT SYMPTOMS

Mild intermittent diarrhea without signs of systemic toxicity Loperamide

Abdominal cramping without signs of systemic toxicity dicyclomine, hyoscyamine

Avoid Opiods masks signs and symptoms

Avoid NSAIDS exacerbated IBD

SYMPTOMATIC TREATMENT

Routine health maintenance

Screening and prevention of other diseases

Monitoring for side effects of therapy

IMMUNIZATION



Cancer screening- colorectal, cervical and skin cancer

Osteoporosis screening-postmenopausal, ongoing corticosteroid treatment, cumulative prior use of corticosteroids exceeding three months, history of low-trauma fractures, or age over 60 years

Anxiety/depression screening


Laboratory monitoring

35-90% Iron deficint

Other causes of anemia B12,folic acid,drug induced ( sulfasalazine/thiopurines)

S.Creat ,HCT every 6/12 monthly


Patients with mild to moderate distal colitis may be treated with oral aminosalicylates, topical mesalamine, or topical steroids (Evidence A).

Topical mesalamine agents are superior to topical steroids or oral aminosalicylates (Evidence A).

Th e combination of oral and topical aminosalicylates is more eff ective than either alone (Evidence A).

In patients refractory to oral aminosalicylates or topical corticosteroids, mesalamine enemas or suppositories may still be eff ective (Evidence A)

AGA GUIDELINES

Th e unusual patient who is refractory to all of the above agents in maximal doses, or who is systemically ill, may require treatment with oral prednisone in doses up to 40 60 mg per day, or infl iximab with an induction regimen of 5 mg / kg at weeks 0, 2, and 6, although the latter two agents have not been studied specifi cally in patients with distal disease (Evidence C).

AGA GUIDELINES

Mesalamine suppositories are eff ective in the maintenance of remission in patients with proctitis, whereas mesalamine enemas are eff ective in patients with distal colitis when dosed even as infrequently as every third night (Evidence A). Sulfasalazine, mesalamine compounds, and balsalazide are also eff ective in maintaining remission; the combination of oral and topical mesalamine is more eff ective than either one alone (Evidence A)

AGA GUIDELINES

Topical corticosteroids including budesonide, however, have not proven effective for maintaining remission in distal colitis

When all of these measures fail to maintain remission in distal disease, thiopurines (6-mercaptopurine (6-MP) or azathioprine) and infl iximab (Evidence A), but not corticosteroids, may prove eff ective (Evidence B

AGA GUIDELINES

Patients with mild to moderate extensive colitis should begin therapy with oral sulfasalazine in daily doses titrated up to 4 6 g per day, or an alternate aminosalicylate in doses up to 4.8 g per day of the active 5-aminosalicylate acid (5-ASA) moiety (Evidence A). Oral steroids are generally reserved for patients who are refractory to oral aminosalicylates in combination with topical therapy, or for patients whose symptoms are so troubling as to demand rapid improvement (Evidence B). 6-MP and azathioprine are eff ective for patients who do not respond to oral steroids, and continue to have moderate disease, and are not so acutely ill as to require intravenous therapy (Evidence A).

AGA GUIDELINES

Infl iximab is an eff ective treatment for patients who are steroid refractory or steroid dependent despite adequate doses of a thiopurine, or who are intolerant of these medications. Th e infl iximab induction dose is 5 mg / kg intravenously at weeks 0, 2, and 6 weeks (Evidence A). Infl iximab is contraindicated in patients with active infection, untreated latent TB, preexisting demyelinating disorder or optic neuritis, moderate to severe congestive heart failure, or current or recent malignancies.

AGA GUIDELINES

Once the acute attack is controlled, a maintenance regimen is usually required, especially in patients with extensive or relapsing disease. Sulfasalazine, olsalazine, mesalamine, and balsalazide are all eff ective in reducing relapses (Evidence A). Patients should not be treated chronically with steroids.

AGA GUIDELINES

Azathioprine or 6-MP may be useful as steroid-sparing agents for steroid-dependent patients and for maintenance of remission not adequately sustained by aminosalicylates, and occasionally for patients who are steroid dependent but not acutely ill (Evidence A). Infl iximab is eff ective in maintaining improvement and remission in the patients responding to the infl iximab induction regimen (Evidence A).

AGA GUIDELINES

THANK YOU

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Health & Medicine

ULCERATIVE COLITIS ( MILD TO MODERATE) MANAGEMENT