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 TherapyTop 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 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 VariableFactor No of stools in 1 weekX 2 Abdominal pain each day for 7 daysX 5 General well being, from 0 (well) to 4 (terrible) each day for seven days X 7 Presence of complicationsX 20 Taking Lomitil or opiates for diarrheaX 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 weightX 1

Crohn’s Disease Activity Index Scoring System Mild Disease Moderate Disease 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 DEMOGRAPHICSSTEP UP THERAPYTOP DOWN THERAPY P-VALUE Number of Patients912 Mean Age Gender8 M 1 F8 M 4 F CDAI at Diagnosis

Grouping Step Up TherapyNumber of Patients (9) Mesalamine+6MP4 Mesalamine+ Azathioprine 1 Mesalamine1 Mesalamine+Predniso ne 1 Budesonide+Azathiop rine 2 Top Down TherapyNumber of Patients (12) Infliximab + Mesalamine 7 Infliximab Monotherapy 3 Adalimumab2

Results PRIMARY END POINT STEP UP THERAPYTOP DOWN THERAPY P-VALUE Mean CDAI at Diagnosis Mean CDAI at 4 Weeks Mean CDAI at 24 Weeks Mean CDAI at 52 Weeks Total Number of Patients with Remission at 4 Weeks 1/99/

Primary End Point

Results SECONDARY END POINTS STEP UP THERAPYTOP DOWN THERAPY P-VALUE Complications of Disease on Therapy 6/92/ Side Effects on Therapy 4/90/ Relapse Rate on Therapy 8/94/ Surgeries3/92/ Hospitalizations7/95/ Steroid Dependence 5/90/

Complications of Disease on Therapy Complication of Crohn’s Disease Step Up Therapy (6)Top Down Therapy (2) Bowel Obstruction21 Stricture11 Peri-anal Abscess20 Extra-Intestinal Manifestations10

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

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