Machine Learning Algorithms for Objective Remission and Clinical Outcomes with Thiopurines

J Crohns Colitis. 2017 Jul 1;11(7):801-810. doi: 10.1093/ecco-jcc/jjx014.


Background and aims: 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.

Keywords: Inflammatory bowel disease; immunosuppression; inflammation; thiopurines.

MeSH terms

  • Adolescent
  • Adult
  • Algorithms*
  • Area Under Curve
  • Azathioprine / metabolism
  • Azathioprine / therapeutic use*
  • Drug Prescriptions
  • Female
  • Hospitalization
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Inflammatory Bowel Diseases / drug therapy*
  • Inflammatory Bowel Diseases / surgery
  • Machine Learning*
  • Male
  • Medication Adherence
  • Mercaptopurine / analogs & derivatives
  • Mercaptopurine / metabolism
  • Mercaptopurine / therapeutic use*
  • Middle Aged
  • ROC Curve
  • Remission Induction*
  • Retrospective Studies
  • Treatment Outcome
  • Young Adult


  • Immunosuppressive Agents
  • 6-methylthiopurine
  • Mercaptopurine
  • Azathioprine