Registries & Real-World Data in IBD

Registry and real-world data studies follow large groups of people with inflammatory bowel disease (IBD) in routine care, often for many years. These projects complement clinical trials by capturing how treatments perform outside strict research settings, and by tracking uncommon or delayed side effects. For families, clinicians, and regulators, registry findings are a key source of evidence on long-term safety, pregnancy outcomes, cancer risk, and life-course outcomes in IBD.

Key Takeaways

• Registries and real-world data follow people with IBD in everyday care to study long-term safety and outcomes.

• These data help reveal rare or delayed risks, such as certain infections or cancers, that short clinical trials cannot fully capture.

• Large IBD registries like TREAT, ENEIDA, I-CARE, and PIANO have shaped understanding of biologic safety, thiopurine cancer risk, and pregnancy outcomes.

• Real-world data show that disease activity and steroid use often drive complications more than many modern biologic drugs.

• Health agencies such as the FDA and EMA now formally use real-world evidence to support labeling changes and post-approval safety decisions.

• Registries cannot fully prove cause and effect, but they are essential partners to randomized trials when weighing long-term benefits and risks.

What Are Registries and Real-World Data?

Real-world data (RWD) are health information collected during routine care, not in tightly controlled trials. Examples include electronic health records, insurance claims, disease or drug registries, and even data from digital health tools.(fda.gov)

Real-world evidence (RWE) is the clinical evidence that comes from analyzing this kind of data. It helps describe how treatments work, and what risks appear, in everyday practice rather than in ideal trial conditions.(fda.gov)

An IBD registry is a structured database that systematically follows people with Crohn’s disease or ulcerative colitis over time. Teams record diagnoses, treatments, disease activity, complications, surgeries, and often patient-reported outcomes. Examples include national registries, pregnancy registries, or biologic safety cohorts.

Why Registries Matter in IBD

Randomized controlled trials are the gold standard for testing whether a drug works. But they usually:

• Enroll selected patients without many other illnesses

• Run for months to a few years, not decades

• Focus on symptom scores and short-term side effects

Registries and other real-world datasets fill important gaps:

• Long-term safety across 5, 10, or more years

• Rare events, such as unusual infections or cancers, that need very large numbers of patients to detect

• Under-represented groups, such as older adults, people with many other conditions, or those on multiple medicines

• Patterns of care, including which drugs are started first, how often people switch, and how often remission leads to fewer surgeries or hospitalizations(pubmed.ncbi.nlm.nih.gov)

Together, trials and registries give a fuller picture of what therapies really mean over a lifetime with IBD.

Major IBD Registries and What They Have Shown

Biologic Safety and Disease Outcomes

• TREAT registry (United States)
  The TREAT registry followed more than 6,000 people with Crohn’s disease treated with infliximab or other therapies. Over more than 5 years of follow-up, overall mortality and malignancy rates were similar between infliximab-treated and non-biologic groups. After adjusting for disease severity and other drugs, serious infection risk was linked more to prednisone, narcotic pain medicines, and more severe disease than to infliximab itself.(pubmed.ncbi.nlm.nih.gov)

• I-CARE (Europe)
  I-CARE is a large European prospective registry designed to track long-term safety of immunomodulators and biologics, including anti-TNF agents and vedolizumab. It collects monthly data on infections, cancers, hospitalizations, and procedures in over 10,000 people with IBD.(academic.oup.com)

• ENEIDA (Spain)
  ENEIDA is a nationwide Spanish IBD registry that has become a major platform for studying treatment patterns, genetic and environmental factors, and safety issues such as tuberculosis screening before biologics.(pubmed.ncbi.nlm.nih.gov)

• Danish nationwide cohorts
  Linked health registers in Denmark allow researchers to track biologic use, treatment persistence, surgeries, and costs in all people with IBD starting biologics. Studies show rising biologic use over time and provide real-world estimates of how often patients stay on therapy or need surgery.(pubmed.ncbi.nlm.nih.gov)

These large datasets help clarify whether signals seen in trials hold up in routine practice and across different health systems.

Pregnancy and Medication Safety

PIANO (United States) is a long-running pregnancy registry that follows women with IBD and their children. As of recent reports, more than 2,000 pregnancies have been enrolled. Analyses have found:

• No increase in major birth defects, miscarriages, preterm birth, low birth weight, or early-life infections in infants exposed in utero to biologics or thiopurines, compared with unexposed infants.(pianostudy.org)

• Higher rates of preterm birth and low birth weight in women who required systemic steroids, suggesting that active disease and steroid use, not biologics, are key drivers of poor outcomes.(pianostudy.org)

These findings directly inform counseling about continuing biologics or thiopurines during pregnancy and breastfeeding.

Cancer and Infection Risks With Older Immunosuppressants

Several large registries and population-based cohorts, including the French CESAME study, have examined long-term risks of thiopurines (azathioprine and 6-mercaptopurine):

• A higher rate of lymphoproliferative disorders (lymphomas) in people currently or previously exposed to thiopurines, compared with those never exposed.(pubmed.ncbi.nlm.nih.gov)

• An increased risk of non-melanoma skin cancer, especially with persistent thiopurine use and in fair-skinned individuals.(pubmed.ncbi.nlm.nih.gov)

Meta-analyses suggest that the absolute risk for an individual remains low, but the signal is consistent enough that many guidelines recommend sun protection and regular skin checks for long-term thiopurine users.(pubmed.ncbi.nlm.nih.gov)

These are the kinds of long-latency risks that would be almost impossible to quantify from short clinical trials alone.

How Real-World Data Shape Care and Policy

Findings from IBD registries and other real-world sources influence practice in several ways:

• Treatment counseling
  Conversations about thiopurines now routinely include discussion of small but measurable lymphoma and skin cancer risks. At the same time, clinicians can explain that long-term registry data for many biologics have not shown large increases in overall cancer or mortality compared with conventional therapy.(pubmed.ncbi.nlm.nih.gov)

• Pregnancy planning
  PIANO data support the message that continuing most biologics and thiopurines during pregnancy is usually safer than allowing uncontrolled disease, while highlighting the risks of high-dose steroids and active inflammation.(pianostudy.org)

• Screening and monitoring
  Registry analyses have helped refine recommendations for tuberculosis screening before biologics, skin cancer checks during thiopurine therapy, and colon cancer surveillance strategies.(mdpi.com)

• Health system and regulatory decisions
  Agencies such as the FDA and EMA now have formal frameworks for using registry and other real-world data to support label updates, new indications, or post-approval safety requirements.(fda.gov)

• Understanding medication use patterns
  Claims and registry studies show that many adults with IBD struggle with adherence to biologics and may switch or discontinue earlier than in trials. This has encouraged development of support programs and consideration of simpler dosing schedules.(pubmed.ncbi.nlm.nih.gov)

Strengths and Limits of Registries and Real-World Data

Key strengths

• Very large sample sizes and long follow-up

• Inclusion of people often excluded from trials, such as older adults and those with multiple conditions

• Ability to study many treatments and combinations at once

• Rich information on hospitalizations, surgeries, and costs

Key limits

• No random assignment, so confounding factors can blur cause and effect

• Incomplete or inconsistent data entry, especially for lifestyle factors or over-the-counter medicines

• Delays between real-time care and data availability

• Variable data quality across centers and countries

For these reasons, registry findings are most powerful when combined with trial results, biological plausibility, and expert review.

Where Patient-Generated Data Fit In

Regulators now recognize digital health tools and patient-generated data as part of real-world data.(fda.gov) Symptom trackers, home stool tests, and apps that record diet, sleep, and stress may eventually link with registries to provide an even more complete picture of life with IBD.

Such integration could help researchers understand not only whether a drug prevents surgery, but also how it affects day-to-day pain, fatigue, function at work or school, and mental health over many years.

FAQs

How is a registry different from a clinical trial?

A registry observes what happens in routine care without assigning treatments, while a clinical trial randomly assigns treatments under strict rules. Trials are best for proving that a drug works; registries are best for understanding long-term safety and real-life use.

Are registry results as “trustworthy” as trial results?

Registry studies are very useful for safety and rare events, but they are more vulnerable to bias because treatments are not randomized. Strong registry work uses careful statistics and is interpreted alongside trial data and other research.

Do registry findings apply to every person with IBD?

Registries usually include a wide range of people, which helps generalization. Still, results describe averages across many individuals. Care teams use registry evidence as a guide, then apply it to each person’s specific situation and preferences.