BISCUIT - the Biologic dISContinUatIon sTudy

Project start date and end date: 2021 - 2023

Background:
Biologic drugs are increasingly used to treat pediatric patients with inflammatory bowel disease (IBD). However, despite availability of new medications and monitoring techniques, drug discontinuation remains common, leading to loss of treatment options. The reasons for this are varied, and may include developing anti-drug antibodies, adverse drug reactions, insurance problems, among other reasons. This problem can be serious for some patients, who may run out of treatment options before they reach adulthood. There is little evidence to predict risk of biologic drug discontinuation. We propose to evaluate the predictors of and reasons for biologic drug discontinuation among pediatric patients with Crohn’s disease (CD).

Objective:

• Aim 1. Determine the frequency of biologic drug discontinuation, including associations with patient and practice characteristics, as well as drug dosing and monitoring among children with CD.
• Aim 2. Determine the associations between biologic drug discontinuation and adverse events, evaluation performed prior to drug discontinuation, and barriers to care.
• Aim 3. Determine the association between HLA DQA1*05 and risk of developing anti-drug antibodies and discontinuation of biologic medications among children with CD.

Research Topics & Methods:
This is a retrospective cohort study of pediatric patients with CD in the ImproveCareNow Network who have been on any biologic drug at any time during the study period. We will perform per-patient longitudinal analyses, characterizing the time from diagnosis to starting each biologic drug, duration of use of that drug, and changes in dosing. From the available data, we will attempt to determine if subgroups of patients can be identified who are at greater risk of biologic drug discontinuation. We will supplement registry data with information abstracted from the medical record from patients from a subgroup of sites in the ImproveCareNow Network. We will also evaluate serum from patients who enrolled in the COMBINE trial to determine if HLA DQA1*05 predicts risk of developing anti-drug antibodies.

Implications:
It is important to develop strategies for preventing loss of therapeutic options in order to continue to improve long-term outcomes for young people with IBD. We anticipate that armed with information, we will be enabled to develop:

1. Evidence-based predictors of biologic drug discontinuation;
2. Educational materials aimed at reducing unnecessary drug discontinuation;
3. guidelines for improving evaluation prior to drug discontinuation; and
4. published evidence to inform policy aimed at improving insurance coverage of appropriate dosing and monitoring.

Funder:
The project is funded by the Gary and Rachel Glick Charitable Fund.         

Collaborators:
Sabina Ali, Jess Kaplan, Jon Moses, Brad Pasternak, Chip Samson, David Suskind

Project Manager:
Dianne Singer