Current Research Initiative Successes

MICROBIOME INITIATIVE:

7 active projects, 12 completed manuscripts in 1.5 years. Their key findings so far:

  • People carrying different IBD genes, such as NOD 2, have different compositions of gut bacteria.  A person’s genes can therefore affect which gut bacteria they host.
  • Different subsets of IBD can be characterized by signature bacterial compositions, defined by risk signature of ~20 microbial families
  • A novel way to study intestinal bacterial metabolism in humans have been identified

Ultimate goals for the consortium-

  • Understand mechanisms by which bacteria, viruses and fungi cause disease in genetically susceptible hosts.  This can lead to new strategies to treat and prevent IBD
  • Identify bacteria and viruses associated with flares:  This will help guide ways to prevent disease relapses by immunization, antibiotics, dietary modification, probiotics, etc.
  • Use bacterial profiles to predict the course of disease in an individual patient with IBD – aggressiveness of disease, risk of complications and response to treatment

PEDIATRIC RISK STUDY:

Enrollment is completed. 1741 pediatric patients enrolled from 28 centers across US and Canadian Center.

  • 1,070 or 70% subjects with confirmed Crohn’s disease (CD)
  • 15% ulcerative colitis (UC)
  • 10% non IBD and
  • about 5% of subjects with (IBD-U) not classified as CD or UC. 

Key findings of the group thus far:

  • 17 genes are expressed differently in intestines of patients who developed a stricture. The group is developing a model for the expression of these genes to be used as predictors of risk for stricture development
  • Children diagnosed under 10 years of age have distinct blood profile antibodies in their blood. These results suggest that there are distinct mechanisms of CD in patients < 10 years

Primary goal-

        Develop a risk model to predict the prognosis and response to therapy of newly diagnosed patients with Crohn’s disease based on their genetic, immunologic, microbial and clinical profiles

GENETICS INITIATIVE: New project, launching this fall.

163 genes associated with IBD have been discovered, but their functions are unknown.

Goals-

  • Understand the function of these genes in normal and IBD patients
  • Group patients into clinically relevant subtypes based on their genetic makeup
  • Find gene pathways that will form good targets for design of new drugs to treat IBD
  • Understand how IBD-associated genes increase risk of developing disease – this information can be used to develop strategies to prevent disease

 CCFA PARTNERS: Internet-based registry of patient reported disease outcomes

  • ~1200 adult patients have signed up and completed the survey
  • Pediatric survey will be launched this fall
  • Questions on drug usage, diet, environment, quality of life and alternative medicines
  • Regular interaction and follow up with patients – reminders to immunize, etc.

Key findings of the study-

  • Disease prevention- Patients with IBD are more likely to develop weak bones, infections like influenza and tuberculosis and certain cancers of the skin, cervix and colon, depending on the type of medications they use.
  • Medication Adherence- Most patients are not taking their IBD medications correctly all of the time. In general, people felt better when they had a high medication adherence score.
  • Quality of life: Patients with severe ulcerative colitis had low quality of life, but quality of life returned to around average when patients had surgery to remove their colon and replace it with an internal pouch
  • Patient reported outcomes - IBD patients had more anxiety, depression, fatigue and sleep disturbance, and less social satisfaction than the general population. Using corticosteroids made all of the outcomes worse.

PIANO study- Registry of Pregnant women with IBD and their offspring to determine if IBD medications affects pregnancy and health of the baby.

  • 1115 women (of which 896 delivered) were followed
  • Patients on different medications (biologics, immunosuppressants) were studied and compared to unmedicated

Key findings-

  • IBD medication exposure during pregnancy was not associated with abnormalities in:
    • Rate of congenital anomalies
    • Infant height and weight
    • Overall rates of infections
    • Developmental milestones at months 4,9,12
  • Of the patients studied, those on biologics alone had a slightly increased rate of
    • Spontaneous abortions
    • C-sections

**These results may relate to the fact that patients with more severe disease took biologic therapies

  • Of the patients studied, those on combination therapy (Biologics and immunosuppressants) had a slightly increased rate of-
    • Preterm birth
    • Infections at 12 months
      • UC: Any complication, premature delivery, low birth weight, neonatal intensive care unit

      **Again, these results may be due to the aggressive disease that led to combination drug use rather than the agents themselves

Last Updated: August 2012