Full Papers
Impact and applicability of pharmacogenomics in rheumatology: an integrated analysis
P. Reid1, K. Danahey2, M. Lopez Velazquez3, M.J. Ratain4, P.H. O'donnell5
- Committee on Clinical Pharmacology and Pharmacogenomics, University of Chicago, Chicago, and Section of Rheumatology, Department of Medicine, University of Chicago, IL, USA. pankti.reid@uchospitals.edu
- Center for Research Informatics, and Center for Personalized Therapeutics, University of Chicago, IL, USA.
- Section of Rheumatology, Department of Medicine, University of Chicago, IL, USA.
- Committee on Clinical Pharmacology and Pharmacogenomics, Center for Personalized Therapeutics, and Department of Medicine, University of Chicago, IL, USA.
- Committee on Clinical Pharmacology and Pharmacogenomics, Center for Personalized Therapeutics, and Department of Medicine, University of Chicago, IL, USA.
CER13724
2021 Vol.39, N°6
PI 1385, PF 1393
Full Papers
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PMID: 33506753 [PubMed]
Received: 23/06/2020
Accepted : 23/11/2020
In Press: 15/01/2021
Published: 25/11/2021
Abstract
OBJECTIVES:
Rheumatology medications are often associated with adverse drug reactions (ADRs) or inadequate response (IR). Pharmacogenomics may be a solution, but there is limited knowledge of its potential utility within rheumatology.
METHODS:
We analysed medication changes and pharmacogenomically actionable prescriptions for all adult rheumatology outpatient encounters at our medical centre between 10/2012-12/2018. Three sources defined pharmacogenomic actionability: FDA labels, Clinical Pharmacogenetics Implementation Consortium guidelines, and our institutionally-deliverable pharmacogenomic clinical decision support (CDS) summaries. A subset of patients (validation cohort) had previously undergone broad, preemptive pharmacogenomic testing within other clinics but results were unavailable within rheumatology. We assessed the occurrence of specific pharmacogenomic ADRs/IRs in this group.
RESULTS:
From 174,834 prescribing events, 6300/7761 patients (81%) had clinically actionable pharmacogenomic drug prescriptions (i.e. institutional CDS summaries would have been deployable if testing had been done). Using more conservative standards (pharmacogenomically actionable by ≥2 guidance bodies), 4158/7761 (54%) patient prescriptions could have been impacted. The greatest proportions of potentially impacted rheumatologic prescriptions were for tramadol (47%), allopurinol (21%), azathioprine (17%) and celecoxib (8%). Among our validation cohort (94 previously-genotyped patients), 29 (31%) patients had a pharmacogenomic genotype that would have cautioned possible ADRs/IRs for ≥1 medication. Four patients actually suffered ADRs/IRs that would have been predicted by preemptive genotyping.
CONCLUSIONS:
Pharmacogenomic genotyping could inform prescribing for the majority of rheumatology patients and may prevent a subset of ADRs/IRs. These findings justify prospective evaluation of pharmacogenomic testing including assessment of cost-effectiveness in selected rheumatology populations to further understand impact on therapy-related toxicities and treatment outcomes.
