Individualized Management of Osteoarthritis: The Role of Pharmacogenomics to Optimize Pain Therapy

Osteoarthritis (OA) is a multifactorial, degenerative joint disease that significantly impairs mobility and quality of life, especially among older adults. The growing aging population and increasing obesity rates are expected to increase the incidence and prevalence of OA. In the absence of Disease Modifying Antirheumatic Drugs (DMARs) for OA, current treatment strategies largely focus on symptom relief rather than disease modification and often fail to account for the substantial inter-individual variability in drug response. Pharmacogenomics (PGx), the study of how genetic variation influences drug response, offers a promising approach to personalize OA therapy. This review explores the clinical and pharmacogenomic considerations of commonly used OA medications - acetaminophen, NSAIDs, duloxetine, and tramadol - focusing on gene-drug interactions that influence efficacy, safety, and metabolism. Evidence-based recommendations from the Clinical Pharmacogenetics Implementation Consortium guidelines are discussed where applicable to highlight actionable genetic variants such as CYP2D6, CYP2C9, CYP2E1, and UGT1A6. While PGx data is not currently embedded in OA clinical treatment guidelines, its integration into clinical practice may enhance therapeutic outcomes and minimize adverse effects. This review underscores the potential of PGx as a clinical tool in OA pain management, paving the way toward truly personalized medicine.