A Machine Learning-Based Test for Predicting Response to Psoriasis Biologics

Jerry Bagel, Yipeng Wang, Paul Montgomery, Christian Abaya, Eric Andrade, Courtney Boyce, Tatiana Tomich, Byung In Lee, David Pariser, Alan Menter, Tobin J. Dickerson

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Objective: This study was designed to develop and prospectively validate a machine learning based algorithm that could predict patient response to the most common biologic drug classes used in the management of psoriasis patients. This type of tool would allow clinicians to have greater confidence that a given patient will respond to a specific drug class, which could lead to improved health outcomes and reduced wasted healthcare spend. Methods: Patients were enrolled into one of two observational studies (STAMP studies) where dermal biomarker patches (DBPs) were applied at baseline prior to drug exposure, followed by clinical evaluations at 12 weeks after exposure. PASI measurements were made at baseline and 12 weeks to evaluate clinical response to a clinical phenotype. Responders were defined as those who reached PASI75 at 12 weeks. The transcriptomes obtained from the DBPs were sequenced and analyzed to derive and/or validate classifiers for each biologic class, which were then combined to yield predictive responses for all three biologic drug classes (IL-23i, IL-17i, and TNFαi). Results: A total of 242 psoriasis patients were enrolled in these studies, including 118 patients (49.6%) treated with IL-23i, 79 patients (33.2%) treated with IL-17i, 35 patients (14.7%) treated with TNFαi, and 6 patients (2.5%) treated with IL-12/23i. The IL-23i predictive classifier was developed from the earlier enrolled patients and independently validated with the latter enrolled patients. IL-17i and TNFαi predictive classifiers were developed using publicly available datasets and independently validated with patients from the STAMP studies. In the independent validation, positive predictive values for three classifiers (IL-23i, IL-17i, and TNFαi) were 93.1%, 92.3% and 85.7% respectively. Over the entire cohort, 99.5% of patients were predicted to respond to at least one drug class. Conclusion: This study demonstrates the power of using baseline dermal biomarkers and machine learning methods as applied to the prediction of patient response to psoriasis biologics prior to drug exposure. Using this test, patients, physicians, and the health care system all can benefit in distinct ways. Precision medicine can be realized for individual patients as most will likely respond to their prescribed biologic the first time. Physicians can prescribe these drugs with increased confidence, and the healthcare system will realize lower net costs as well as greatly reduced wasted spend by significantly improving initial response rates to expensive biologic therapeutics.

Original languageEnglish
Pages (from-to)621-638
Number of pages18
JournalSKIN: Journal of Cutaneous Medicine
Volume5
Issue number6
DOIs
StatePublished - 2021
Externally publishedYes

Keywords

  • biologics
  • machine learning
  • precision medicine
  • psoriasis

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