Identification and Validation of Clinically Relevant Clusters of Severe Fatigue in Rheumatoid Arthritis

Neil Basu, Gareth T Jones, Gary J MacFarlane, Katie L Druce

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10 Citations (Scopus)
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Objectives: The considerable heterogeneity of rheumatoid arthritis (RA) related fatigue is the greatest challenge to determining pathogenesis. The identification of homogenous sub-types of severe fatigue would inform the design and analysis of experiments seeking to characterise the likely numerous causal pathways which underpin the symptom. This study aimed to identify and validate such fatigue sub-types in patients with RA.
Methods: Data were obtained from patients recruited to the British Society for Rheumatology Biologics register for RA, as either receiving traditional Disease Modifying Anti-Rheumatic Drugs (DMARD cohort, n=522) or commencing anti-TNF therapy (anti-TNF cohort, n=3909). In those reporting severe fatigue (SF36 vitality≤12.5), this cross-sectional analysis applied hierarchical clustering with weighted-average linkage identified clusters of pain, fatigue, mental health (all SF36), disability (HAQ) and inflammation (ESR) in the DMARD cohort. K-means clustering sought to validate the solution in the anti-TNF cohort. Clusters were characterised using a priori generated symptom definitions and between-cluster comparisons.
Results: Four severe fatigue clusters, labelled as basic (46%), affective (40%), inflammatory (4.5%) and global (8.9%) were identified in the DMARD cohort. All clusters had severe levels of pain and disability, and were distinguished by the presence/absence of poor mental health and high inflammation. The same symptom clusters were present in the anti-TNF cohort, though the proportion of participants in each cluster differed (basic:28.7%, affective:30.2%, global:24.1%, inflammatory:16.9%).
Conclusions: Among RA patients with severe fatigue, recruited to two diverse RA cohorts, clinically relevant clusters were identified and validated. These may provide the basis for future mechanistic studies and ultimately support a stratified approach to fatigue management.
Original languageEnglish
Pages (from-to)1051-1058
Number of pages8
JournalPsychosomatic Medicine
Issue number9
Early online date31 May 2017
Publication statusPublished - Nov 2017

Bibliographical note

The authors have no conflicts of interest to disclose. This work was supported by the Institute of Applied Health Sciences, University of Aberdeen, who provided KD’s PhD studentship.
The BSR commissioned the BSRBR-RA as a UK-wide national project to investigate the safety of biologic agents in routine medical practice. BSR receives restricted income from UK pharmaceutical companies, presently Abbott Laboratories, Merck, Pfizer, Roche, UCB and SOBI. This income finances a wholly separate contract between the BSR and the University of Manchester who provide and oversee the BSRBR-RA data collection, management and analysis service. The principal investigators and their team have full academic freedom and are able to work independently of pharmaceutical industry influence. All decisions concerning analyses, interpretation and publication are made autonomously of any industrial contribution.


  • fatigue
  • pain
  • disability
  • cluster
  • rheumatoid arthritis


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