topamax 600 mg

PIANO Interim Reports – 2011

Report November 2011

PIANO: PREGNANCY IN INFLAMMATORY BOWEL DISEASE AND NEONATAL OUTCOMES

Year 5 Progress Report

 

II. Overall Objectives and Specific Aims: Unchanged from original Proposal

 

Hypothesis

Women with IBD exposed to azathioprine/6-mp and anti-TNF therapies during pregnancy and conception have different pregnancy outcomes than women with IBD not exposed to these medications.  

 

Primary Objective

  • Determine whether the rates of congenital malformations, spontaneous abortion, preterm birth and small for gestational age (SGA) infants in a prospective national sample of women from the United States with IBD exposed to azathioprine/6MP or anti-TNF therapy are greater than those among IBD-affected women not exposed to these medications
  • Determine 4 year outcomes of infants born to mothers with IBD with respect to developmental delay, infections and other health related complications

 

Secondary Objectives

  • Determine whether the rate of any adverse pregnancy outcomes (defined below) in a prospective national sample of women from the United States with IBD differ with respect to exposure to azathioprine/6MP or anti-TNF therapy
  • Determine factors that predict adverse pregnancy outcomes in a prospective national sample of women from the United States with IBD
  • Determine rates of disease activity during pregnancy and the post-partum in a prospective national sample of women from the United States with IBD
  • Determine whether adverse outcomes are more common when the expectant mother has active IBD than when the expectant mother has quiescent IBD
  • Determine the rate of neonatal complications (defined below) up to one year from birth in a prospective national sample of children born to women from the United States with IBD

 

III. Concise description of the results

  • This project received approval from the CCFA in late January of 2007.  Institutional review board (IRB) approval was obtained from the University of California, San Francisco by July 2007.
  • At this time 31 sites have received IRB approval and have been contracted to participate in this study
  • As of October 27, 2011, 1040 patients have been enrolled in the registry
  • 130 patients have enrolled in the PIANO extention
  • Along with the data monitoring center at the University of North Carolina, case report forms have been continually upgraded as the various sites proceeded through the multiple questionnaires.  A sophisticated website for data entry has been created that can be accessed on-line by each study site.  We have created programs that send automated reminders to each site for when each individual patient questionnaire is due.  We have had excellent compliance with less than 2% of the forms being delinquent
  • Patients who have delivered are eligible for the extension with questionnaires at infant years 1, 2 ,3 and 4.  In addition to maternal and infant health questionnaires, Ages and Stages developmental questionnaires are filled out as well.

 

IV. List of Publications

  1. Abstract presented as an oral presentation at DDW in 2009, 2010
  2. Planned abstract submission of 1000 patient cohort to DDW 2012
  3. This study will generate multiple papers. All contributors will be on at least one publication from this.

 

V. Changes for 2011

a. It has been difficult to get patients at individual sites to continue into PIANO-2 (the 3 year extension) for multiple factors

b. To combat this, sites now continue to follow patients

i. Conference calls with site coordinators done and most sites are nearly ready to start

ii. Payment will be $50 per questionnaire x 3 questionnaires

iii. Year 1 (end of PIANO-1, start of PIANO-2) will be the same as before with the addition of 3 new forms

1. Health care maintenance

2. Socioeconomic if not done before

iv. Ages and Stages

1. New web based form for developmental milestones

2. Mother can go on line and fill out Ages and Stages themselves or coordinator can do it. Form must be done within particular window

a. 24 months – between 23 months and 25 months 15 days

b. 36 months – between 34 months 16 days and 39 months

c. 48 months – between 45 months and 51 months

3. main coordinator will monitor for abnormal scores

v. UNC has opened up web portal to all sites for PIANO-2. At Year 1 you will have the option to click whether patient will continue or not.

vi. Yelena Idomsky will train all site coordinators on PIANO-2.

1. You will get a status update of all patients from your site

2. Patients can be brought back in at any point including Year 4.

 

VI. Interim Analysis

a. 860 women enrolled, 73 withdrew (twins, lost to follow up, no longer wanted to participate). If withdrew before completion of pregnancy will be dropped form study

b. Group A (azathioprine/6mp) n= 152; Group B (biologics) n = 208; Group AB (both) n= 55; Unexposed (to aza/biologics) n = 252

c. Overall minimal differences between Group A, B, AB and unexposed group, except:

i. Increased risk of any complications Group AB: OR 2.60 (1.35-5.00)

ii. Increased risk of preterm birth Group AB: OR 3.42 (1.59-7.37)

iii. Trend towards reduce milestones reached at month 9 Group A: (p=.08)

iv. No increase in infections or birth defects to date by medication exposure