Development and validation of multivariable prediction models for adverse COVID-19 outcomes in IBD patients

Importance: Risk calculators can facilitate shared medical decision-making 1 . Demographics, comorbidities, medication use, geographic region, and other factors may increase the risk for COVID-19-related complications among patients with IBD 2,3 . Objectives: Develop an individualized prognostic risk prediction tool for predicting the probability of adverse COVID-19 outcomes in patients with IBD. Design Setting and Participants: This study developed and validated prognostic penalized logistic regression models 4 using reports to Surveillance Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD) from March-October 2020. Model development was done using a training data set (85% of cases reported March 13 - September 15, 2020), and model validation was conducted using a test data set (the remaining 15% of cases plus all cases reported September 16-October 20, 2020). Main Outcomes and Measures: COVID-19 related:Hospitalization+: composite outcome of hospitalization, ICU admission, mechanical ventilation, or deathICU+: composite outcome of ICU admission, mechanical ventilation, or deathDeathWe assessed the resulting models' discrimination using the area under the curve (AUC) of the receiver-operator characteristic (ROC) curves and reported the corresponding 95% confidence intervals (CIs). Results: We included 2709 cases from 59 countries (mean age 41.2 years [s.d. 18], 50.2% male). A total of 633 (24%) were hospitalized, 137 (5%) were admitted to the ICU or intubated, and 69 (3%) died. 2009 patients comprised the training set and 700 the test set. The models demonstrated excellent discrimination, with a test set AUC (95% CI) of 0.79 (0.75, 0.83) for Hospitalization+, 0.88 (0.82, 0.95) for ICU+, and 0.94 (0.89, 0.99) for Death. Age, comorbidities, corticosteroid use, and male gender were associated with higher risk of death, while use of biologic therapies was associated with a lower risk. Conclusions and Relevance: Prognostic models can effectively predict who is at higher risk for COVID-19-related adverse outcomes in a population of IBD patients. A free online risk calculator ( https://covidibd.org/covid-19-risk-calculator/ ) is available for healthcare providers to facilitate discussion of risks due to COVID-19 with IBD patients. The tool numerically and visually summarizes the patient's probabilities of adverse outcomes and associated CIs. Helping physicians identify their highest-risk patients will be important in the coming months as cases rise in the US and worldwide. This tool can also serve as a model for risk stratification in other chronic diseases. Key Points: Question: How well can a multivariable risk model predict the risk of hospitalization, intensive care unit (ICU) stay, or death due to COVID-19 in patients with inflammatory bowel disease (IBD)?Findings: Multivariable prediction models developed using data from an international voluntary registry of IBD patients and available for use online ( https://covidibd.org/ ) have very good discrimination for predicting hospitalization (Test set AUC 0.79) and excellent discrimination for ICU admission (Test set AUC 0.88) and death (Test set AUC 0.94). The models were developed with a training sample of 2009 cases and validated in an independent test sample of 700 cases comprised of a random sub-sample of cases and all cases entered in the registry during a one-month period after model development. Meaning: This risk prediction model may serve as an effective tool for healthcare providers to facilitate conversations about COVID-19-related risks with IBD patients.