topamax 600 mg

PIANO Interim Reports – 2013

Report April 2013

PIANO: PREGNANCY IN INFLAMMATORY BOWEL DISEASE AND NEONATAL OUTCOMES

 

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.  

 

Update April 2013:

Currently enrollment is ongoing but limited to pregnant women on biologic +/- immunomodulator therapy.  There are 1226 patients in the registry of which 397 have rolled over into the 4 year extension (once the infant has reached 1 year of age) and 934 remain active.

Analysis of 896 of 1044 women in PIANO who had delivered as of April 25, 2012 was recently presented at Digestive Diseases Week.11  Patients were divided into 4 groups based on medication use during pregnancy and the 3 months prior to the last menstrual period: Unexposed (n= 326), AZA/6MP (n=204), Biologics (n= 291) and combination biologic and AZA/6MP (n=75). Overall, there was a 4% rate of SAB; 11% rate of PTB, 7% rate of LBW, 5.9% rate of congenital anomalies and a 44% rate of cesarean section. Additionally there was a 12% rate of NICU stay for the infant. When assessed by drug exposure, there was no increase in congenital anomalies, LBW, and NICU stay by drug exposure.  However, there was a significant increase in complications in the combination therapy group.  Overall, there was an increase in preterm birth [RR 1.83 (1.01-3.31)] among all IBD patients on combination therapy.  When looked at by disease type, patients with CD did not have an increase in any complication by drug exposure.  However, UC patients had an increase in spontaneous abortions in the biologic group and in the combination therapy group had an increase in any complication, PTB, LBW, and NICU stays.  While these outcomes were controlled for disease activity in the analysis, UC patients did have statistically more active disease than patients with CD overall (p <0.01).  Unmeasured variables for disease activity such as malnutrition, anemia and the continuation of therapy in the patient with minimal response to avoid surgery during pregnancy may be playing a role in these increased adverse outcomes in the UC patient.

In the first year of life, there was no difference in height and weight or achievement of developmental milestones at months 4, 9, and 12 by drug exposure when adjusted for maternal age and disease activity.  There was also no increase in neonatal infections.  However, when biologics were removed one at a time from the analysis, there was a significant increase in infections at one year in the combination therapy group relative to the unexposed group when certolizumab was removed from the biologic group [RR 1.35 (1.01-1.80)].  This was not seen when infliximab or adalimumab were removed. Given the known lack of placental transfer for certolizumab compared to infliximab and adalimumab, this suggests a role for the biologic agent in combination with the immunomodulator in these infant infections.  Reassuringly, the majority of the infections were minor, such as otitis media and upper respiratory infections. 75% of women reported breastfeeding.  Unexposed women were more likely to breastfeed (85%) than exposed (AZA: 65%, Biologics: 71%, Combination 61%) p<.0001.  When controlled for drug exposure, breastfeeding was not associated with infection risk or height and weight deficiencies. A SRA has been submitted to CCFA for funding starting June 2013.

 

 List of Publications

  1. 1)    Placental Transfer of Anti-Tumor Necrosis Factor Agents in Pregnant Patients With Inflammatory Bowel Disease. Mahadevan U, Wolf DC, Dubinsky M, Cortot A, Lee SD, Siegel CA, Ullman T, Glover S, Valentine JF, Rubin DT, Miller J, Abreu MT. Clin Gastroenterol Hepatol. 2013 Mar;11(3):286-92.
  2. Abstract presented as an oral presentation at DDW in 2009, 2010, 2012, 2013
    • DDW 2013 Oral Presentation: Prospective Evaluation of Adherence to Health-care Maintenance in Women with Inflammatory Bowel Disease  Sheibani, Sarah; Martin, Chris; Bloomfeld, Richard; Isaacs, Kim; Saha, Sumona; Mahadevan, Uma