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