Impact and applicability of pharmacogenomics in rheumatology: an integrated analysis.

Abstract

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. 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. 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. 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.