Top Down Therapy vs Step Up
Therapy in Pediatric Patients
with new onset Crohn’s Disease
Presenters
Dr Ali Minhas M.B.B.S
Dr Orooj Khan M.B.B.S
Mentor
Dr Maya D Srivastava M.D
Background
• Top-down (TD) therapy with tumor necrosis
factor inhibitors early in disease course of
adult Crohn's disease (CD) has been shown to
result in decreased steroid dependence,
hospitalizations, complications, and disease
activity compared to conventional step-up
(SU) therapy
Background
• Anti-TNF is effective in pediatric patients with
CD failing conventional step up therapy
• Data regarding Top Down therapy in pediatric
patients is limited
Introduction
Aim
• To compare top down therapy with step up
therapy in relation to achieving early
remission and prevention of known disease
complications in pediatric patients with new
onset Crohn’s Disease
Introduction
Top Down Therapy
• Inclusion of biologic agents as initiation therapy
to alter the course of Crohn’s disease
Step Up Therapy
• Use of least efficacious to most potent agents in a
step wise fashion to alter the course of Crohn’s
Disease
Crohn’s Disease Management
Pyramids
Step Up Therapy
Top Down Therapy
Study Design
• Retrospective chart review of all pediatric
patients (age under 18) with CD in an
outpatient solo practice
• Charts reviewed dated from 2007-2009
• 89 charts identified by diagnostic billing codes
for CD (555.0, 555.1, 555.2)
• 21 patients satisfied the inclusion criteria and
all were included in the study
Study Design
• Crohn’s Disease Activity Index (CDAI) used to
calculate the severity of CD
• Data analysis conducted by using unpaired t
test and Fischer’s exact test
• IRB exempt
Crohn’s Disease Activity Index
Variable
Factor
No of stools in 1 week
X2
Abdominal pain each day for 7 days
X5
General well being, from 0 (well) to 4 (terrible) each day for
seven days
X7
Presence of complications
X 20
Taking Lomitil or opiates for diarrhea
X 30
Presence of an abdominal mass (0 as none, 2 as
questionable, 5 as definite)
X 10
Absolute deviation of Hematocrit from 47% in men and 42% X 6
in women
Percentage deviation from standard weight
X1
Crohn’s Disease Activity Index
Scoring System
• Mild Disease
150-199
• Moderate Disease 200-449
• Severe Disease
>450
• Remission
<150
INCLUSION CRITERIA
New Diagnosis of Crohn’s Disease with in 1 year
Age between 6 –18 years
Patients on Biologic agents on the onset of diagnosis
Patients on step up therapy on the onset of diagnosis
CDAI index of at least 200 at diagnosis
EXCLUSION CRITERIA
Patients with established diagnosis prior to 2007
Patients with CDAI < 150
PRIMARY END POINT
Remission at 4, 24 and 52 weeks after initiation of either therapy as calculated by CDAI
SECONDARY END POINTS
Complications of Crohn’s Disease in the past 1 year
Side effects in the past 1 year
Number of relapses in the past 1 year
Steroid use
Baseline Demographics
DEMOGRAPHICS
STEP UP THERAPY
TOP DOWN
THERAPY
P-VALUE
Number of Patients
9
12
Mean Age
14.00
15.00
0.4729
Gender
8M1F
8M4F
0.3383
CDAI at Diagnosis
247
265
0.5689
Grouping
Step Up Therapy
Number of
Patients (9)
Top Down Therapy
Number of
Patients (12)
Mesalamine+6MP
4
Infliximab +
Mesalamine
7
Mesalamine+
Azathioprine
1
Infliximab
Monotherapy
3
Mesalamine
1
Mesalamine+Predniso
ne
1
Adalimumab
2
Budesonide+Azathiop 2
rine
Results
PRIMARY END
POINT
STEP UP THERAPY
TOP DOWN
THERAPY
P-VALUE
Mean CDAI at
Diagnosis
247
265
0.5689
Mean CDAI at 4
Weeks
163
118
0.0242
Mean CDAI at 24
Weeks
115
82
0.0831
Mean CDAI at 52
Weeks
117
83
0.0783
Total Number of
Patients with
Remission at 4
Weeks
1/9
9/12
0.0075
Primary End Point
Primary End Point
Results
SECONDARY END
POINTS
STEP UP THERAPY
TOP DOWN
THERAPY
P-VALUE
Complications of
Disease on Therapy
6/9
2/12
0.0318
Side Effects on
Therapy
4/9
0/12
0.0211
Relapse Rate on
Therapy
8/9
4/12
0.0244
Surgeries
3/9
2/12
1.000
Hospitalizations
7/9
5/12
0.1842
Steroid
Dependence
5/9
0/12
0.0062
Complications of Disease on
Therapy
Complication of Crohn’s
Disease
Step Up Therapy (6)
Top Down Therapy (2)
Bowel Obstruction
2
1
Stricture
1
1
Peri-anal Abscess
2
0
Extra-Intestinal Manifestations
1
0
Secondary End Points
Conclusions
• TD strategy is more effective in rapidly gaining
and maintaining control in the first year of
diagnosis in pediatric patients with new onset
Crohn’s disease
• TD therapy associated with decreased
complications of disease, relapses and steroid
dependence in the first year of diagnosis
Conclusions
• Almost all patients on step up therapy
relapsed in the first year and required antiTNF salvage
Study Evaluation
• Small sample size
• Retrospective study
• Insurance Approval Barriers
Thank You