Development and Validation of Machine Learning Models in Prediction of Remission in Patients With Moderate to Severe Crohn Disease

IMPORTANCE Biological therapies have revolutionized inflammatory bowel disease management, but many patients do not respond to biological monotherapy. Identification of likely responders could reduce costs and delays in remission. OBJECTIVE To identify patients with Crohn disease likely to be durable responders to ustekinumab before committing to long-term treatment. DESIGN, SETTING, AND PARTICIPANTS This cohort study analyzed data from 3 phase 3 randomized clinical trials (UNITI-1, UNITI-2, and IM-UNITI) conducted from 2011 to 2015. Participants (n = 401) were individuals with active (C-reactive protein [CRP] measurement of =5 mg/L at enrollment) Crohn disease who received ustekinumab therapy. Data analysis was performed from November 1, 2017, to June 1, 2018. EXPOSURES All included patients were exposed to 1 or more dose of ustekinumab for 8 weeks or more. MAIN OUTCOMES AND MEASURES Random forest methods were used in building 2 models for predicting Crohn disease remission, with a CRP level lower than 5 mg/dL as a proxy for biological remission, beyond week 42 of ustekinumab treatment. The first model used only baseline data, and the second used data through week 8. RESULTS In total, 401 participants, with a mean (SD) age of 36.3 (12.6) years and 170 male (42.4%), were included. The week-8 model had a mean area under the receiver operating characteristic curve (AUROC) of 0.78 (95% CI, 0.69-0.87). In the testing data set, 27 of 55 participants (49.1%) classified as likely to have treatment success achieved success with a CRP level lower than 5 mg/L after week 42, and 7 of 65 participants (10.8%) classified as likely to have treatment failure achieved this outcome. In the full cohort, 87 patients (21.7%) attained remission after week 42. A prediction model using the week-6 albumin to CRP ratio had an AUROC of 0.76 (95% CI, 0.71-0.82). Baseline ustekinumab serum levels did not improve the model's prediction performance. CONCLUSIONS AND RELEVANCE In patients with active Crohn disease, demographic and laboratory data before week 8 of treatment appeared to allow the prompt identification of likely nonresponders to ustekinumab without the need for costly drug-level monitoring.