Published online Aug 14, 2019. doi: 10.3748/wjg.v25.i30.4235
Peer-review started: January 22, 2019
First decision: February 13, 2019
Revised: July 3, 2019
Accepted: July 5, 2019
Article in press: July 5, 2019
Published online: August 14, 2019
A great deal has been written on the treatment of moderate to severe Crohn’s disease. There is a subset of patients with milder disease, who may be able to avoid potent long-term immune suppression. However, there is little or no data on the natural history of patients who are not treated with immune suppressive agents. This is particularly relevant in children, who if treated with immune suppression agents, may be at risk for serious toxicities such as infection and lymphoma. However, the under treatment of Crohn’s disease could increase the risk of the development of complications. We therefore desired to study the natural history of patients who were not treated with immune suppressive agents.
Children with mild or limited Crohn’s disease are a poorly studied population. Phenotypic features, natural history, treatments used, and long-term outcomes of children with mild disease is unclear. We wanted to assess whether there are phenotypic differences such as disease location or disease behavior in mild vs moderate and/or severe Crohn’s disease at the time of diagnosis. We also wanted to define long-term outcome in the mild population. We wanted to see whether these patients develop complications or require surgery over time, and if so, what is the time to escalation in therapy and also, what are the predictors of escalation.
The objective of the study was to determine the prevalence of complications in patients who did not receive immunomodulators or biologics for at least 2 years after initial diagnosis. We identified a small subset of patients in our cohort who were treated this way. We then reviewed charts in order to determine the event-free survival, i.e., the time until treatment was escalated to immunomodulators, biologics, or surgery.
We conducted a retrospective chart review of the Inflammatory Bowel Disease Database at Boston Children’s Hospital. We went through the detailed clinic visits, laboratory studies and procedures for all the patients that met our inclusion criteria. And data was then filed into a Redcap database. Descriptive statistics were used to summarize subject characteristics at disease diagnosis. Chi-squared tests were utilized to assess categorical variables and independent T-tests were used to compare continuous variables. Z scores were used to describe height data.
We identified a subset of patients who were able to avoid immune suppression for prolonged periods of time, up to a decade. Interestingly, only a subset of these patients (approximately 30%) required escalation to more potent immunosuppression on clinical grounds. Patients that required steroid courses after the first 2 years and had more complications were more likely to require escalation in therapy. However, treatment without immunosuppressive drugs (such as aminosalicylates), while often resulting in clinical improvement, did not result in histologic healing in the vast majority of patients.
Not every child with new onset Crohn’s disease requires the early institution of immunosuppressive agents (such as methotrexate, mercaptopurine, or anti-TNF treatment) immediately after diagnosis. There is a small subset of children with mild Crohn’s disease, who can be maintained on aminosalicylate therapy alone, and not require drug escalation for several years. Currently, the phenotype that may have the best response to aminosalicylate therapy is mild colonic disease.
Mild Crohn’s patients may be able to be identified in the future through genetic or serologic predictive models. It’s important to stratify low risk patients and prevent overtreatment with immunomodulators and biologics. Future research should focus on establishing more genotypic and environmental data to better characterize this low risk population.