Machine Learning Algorithms for Objective Remission and Clinical Outcomes with Thiopurines.
OBJECTIVE
Big data analytics leverage patterns in data to harvest valuable information, but are rarely implemented in clinical care. Optimising thiopurine therapy for inflammatory bowel disease [IBD] has proved difficult. Current methods using 6-thioguanine nucleotide [6-TGN] metabolites have failed in randomized controlled trials [RCTs], and have not been used to predict objective remission [OR]. Our aims were to: 1) develop machine learning algorithms [MLA] using laboratory values and age to identify patients in objective remission on thiopurines; and 2) determine whether achieving algorithm-predicted objective remission resulted in fewer clinical events per year.


METHODS
Objective remission was defined as the absence of objective evidence of intestinal inflammation. MLAs were developed to predict three outcomes: objective remission, non-adherence, and preferential shunting to 6-methylmercaptopurine [6-MMP]. The performance of the algorithms was evaluated using the area under the receiver operating characteristic curve [AuROC]. Clinical event rates of new steroid prescriptions, hospitalisations, and abdominal surgeries were measured.


RESULTS
Retrospective review was performed on medical records of 1080 IBD patients on thiopurines. The AuROC for algorithm-predicted remission in the validation set was 0.79 vs 0.49 for 6-TGN. The mean number of clinical events per year in patients with sustained algorithm-predicted remission [APR] was 1.08 vs 3.95 in those that did not have sustained APR [p < 1 x 10-5]. Reductions in the individual endpoints of steroid prescriptions/year [-1.63, p < 1 x 10-5], hospitalisations/year [-1.05, p < 1 x 10-5], and surgeries/year [-0.19, p = 0.065] were seen with algorithm-predicted remission.


CONCLUSIONS
A machine learning algorithm was able to identify IBD patients on thiopurines with algorithm-predicted objective remission, a state associated with significant clinical benefits, including decreased steroid prescriptions, hospitalisations, and surgeries.
Department of Veterans Affairs Center for Clinical Management Research, Ann Arbor, MI, USA.|Division of Gastroenterology, University of Michigan, Ann Arbor, MI, USA.
Akbar K
AK
Waljee
Division of Gastroenterology, University of Michigan, Ann Arbor, MI, USA.
Kay
K
Sauder
Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Anand
A
Patel
Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Sandeep
S
Segar
Department of Statistics, University of Michigan, Ann Arbor, MI, USA.
Boang
B
Liu
Department of Statistics, University of Michigan, Ann Arbor, MI, USA.
Yiwei
Y
Zhang
Department of Statistics, University of Michigan, Ann Arbor, MI, USA.
Ji
J
Zhu
Division of Gastroenterology, University of Michigan, Ann Arbor, MI, USA.
Ryan W
RW
Stidham
Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
Ulysses
U
Balis
Division of Gastroenterology, University of Michigan, Ann Arbor, MI, USA.
Peter D R
PDR
Higgins
D000293:Adolescent; D000328:Adult; D000465:Algorithms; D019540:Area Under Curve; D001379:Azathioprine / Q000378:metabolism / Q000627:therapeutic use*; D011307:Drug Prescriptions; D005260:Female; D006760:Hospitalization; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000601:surgery; D000069550:Machine Learning; D008297:Male; D055118:Medication Adherence; D015122:Mercaptopurine / Q000031:analogs & derivatives / Q000378:metabolism / Q000627:therapeutic use*; D008875:Middle Aged; D012372:ROC Curve; D012074:Remission Induction; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult
D007166:Immunosuppressive Agents; C010240:6-methylthiopurine; D015122:Mercaptopurine; D001379:Azathioprine
Inflammatory bowel disease; immunosuppression; inflammation; thiopurines