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Longitudinal trajectories of fatigue in early RA: the role of inflammation, perceived disease impact and early treatment response
  1. Michaël Doumen1,2,
  2. Sofia Pazmino1,
  3. Delphine Bertrand1,
  4. Diederik De Cock1,3,
  5. Johan Joly2,
  6. René Westhovens1,2,
  7. Patrick Verschueren1,2
  1. 1 Department of Development and Regeneration, KU Leuven, Leuven, Belgium
  2. 2 Rheumatology, KU Leuven University Hospitals Leuven, Leuven, Belgium
  3. 3 Department of Public Health, Biostatistics and Medical Informatics Research Group, Vrije Universiteit Brussel, Brussels, Belgium
  1. Correspondence to Dr Michaël Doumen, Department of Development and Regeneration, KU Leuven, Leuven, Flanders, Belgium; michael.doumen{at}


Objective Fatigue is common in rheumatoid arthritis (RA). We aimed to explore its longitudinal course, predictors and association with disease activity in early RA.

Methods Data came from the 2-year treat-to-target trial CareRA (Care in early RA) and its 3-year extension. Fatigue was measured on Visual Analogue Scale, Multidimensional Fatigue Inventory and Short Form-36 (SF-36) vitality. Longitudinal fatigue trajectories were identified with multivariate growth mixture modelling. Early predictors of fatigue and the association of fatigue and its trajectories with disease activity and clinical/psychosocial outcomes were studied with linear mixed models and multilevel mediation.

Results We included 356 and 244 patients in the 2-year and 5-year analyses, respectively. Four fatigue trajectories were identified: rapid, gradual, transient improvement and early deterioration, including 10%, 14%, 56% and 20% of patients. Worse pain, mental health and emotional functioning were seen in the early deterioration group. Higher pain, patient global assessment (PGA) and disability (Health Assessment Questionnaire), lower SF-36 mental components, and fewer swollen joints at baseline predicted higher fatigue over 5 years, while early disease remission strongly improved 5-year fatigue. The association between Simple Disease Activity Index and fatigue was mediated by PGA, pain, mental health and sleep quality.

Conclusions Although fatigue evolves dynamically over time in early RA, most patients do not achieve sustained fatigue improvement despite intensive disease-modifying antirheumatic drug therapy. Higher 5-year fatigue levels were seen in patients with more perceived disease impact and fewer swollen joints at baseline. Conversely, early inflammatory disease control strongly improved long-term fatigue, pointing towards an early window of opportunity to prevent persistent fatigue.

  • rheumatoid arthritis
  • patient reported outcome measures
  • epidemiology

Data availability statement

Data are available upon reasonable request. The data sets used and/or analysed during the current study are available from the corresponding author on reasonable request.

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Data availability statement

Data are available upon reasonable request. The data sets used and/or analysed during the current study are available from the corresponding author on reasonable request.

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  • Handling editor Josef S Smolen

  • Twitter @DoumenMichael, @sophie_33pl, @DiederikDeCock

  • Contributors PV, JJ and RW designed the study protocol in collaboration with the CareRA study group. Investigators of the CareRA study group, including PV and RW, recruited and enrolled patients and were responsible for daily patient management. PV and JJ were responsible for coordination of the trial and collection of data. MD analysed the data and drafted the article. All authors contributed to interpretation of the data and revised the article critically for content. All authors gave final approval of the manuscript to be published. PV and MD are the guarantors.

  • Funding MD has received a Strategic Basic Research Fellowship grant from Fonds Wetenschappelijk Onderzoek (FWO) (grant number 1S85521N). CareRA was supported by a grant from the Flemish Government Agency for Innovation by Science and Technology (IWT) and by grants from the Fund for Scientific Research in Rheumatology (FWRO) and the Academic Foundation of Leuven. The interpretations and conclusions presented in this publication are independent and were in no way influenced by the funding source.

  • Competing interests None declared.

  • Patient and public involvement Patients and/or the public were involved in the design, or conduct, or reporting, or dissemination plans of this research. Refer to the Methods section for further details.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.