Transcript GUIDELINES FOR COLORECTAL SCREENING IN HIGH RISK …

Medical Management
of
Ulcerative Colitis
Conrad Beckett
Bradford Royal Infirmary
M62 Course
March 2006
Aims of medical therapy
• Treat acute attacks
• Maintain remission
What is the evidence base?
What’s new?
Treatment options
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5-Aminosalicylates
Steroids
Azathioprine
Cyclosporin
Infliximab
New therapies
Topical Therapy
• 5-ASA vs. steroid enemas
• Effective in inducing remission (1).
• 5-ASA more effective than topical steroids
(2).
• Cyclosporin enemas used in resistant
proctitis.
Oral 5-ASA
• 5-ASA are effective in the induction and
maintenance of remission in UC (3)[Grade A].
• ASCEND 11 found that 4.8g/day is better than
2.4g/day in treating moderately active UC (4).
• Paoluzi et al. found that 2.4g/day no more
effective in preventing recurrence than 1.2g/day
(5).
Oral 5-ASA (2)
• Adherence to therapy vital to emphasize as
x5 increase in relapse rate when compliance
<80% (6).
• Adding topical 5-ASA to oral 5-ASA
therapy can also help in frequently
relapsing disease (7).
Oral 5-ASA (3)
• Regular 5-ASA may reduce risk of
colorectal cancer in patients with UC (8).
• The case-control study found that 5-ASA
use reduced CRC risk by 81%.
• Regular hospital visits also reduced risk.
• A family history of sporadic CRC increased
risk five fold.
• May help with patient compliance.
Steroids
• Remain standard therapy for inducing
remission in moderate/severe UC [grade A].
• Trials conducted >40 years ago (10,11).
• No evidence to support their use in
maintenance of remission [grade A].
• ? Any benefit from more than 40mg (12).
Azathioprine
• Until recently, relatively weak Grade C evidence
(13,14).
• The azathioprine withdrawal study provided
stronger evidence (15) [Grade A].
• A recent study by Ardizzone has strengthened the
evidence for its use in inducing remission of
steroid dependent UC (16).
• 53% vs. 21% in remission and steroid free at 6/12
when compared to 5-ASA.
Cyclosporin
• No RCT data.
• Use based on the Lichtiger study where
75% short-term response in severe UC (18).
• At best, 55% avoid surgery at 3 years.
• Significant side-effect profile.
• Lower dose, 2mg/kg may be better tolerated
(19).
Infliximab
• ACT 1&2 have demonstrated its efficacy in the
induction and maintenance of remission in UC
(Rutgeerts et al. NEJM 2005;353:2462-76).
• Significantly better than placebo in inducing and
maintaining remission in moderate to severe UC.
• Sig. more treated patients were able to achieve
steroid free remission.
• Improved quality of life scores.
Infliximab (2)
• Also studied as a single infusion as rescue
therapy in acute severe UC (20).
• Significantly fewer patients in the
Infliximab treated group had a colectomy
(29% vs. 67%).
• No serious side-effects.
• Follow-up only 3 months.
Infliximab vs. Cyclosporin
• No trial evidence as to which to use first as
rescue therapy when IV steroids fail.
• Both have a significant side-effect profile.
• Infliximab is a simpler single infusion.
• No long-term data on Infliximab in UC.
• Neither increase surgical complications.
• Half-life of Infliximab >> CyA.
Treatment algorithm for UC
Moderate
Severe
Acute Severe
5 ASA
dependent
Oral Steroids
refractory
Cyclosporin
Infliximab
AZA
IV Steroids
Colectomy
Infliximab
ACT patients
Remission
Jarnerot patients
Rescue
When to intervene?
• The Oxford study demonstrated that at day
3 of IV hydrocortisone, if
BO x 8/day
BO x 3-8 with CRP>45mg/l
• 85% would require colectomy.
• If > 3 stools (with blood) a day at day 7,
there was a 60% chance of continuous
symptoms and 40% chance of colectomy.
Summary
• High dose 5-ASA more effective in inducing
remission in moderate UC.
• 5-ASA compliance vital in maintaining remission.
• 5-ASA may have a role in reducing CRC risk.
• Strengthening evidence for Azathioprine.
• Consider Infliximab or Cyclosporin promptly as
rescue therapy when no response to IV steroids.
• JOINT CARE! As surgery will be the best
treatment for some patients.