Asymptomatic UC patients on an immunomodulator with
persistent moderate mucosal inflammation should either add a
biologic or switch to a biologic
William J. Sandborn, MD
Professor & Chief, Division of Gastroenterology
Director, UCSD IBD Center
Arguments for treating to target in
ulcerative colitis
• It is feasible
• It is associated with a reduced rate of colectomy and an
increased rate of steroid-free remission
• It is associated with a reduced rate of colorectal dysplasia
and cancer
• It is logical and obviously the right thing to do
It is feasible:
Treating to target in ulcerative colitis
Treat-to-Target Algorithm
)
CRP, C-reactive protein.
Bouguen G, Levesque BG, Sandborn WJ. Clin Gastroenterol Hepatol. 2014 (In Press)
Study population
UCSD IBD Center
144 patients
No endoscopy
31 patients
Only one endoscopy
53 patients
At least 2 consecutive
assessments
60 patients
Bougen G, Levesque B,
Sandborn W.
Inflam Bowel Dis
2014 (In Press)
STUDY
POPULATION
No inflammation at baseline
15 patients
INFLAMMATION AT BASELINE
45 patients
Endoscopic procedures
Endoscopy 1
Median
time
19 weeks
Endoscopy 2
Median
time
17 weeks
Endoscopy 3
Median
time
20 weeks
median follow-up of 76 weeks
(IQR75 54-92)
• 159 endoscopic procedures
92 colonoscopy
67 flexible sigmoidoscopy
• 60 patients had at least 2 consecutive
endoscopic procedures
• 26 patients (43%): 3 consecutive procedures
• 8 patients (13%): 4 consecutive procedures
• 2 patients (3%): 5 consecutive procedures
Endoscopy 4
Bougen G, Levesque B, Sandborn W.
Inflam Bowel Dis 2014 (In Press)
Adjustment in medical therapy and surgery
MEDIAN FOLLOW-UP = 76 weeks (IQR75 44-79)
MEDIAN TIME BETWEEN PROCEDURE = 25 weeks (16-42)
• Overall cohort :
5-ASA introduction: 2 events
5-ASA increase dose: 6 events
Oral steroids introduction: 11 events
Anti-TNF Introduction: 20 events
Anti-TNF Optimization/switch: 11 events
Immunosuppression introduction: 18 patients
• Surgery: 7 patients
Bougen G, Levesque B, Sandborn W.
Inflam Bowel Dis 2014 (In Press)
Cumulative probability of reaching mucosal healing and
histologic healing
Bougen G, Levesque B, Sandborn W.
Inflam Bowel Dis 2014 (In Press)
Reaching mucosal healing according to medical management
during follow up multivariate analysis: adjustments in medical
therapy
Bougen G, Levesque B, Sandborn W.
Inflam Bowel Dis 2014 (In Press)
It is associated with a reduced rate
of colectomy and an increased rate
of steroid-free remission
Mucosal Healing after treatment as predictor of
subsequent disease course in ulcerative colitis
Pts with MH at 1 year
p=0.02
Pts without MH at 1 year
Frøslie KF, et al. Gastroenterology. 2007;133:412-422.
Mucosal Healing and Time to Colectomy in Infliximabtreated Patients: Endoscopy Subscore
0 = NORMAL
1 = MILD
2 = MODERATE
Colombel JF, Sandborn WJ, et al. Gastroenterology 2011;141:1194-1201.
3 = SEVERE
Association Between Week 8 Mayo Endoscopy Subscore and and Corticosteroid-Free Symptomatic
Remission at Week 30 During Anti-TNF Antibody
Therapy
Week 8 Mayo
endoscopy sub-score
Corticosteroid-free
symptomatic
remission, %
P value
0
46
< 0.001
1
34
2
11
3
6.5
Colombel JF, Sandborn WJ. Gastroenterology 2011
It is associated with a reduced rate
of colorectal dysplasia and cancer
Odds ratio for colorectal
cancer (95% CI)
Predicting cancer risk in UC
12
P<0.001
10
8
6
P=0.001
OR=5.13
4
Disease extent
PSC
Disease duration
Family history of
CRC
OR=2.54
2
0
Colonoscopy
inflammation score
Histological
inflammation score
OR for each 1 point increase
in inflammatory score
Rutter et al Gastroenterology 2004;126:451
It is logical and obviously the right
thing to do
Parachute use to prevent death and major trauma
related to gravitational challenge: a systematic review
of randomized controlled trials
• Objectives: To determine whether parachutes are effective
in preventing major trauma related to gravitational
challenge
• Design: Systematic review of randomized controlled trials
• Data sources: Medline, Web of Science, Embase, and the
Cochrane Library databases; appropriate internet sites and
citation lists
• Study selection: Studies showing the effects of using a
parachute during free fall
• Main outcome measure: Death or major trauma, defined as
an injury severity score > 15
Gordon CS. BMJ 2003
Parachute use to prevent death and major trauma
related to gravitational challenge: a systematic review
of randomized controlled trials
• Results: We were unable to identify any randomized
controlled trials of parachute intervention
• Conclusions: As with many interventions intended to
prevent ill health, the effectiveness of parachutes has not
been subjected to rigorous evaluation by using randomized
controlled trials. Advocates of evidence based medicine
have criticized the adoption of interventions evaluated by
using only observational data. We think that everyone
might benefit if the most radical protagonists of evidence
based medicine organized and participated in a double
blind, randomized, placebo controlled, crossover trial of the
parachute
Gordon CS. BMJ 2003
It is logical and obviously the right
thing to do
• You don’t need a randomized controlled trial
to determine that using a parachute is the
right thing to do
• Do you need a randomized controlled trial to
determine that healing the colon is the right
thing to do?
Treating to Mucosal Healing in
Ulcerative Colitis
• It is feasible
• It is associated with a reduced rate of
colectomy and an increased rate of steroidfree remission
• It is associated with a reduced rate of
colorectal dysplasia and cancer
• It is logical and obviously the right thing to
do