Clinical Guidelines for the Medical Management of LeftSided Ulcerative Colitis and Ulcerative Procti

1
Clinical Guidelines for the Medical Management of
Left-Sided Ulcerative Colitis and Ulcerative
Proctitis

• Miguel Regueiro, MD, Edward V. Loftus, Jr, MD, A.
  Hillary Steinhart, MD, and Russell D. Cohen, MD,
  FACG, AGAF
• Inflamm Bowel Dis, Volume 12, Number 10, October
  2006

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Ulcerative Colitis and ProctitisBackground

• UC incidence 2.2-14.3/100,000 person years in
  North America1
• UC usually presents with disease limited to the
  distal or left colon1,2
• left-sided UC (L-UC) disease distal to the
  splenic flexure
• ulcerative proctitis (UP) limited to the rectum
• ulcerative proctosigmoiditis (UPS) limited to
  rectosigmoid

1) Loftus EV. Gastroenterology 20041261504-1517
2) Langholz E. Dan Med Bull 1999 46 400-415.
3
Why L-UC Matters?

• L-UC generally amenable to rectally administered
  (topical) therapy
• Topical therapy works more effectively1-3 and
  more rapidly3 than oral
• Emerging data suggest that early, aggressive
  treatment of UC may prevent or delay proximal
  extension4

1) Gionchetti P, Rizzello F, Venturi A, et al.
Dis Colon Rectum 1998 41 93-97. 2) Safdi M,
DeMicco M, Sninsky C, et al. Am J Gastroenterol
1997 92 1867-1871. 3) Kam L, Cohen H, Dooley
C, Rubin P, Orchard J. Am J Gastroenterol 1996
91 1338-42 4) Pica R, Paoluzi OA, Iacopini F,
et al. Inflamm Bowel Dis 2004 10 731-736.
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Treatment of Active UP

• Topical therapy preferred treatment
• Corticosteroids and5-ASAs available in many
  forms
• suppositories reach the upper rectum
• enemas reach splenic flexure and the distal
  transverse colon

Proximal distribution of topical preparations
Adapted with permission from Marshall JK, Irvine
EJ. Am J Gastroenterol 2000 95 1628-1636.
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Treatment of Active UP

• 5-ASA suppositories first-line therapy1
• highly effective
• well-tolerated
• Topical 5-ASAs superior to topical
  corticosteroids in randomized trials2-6
• For patients intolerant of or unresponsive to
  topical 5-ASA, topical corticosteroids are an
  alternative1

1) Regueiro M, Loftus EV Jr, Steinhart AH, Cohen
RD Inflammatory Bowel Disease Center. Inflamm
Bowel Dis. 2006. 10972-8. 2) Mulder CJ et al.
Eur J Gastroenterol Hepatol 1996 8 549-53. 3)
Lemann M et al. Aliment Pharmacol Ther 1995 9
557-562. 4) Gionchetti P et al. J Clin
Gastroenterol 2005 39 291-297. 5) Lucidarme D
et al. Aliment Pharmacol Ther 1997 11 335-340.
6) Farup PG et al. Scand J Gastroenterol 1995
30 164-70.
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UP Management Algorithm
Confirmed ulcerative proctitis (symptoms
endoscopic evidence of mucosal Inflammation not
extending above the rectum)
Rectal (topical )5-ASA 1 g/d as suppository
(1st Line) 5-ASA 1 4 g/d is also effective as
liquid enema or foam
CLINICAL RESPONSE
NO RESPONSE
Consider Maintenance Therapy Rectal 5-ASA
suppositories (500 1000 mg) 3 times weekly or
every second day
Add Oral 5-ASA (2.4 4.8 g/d) and/or rectal
corticosteroid therapy as suppository, enema or
foam
Frequent / repeated flares
Increase maintenance suppository therapy to
daily OR Oral 5-ASA 2-4 g/d
Colonoscopy to examine for proximal disease
progression beyond rectum Treat for Refractory
Disease as described elsewhere
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Treatment of Active L-UC

• Topical 5-ASAs effective for active L-UC
• Topical corticosteroids effective alternative for
  patients intolerant of or unresponsive to 5-ASAs
• Combination therapy for patients without adequate
  response to topical monotherapy
• topical 5-ASA and topical corticosteroid, or
• oral and topical 5-ASAs
• Oral corticosteroids reserved for patients not
  responding to topical therapies and/or
  oral5-ASAs

1) Mulder CJ et al. Eur J Gastroenterol Hepatol
1996 8 549-53. 2) Safdi M et al. Am J
Gastroenterol 1997 92 1867-1871. 3) Rizzello F
et al. Aliment Pharmacol Ther 2002 16
1109-1116. 4) Marteau P et al. Gut 2005 54
960-965.
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L-UC Management Algorithm
Confirmed left-sided ulcerative colitis (symptoms
endoscopic evidence of mucosal inflammation
extending beyond the rectum but not extending
above the splenic flexure (approximately 60cm))
Consider adding
Rectal (topical) 5-ASA 1-4 g/d as a liquid enema
(foam or gel may be used if PS)
Oral 5-ASA 2.4 to 4.8 g/d, or equivalent
Clinical Response
Insufficient Response
Worsening

• Stop 5-ASA.
• Start hydrocortisone liquid enema 100 mg qhs. (if
  PS, can use hydrocortisone acetate foam 10
  qd-bid)

See Maintenance Algorithm
Insufficient Response
Add oral prednisone 40 mg/d or equivalent
Clinical Response
Insufficient Response
See Refractory UC Algorithm
PS proctosigmoiditis inflammation limited to
rectum and sigmoid.
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Maintenance of Remission

• UP
• Topical 5-ASAs preferred maintenance medication
• L-UC
• Topical 5-ASA maintains remission in most
  patients1-3
• Patients achieving remission with combination
  oral/topical 5-ASA therapy should continue
  combined therapy for maintenance4
• Oral 5-ASA effective alternative to topical for
  maintenance
• No role for oral corticosteroids in maintenance

1) Hanauer SB et al. Am J Gastroenterol 2000 95
1749-1754. 2) Marteau P et al.Gut 1998 42
195-199. 3) DAlbasio G et al. Dis Colon Rectum
1990 44 394-7. 4) SAlbasio G. et al. Am J
Gastroenterol 1997 92 1143-1147.
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L-UC Maintenance Algorithm
Response or Remission Successfully Induced by
Following Agent
Change to
Intravenous Corticosteroids
Oral Corticosteroids
Topical Corticosteroids
Change to

• Add mesalamine or corticosteroid enemas (if PS,
  can use foam or gel) AND maximum dose of oral
  5-ASA.
• Taper prednisone

Consider adding
Relapse
5-ASA enema (foam or gel if PS)
Oral 5-ASA 1.6 to 4.8 g/d, or equivalent
See Refractory UC Algorithm
Continue 5-ASA agents indefinitely
Relapse
Long-term maintenance

• Patient may prefer to taper off either oral or
  rectal agent.
• Oral 5-ASA enemas dosed twice weekly effective
  in some patients.

See Induction Algorithm
PS proctosigmoiditis inflammation limited to
rectum and sigmoid.
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Refractory UP and L-UC

• Induction of remission
• Infliximab1-4
• Cyclosporine effective for acute management5-7
• toxicity limits its long-term use
• For patients failing proven regimens
• Nicotine and/or antibiotics may be tried
• Surgery may ultimately be necessary
• Maintenance of remission
• Azathioprine/ 6-mercaptopurine, infliximab may be
  required in corticosteroid dependent disease

1) Sands BE et al. Inflammatory Bowel Diseases
20017(2)83-88. 2) Probert CS et al. Gut
200352998-1002. 3) Jarnerot G et al.
Gastroenterology 20051281805-1811. 4) Regueiro
M et al. J Clin Gastroenterol. 2006
Jul40(6)476-81. 5) Sandborn W. Inflamm Bowel
Dis 1995148-63. 6) Cohen R et al. Am J
Gastroenterol 1999941587-92. 7) Lichtiger S et
al. N Engl J Med 19943301841-5.  
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Refractory UP/L-UC Algorithm
Review medication compliance Exclude concomitant
NSAID use
See Maintenance Algorithm
Response
No response
Trial of 5-aminosalicylate cessation and
re-challenge (exclude hypersensitivity)
No response
Colonoscopy with biopsies Stool C. difficile
toxin and bacterial culture (Exclude proximal
extension, Crohns disease, and viral/bacterial
superinfection)
Response
No response
?
?
Azathioprine 2-2.5 mg/kg daily or
6-mercaptopurine 1-1.5 mg/kg daily
Ciprofloxacin/ metronidazole (efficacy not
established)
Transdermal nicotine (ex-smokers)
No response
No response
No response
Infliximab 5 mg/kg IV induction (0, 2, 6 weeks)
Response
No response
Response
Discontinue after 1-2 mos. If relapse continue as
maintenance.
Infliximab 5 mg/kg IV every 8 weeks
Surgery