Longitudinal stability of data-driven fibromyalgia phenotypes across repeated clinical assessments
Kevin V. Hackshaw, Michelle M. Osuna-Diaz, Katherine R. Sebastian, Lianbo Yu, Zhanna Mikulik, M. Monica Giusti, Luis Rodriguez-SaonaAbstract
Introduction:
Fibromyalgia is a heterogeneous chronic condition characterized by variability in pain, psychological distress, central sensitization, and functional impairment. Cross-sectional studies have identified reproducible symptom phenotypes; however, their longitudinal stability remains incompletely understood. Objectives: This study aimed to evaluate the longitudinal stability of data-driven fibromyalgia phenotypes across repeated clinical assessments in a large, harmonized, multi-institutional cohort.
Methods:
We analyzed longitudinal data from 821 adults with fibromyalgia recruited from 2 academic medical centers. Standardized assessments included the Revised Fibromyalgia Impact Questionnaire, Beck Depression Inventory, Central Sensitization Inventory, McGill Pain Questionnaire, and selected SF-36 functional domains. Unsupervised clustering was performed at baseline to derive symptom phenotypes, which were ordered by overall severity. Using baseline-derived model parameters, phenotype membership was assigned at subsequent visits. Phenotype transitions were examined between visit 1 and visit 2 (n = 191) and across visits 1 to 3 (n = 72) using transition matrices and alluvial visualizations.
Results:
Two clinically interpretable fibromyalgia phenotypes were identified at baseline, representing lower-severity/preserved function and higher-severity/global impairment profiles. Across 6-month follow-up intervals, most participants remained within their baseline phenotype (61.9% from visit 1→2 and 64.8% from visit 2→3). Transitions occurred in a minority of individuals and were primarily between adjacent severity phenotypes. Among participants with 3 or more visits, phenotype membership remained stable across repeated assessments.
Conclusion:
Data-driven fibromyalgia phenotypes demonstrate substantial longitudinal stability, supporting their validity as enduring clinical constructs rather than transient symptom states. These findings support phenotype-based stratification for longitudinal research and precision treatment approaches in fibromyalgia. Longitudinal analysis shows that fibromyalgia symptom phenotypes are largely stable over time, with infrequent transitions occurring mainly between adjacent severity groups.