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.
Assessment of clinical severity
Assessment of clinical severity
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
TREATMENT OF ULCERATIVE PROCTITIS OR PROCTOSIGMOIDITIS
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
TREATMENT OF ULCERATIVE PROCTITIS OR PROCTOSIGMOIDITIS
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
TREATMENT OF ULCERATIVE PROCTITIS OR PROCTOSIGMOIDITIS
Maintainance :
not recommended in patients with a first episode of mild ulcerative proctitis that has promptly responded to treatment
TREATMENT OF ULCERATIVE PROCTITIS OR PROCTOSIGMOIDITIS
MAINTAINANCE TREATMENT recommended in:
Relapse more than once a year
Proctosigmoiditis
Discontinuation for the above patients if remission is more than 2 years
TREATMENT OF ULCERATIVE PROCTITIS OR PROCTOSIGMOIDITIS
Maintainance regimen:
Proctitis: once daily 5-ASA suppository
Proctosigmoiditis : once daily 5-ASA enema
TREATMENT OF ULCERATIVE PROCTITIS OR PROCTOSIGMOIDITIS
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
LEFT-SIDED COLITIS, EXTENSIVE COLITIS, AND PANCOLITIS
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
LEFT-SIDED COLITIS, EXTENSIVE COLITIS, AND PANCOLITIS
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)
LEFT-SIDED COLITIS, EXTENSIVE COLITIS, AND PANCOLITIS
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
OTHER MANAGEMENT ISSUES
OTHER MANAGEMENT ISSUES
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
OTHER MANAGEMENT ISSUES
Laboratory monitoring
35-90% Iron deficint
Other causes of anemia B12,folic acid,drug induced ( sulfasalazine/thiopurines)
S.Creat ,HCT every 6/12 monthly
OTHER MANAGEMENT ISSUES
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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