Precision Medicine in Multimorbidity

Abstract

Multimorbidity -- the coexistence of two or more chronic conditions in the same patient -- has become the dominant clinical reality in European healthcare systems, affecting over 60% of adults above age 65 and contributing disproportionately to healthcare costs, mortality, and quality of life impact. Precision medicine approaches developed for single-disease contexts have limited applicability to multimorbid patients, whose care involves complex interactions between multiple disease processes, polypharmacy, functional limitations, and social circumstances that single-disease guidelines and precision therapy paradigms do not address. The gap between precision medicine promise and multimorbidity reality has become a priority focus for European health research and care delivery policy. We evaluated five precision medicine frameworks for multimorbidity applied to 98,624 multimorbid patients across 22 European clinical networks in Vienna, Stockholm, Madrid, Utrecht, and Manchester between 2018 and 2024. Frameworks ranged from single-disease guideline stacking through integrated cluster-informed precision management with shared decision-making for goal prioritisation. Performance was benchmarked using our Multimorbidity Precision Effectiveness Score (MPES), integrating treatment goal alignment, medication burden, functional outcome, patient-reported outcomes, and implementation feasibility. The cluster-informed integrated framework achieved the highest MPES (0.912), reducing medication count from median 11.2 to 7.8 medications per patient, improving functional outcomes by 18.4%, and achieving 84.2% patient goal alignment versus 42.6% under single-disease guideline stacking. Cardiometabolic-musculoskeletal multimorbidity clusters showed the largest benefits from integrated approaches.