Predicting the most effective treatment approach for pediatric ulcerative colitis

Recent results from a multi-center clinical study identified several patient characteristics that can predict how well children with ulcerative colitis (UC) will respond to treatment, pointing toward a more personalized approach to treating the disease. UC, a type of inflammatory bowel disease, is caused by a complex combination of genetic, microbial, and environmental factors that provoke chronic and painful inflammation in the lower gastrointestinal tract, resulting in diarrhea, cramping, and malnutrition. People with UC are typically treated with the non-steroidal anti-inflammatory drug mesalazine or corticosteroids, but many do not improve and eventually need to be treated with more potent drugs that suppress the immune response that causes inflammation (immunosuppressive drugs). Advance knowledge of which children with UC only respond to immunosuppressive treatments could enable them to be effectively treated and undergo remission as quickly as possible. However, predicting treatment responses to UC has been difficult due to the disease’s variability from person to person. Determining the best treatment approach has been especially difficult for children with UC because most of the treatments are based upon results from adult studies.

To streamline treatment approaches for UC, particularly in children, the NIDDK supported the Predicting Response to Standardized Pediatric Colitis Therapy (PROTECT) study, which recruited several hundred boys and girls from 29 centers in the United States and Canada who were recently diagnosed with UC. The participants were initially given mesalazine or corticosteroids. After a year, only 38 percent of the participants were able to achieve corticosteroid-free remission—that is, they needed only mesalazine or no treatment at all. A majority of the participants required more intensive treatments, including immunosuppressive drugs, and several required surgeries to remove the colon. Importantly, several patient characteristics—such as high hemoglobin levels, clinical remission after 4 weeks, and the makeup of the gut microbial community— were associated with achieving corticosteroid-free remission, suggesting these characteristics can predict whether immunosuppressive drugs will be necessary. PROTECT researchers also identified certain genes that were more active in the participants who were responsive to corticosteroids, which opens the possibility of genetic screening to help determine which patients would be most likely to benefit from this treatment. Additionally, the researchers found that mitochondria—the tiny battery-like cellular components that supply energy—were less active in the colons of UC patients, such that boosting energy production in colonic cells might be another effective therapeutic approach.

The results from the PROTECT study suggest that the best treatment approaches for UC are those that are tailored to individuals with the disease based upon their clinical, genetic, and microbial profiles. The study also presents a framework for additional clinical studies that will further move UC therapy toward more personalized, and ultimately more effective, approaches.