top down therapy vs step up therapy in pediatric patients with new onset crohn’s disease...
TRANSCRIPT
Top Down Therapy vs Step Up Therapy in Pediatric Patients
with new onset Crohn’s Disease
PresentersDr Ali Minhas M.B.B.SDr Orooj Khan M.B.B.S
MentorDr 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 IndexVariable Factor
No of stools in 1 week X 2
Abdominal pain each day for 7 days X 5
General well being, from 0 (well) to 4 (terrible) each day for seven days
X 7
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% in women
X 6
Percentage deviation from standard weight X 1
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 8 M 1 F 8 M 4 F 0.3383
CDAI at Diagnosis 247 265 0.5689
Grouping Step Up Therapy Number of
Patients (9)
Mesalamine+6MP 4
Mesalamine+ Azathioprine
1
Mesalamine 1
Mesalamine+Prednisone
1
Budesonide+Azathioprine
2
Top Down Therapy Number of Patients (12)
Infliximab + Mesalamine
7
Infliximab Monotherapy
3
Adalimumab 2
ResultsPRIMARY 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
ResultsSECONDARY 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 anti-TNF salvage
Study Evaluation
• Small sample size
• Retrospective study
• Insurance Approval Barriers
Thank You