Monitoring for 5-aminosalicylate toxicity: prognostic model development and validation.

Background and aim: To develop and validate a prognostic model for risk-stratified monitoring of 5-aminosalicylate (5-ASA) toxicity. Methods: This nationwide retrospective cohort study used data from the Clinical Practice Research Datalink (CPRD) Aurum and Gold for model development and validation respectively. It included adults newly diagnosed with inflammatory bowel disease (IBD) and established on 5-ASAs between 01/01/2007 and 31/12/2019. 5-ASA discontinuation with abnormal monitoring blood test result was the outcome of interest. Patients prescribed 5-ASAs for ≥6 months i.e., established on treatment, were followed-up for up to five years. Penalised Cox-regression was used to develop the risk equation. Model performance was assessed in terms of calibration and discrimination. Statistical analysis was performed using STATA (StataCorp LLC). Results: 14,109 and 7,523 participants formed the development and validation cohorts with 401 and 243 events respectively. 185, 172, and 64 discontinuations were due to cytopenia, elevated creatinine and elevated liver enzymes respectively in the derivation cohort. Hazardous alcohol intake, chronic kidney disease, thiopurine use, and blood test abnormalities before follow-up were strong prognostic factors. The optimism adjusted R2D in development data was 0.08. The calibration slope and Royston D statistic (95% Confidence Interval) in validation cohort were 0.90 (0.61-1.19) and 0.57 (0.37-0.77) respectively. Conclusion: This prognostic model utilises information available during routine clinical care and can be used to inform decisions on the interval between monitoring blood-tests. The results of this study ought to be considered by guideline writing groups to risk-stratify blood test monitoring during established 5-ASA treatment.