Automatic identification of methotrexate-induced liver toxicity in patients with rheumatoid arthritis from the electronic medical record

J Am Med Inform Assoc. 2015 Apr;22(e1):e151-61. doi: 10.1136/amiajnl-2014-002642. Epub 2014 Oct 25.


Objectives: To improve the accuracy of mining structured and unstructured components of the electronic medical record (EMR) by adding temporal features to automatically identify patients with rheumatoid arthritis (RA) with methotrexate-induced liver transaminase abnormalities.

Materials and methods: Codified information and a string-matching algorithm were applied to a RA cohort of 5903 patients from Partners HealthCare to select 1130 patients with potential liver toxicity. Supervised machine learning was applied as our key method. For features, Apache clinical Text Analysis and Knowledge Extraction System (cTAKES) was used to extract standard vocabulary from relevant sections of the unstructured clinical narrative. Temporal features were further extracted to assess the temporal relevance of event mentions with regard to the date of transaminase abnormality. All features were encapsulated in a 3-month-long episode for classification. Results were summarized at patient level in a training set (N=480 patients) and evaluated against a test set (N=120 patients).

Results: The system achieved positive predictive value (PPV) 0.756, sensitivity 0.919, F1 score 0.829 on the test set, which was significantly better than the best baseline system (PPV 0.590, sensitivity 0.703, F1 score 0.642). Our innovations, which included framing the phenotype problem as an episode-level classification task, and adding temporal information, all proved highly effective.

Conclusions: Automated methotrexate-induced liver toxicity phenotype discovery for patients with RA based on structured and unstructured information in the EMR shows accurate results. Our work demonstrates that adding temporal features significantly improved classification results.

Keywords: electronic medical record; liver toxicity; methotrexate; natural language processing; pharmacogenetic; rheumatoid arthritis.

Publication types

  • Research Support, N.I.H., Extramural
  • Validation Study

MeSH terms

  • Algorithms*
  • Arthritis, Rheumatoid / drug therapy*
  • Chemical and Drug Induced Liver Injury / diagnosis*
  • Electronic Health Records*
  • Humans
  • Immunosuppressive Agents / adverse effects*
  • Liver / drug effects
  • Methotrexate / adverse effects*


  • Immunosuppressive Agents
  • Methotrexate