Clinical Rheumatology

, Volume 31, Issue 4, pp 717–722 | Cite as

The impact of disease activity, pain, disability and treatments on fatigue in established rheumatoid arthritis

  • Richard Charles John CampbellEmail author
  • Michael Batley
  • Anthony Hammond
  • Fowzia Ibrahim
  • Gabrielle Kingsley
  • David L. Scott
Brief Report


We investigate a range of clinical factors and anti-rheumatic treatments, for their degree of association with rheumatoid arthritis (RA) fatigue in 557 patients. A range of clinical measures concerning disability, pain and disease activity together with drug history were recorded as part of routine clinical visits. Fatigue was measured using the Functional Assessment of Chronic Illness Therapy (FACIT-F) questionnaire. Spearman's correlation (p < 0.05) evaluated FACIT-F against the other clinical measures. Mean FACIT-F was compared between the treatment groups. Multivariate linear regression analysis investigated association between the clinical measures and FACIT-F in more detail. Correlation (p < 0.05) with FACIT-F was the strongest for Health Assessment Questionnaire (HAQ) (r = −0.68), patient global (r = −0.64) and pain (r = −0.62) visual analogue scores. In multivariate models, DAS28, HAQ and pain explained variability in fatigue the best (R 2 = 0.54). Further analyses, looking at the sub components of DAS28, show that fatigue is mainly associated with tender joint counts and pain rather than swollen joint counts or erythrocyte sedimentation rate. RA fatigue levels were not significantly different between patients on no treatment, disease modifying anti-rheumatic drugs or biologics. Fatigue in established RA is not specifically influenced by the type of treatment used but is associated with tender joint counts, pain and disability. This finding is in contrast to recent trials in early RA that suggest biologics are better than traditional disease modifying anti-rheumatic drugs for fatigue. This difference in result may be because the origins of fatigue are not the same in early compared with established RA.


Anti-TNF DAS28 Disease modifying anti-rheumatic drugs Fatigue Rheumatoid arthritis 



DL Scott and G Kingsley receive support for their research from the Arthritis Research Campaign. DL Scott is a National Institute for Health Research Senior Investigator.




  1. 1.
    Wolfe F, Hawley DJ, Wilson K (1996) The prevalence and meaning of fatigue in rheumatic disease. J Rheumatol 23:1407PubMedGoogle Scholar
  2. 2.
    Pinals RS, Masi AT, Larsen RA (1981) Preliminary criteria for clinical remission in rheumatoid arthritis. Arthritis Rheum 24:1308PubMedCrossRefGoogle Scholar
  3. 3.
    Belza BL, Henke CJ, Yelin EH, Epstein WV, Gilliss CL (1993) Correlates of fatigue in older adults with rheumatoid arthritis. Nurs Res 42:93PubMedCrossRefGoogle Scholar
  4. 4.
    Minnock P, FitzGerald O, Bresnihan B (2003) Women with established rheumatoid arthritis perceive pain as the predominant impairment of health status. Rheumatology (Oxford) 42:995CrossRefGoogle Scholar
  5. 5.
    Swain MG (2000) Fatigue in chronic disease. Clin Sci 99:1PubMedCrossRefGoogle Scholar
  6. 6.
    Kirwan JR, Hewlett S (2007) Patient perspective: reasons and methods for measuring fatigue in rheumatoid arthritis. J Rheumatol 34:1171PubMedGoogle Scholar
  7. 7.
    Cella D, Yount S, Sorensen M, Chartash E, Sengupta N, Grober (2005) Validation of the functional assessment of chronic illness therapy fatigue scale relative to other instrumentation in patients with rheumatoid arthritis. J Rheumatol 32:811PubMedGoogle Scholar
  8. 8.
    Furst DE, Schiff MH, Fleischmann RM, Strand V, Birbara CA, Compagnone D, Fischkoff SA, Chartash EK (2003) Adalimumab, a fully human anti-tumor necrosis factor-alpha monoclonal antibody, and concomitant standard antirheumatic therapy for the treatment of rheumatoid arthritis: results of STAR (Safety Trial of Adalimumab in Rheumatoid Arthritis). J Rheumatol 30:2563PubMedGoogle Scholar
  9. 9.
    Cohen SB, Emery P, Greenwald MW, Dougados M, Furie RA, Genovese MC, Keystone EC, Loveless JE, Burmester GR, Cravets MW, Hessey EW, Shaw T, Totoritis MC, REFLEX Trial Group (2006) Rituximab for rheumatoid arthritis refractory to anti-tumor necrosis factor therapy: results of a multi-center, randomized, double-blind, placebo-controlled, phase III trial evaluating primary efficacy and safety at twenty-four weeks. Arthritis Rheum 54:2793PubMedCrossRefGoogle Scholar
  10. 10.
    Smolen JS, Beaulieu A, Rubbert-Roth A, Ramos-Remus C, Rovensky J, Alecock E, Woodworth T, Alten R, OPTION Investigators (2008) Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial. Lancet 371:987PubMedCrossRefGoogle Scholar
  11. 11.
    Keystone EC, Kavanaugh AF, Sharp JT, Tannenbaum H, Hua Y, Teoh LS, Fischkoff SA, Chartash EK (2004) Radiographic, clinical, and functional outcomes of treatment with adalimumab (a human anti-tumor necrosis factor monoclonal antibody) in patients with active rheumatoid arthritis receiving concomitant methotrexate therapy: a randomized, placebo-controlled, 52-week trial. Arthritis Rheum 50:1400PubMedCrossRefGoogle Scholar
  12. 12.
    Mease PJ, Revicki DA, Szechinski J, Greenwald M, Kivitz A, Barile-Fabris L, Kalsi J, Eames J, Leirisalo-Repo M (2008) Improved health-related quality of life for patients with active rheumatoid arthritis receiving rituximab: results of the Dose-Ranging Assessment: International Clinical Evaluation of Rituximab in Rheumatoid Arthritis (DANCER) trial. J Rheumatol 35:20PubMedGoogle Scholar
  13. 13.
    Weinblatt ME, Keystone EC, Furst DE, Moreland LW, Weisman MH, Birbara CA, Teoh LA, Fischkoff SA, Chartash EK (2003) Adalimumab, a fully human anti-tumor necrosis factor alpha monoclonal antibody, for the treatment of rheumatoid arthritis in patients taking concomitant methotrexate: the ARMADA trial. Arthritis Rheum 48:35PubMedCrossRefGoogle Scholar
  14. 14.
    Emery P, Fleischmann R, Filipowicz-Sosnowska A, Schechtman J, Szczepanski L, Kavanaugh A, Racewicz AJ, van Vollenhoven RF, Li NF, Agarwal S, Hessey EW, Shaw TM, DANCER Study Group (2006) The efficacy and safety of rituximab in patients with active rheumatoid arthritis despite methotrexate treatment: results of a phase IIB randomized, double-blind, placebo-controlled, dose-ranging trial. Arthritis Rheum 54:1390PubMedCrossRefGoogle Scholar
  15. 15.
    Mittendorf T, Dietz B, Sterz R, Kupper H, Cifaldi MA, von der Schulenburg JM (2007) Improvement and long term maintenance of quality of life during treatment with adalimumab in severe rheumatoid arthritis. J Rheumatol 34:2343PubMedGoogle Scholar
  16. 16.
    Genovese MC, Becker JC, Schiff M, Luggen M, Sherrer Y, Kremer J, Birbara C, Box J, Natarajan K, Nuamah I, Li T, Aranda R, Hagerty DT, Dougados M (2005) Abatacept for rheumatoid arthritis refractory to tumor necrosis factor alpha inhibition. N Engl J Med 353:1114PubMedCrossRefGoogle Scholar
  17. 17.
    Russell AS, Wallenstein GV, Li T, Martin MC, Maclean R, Blaisdell B, Gajria K, Cole JC, Becker JC, Emery P (2007) Abatacept improves both the physical and mental health of patients with rheumatoid arthritis who have inadequate response to methotrexate treatment. Ann Rheum Dis 66:189PubMedCrossRefGoogle Scholar
  18. 18.
    Westhovens R, Cole JC, Li T, Martin M, Maclean R, Lin P, Blaisdell B, Wallenstein GV, Aranda R, Sherrer Y (2006) Improved health-related quality of life for rheumatoid arthritis patients treated with abatacept who have inadequate response to anti-TNF therapy in a double-blind, placebo-controlled, multi-centre randomized clinical trial. Rheumatology 45:1238PubMedCrossRefGoogle Scholar
  19. 19.
    Yount S, Sorensen MV, Cella D, Sengupta N, Grober J, Chartash EK (2007) Adalimumab plus methotrexate or standard therapy is more effective than methotrexate or standard therapies alone in the treatment of fatigue in patients with active, inadequately treated rheumatoid arthritis. Clin Exp Rheumatol 25:838–846PubMedGoogle Scholar
  20. 20.
    Huyser BA, Parker JC, Thoreson R, Smarr KL, Johnson JC, Hoffman R (1998) Predictors of subjective fatigue among individuals with rheumatoid arthritis. Arthritis Rheum 41:2230PubMedCrossRefGoogle Scholar
  21. 21.
    Pollard LC, Choy EH, Gonzalez J, Khoshaba B, Scott DL (2006) Fatigue in rheumatoid arthritis reflects pain, not disease activity. Rheumatology 45(7):885PubMedCrossRefGoogle Scholar
  22. 22.
    Conaghan PG, Green MJ, Emery P (1999) Established rheumatoid arthritis. Baillieres Best Pract Res Clin Rheumatol 13:561–575PubMedCrossRefGoogle Scholar
  23. 23.
    Wolfe F, Michaud K (2004) Fatigue, rheumatoid arthritis, and anti-tumor necrosis factor therapy: an investigation in 24,831 patients. J Rheumatol 31:2115PubMedGoogle Scholar
  24. 24.
    Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Allaart CF, van Zeben D, Kerstens PJ, Hazes JM, Zwinderman AH, Ronday HK, Han KH, Westedt ML, Gerards AH, van Groenendael JH, Lems WF, van Krugten MV, Breedveld FC, Dijkmans BA (2005) Clinical and radiographic outcomes of four different treatment strategies in patients with early rheumatoid arthritis (the BeSt study): a randomized, controlled trial. Arthritis Rheum 52:3381PubMedCrossRefGoogle Scholar
  25. 25.
    Nikolaus S, Bode C, Taal E, Van de Laar M (2010) Four different patterns of fatigue in rheumatoid arthritis patients: results of a Q-sort study. Rheumatology 49:2191–2199PubMedCrossRefGoogle Scholar
  26. 26.
    Greenwood MC, Rathi J, Hakim AJ, Scott DL, Doyle DV (2007) Regression to the mean using the disease activity score in eligibility and response criteria for prescribing TNF-alpha inhibitors in adults with rheumatoid arthritis. Rheumatology 46:1165–1167PubMedCrossRefGoogle Scholar
  27. 27.
    Cella D, Lai JS, Stone A (2011) Self-reported fatigue: one dimension or more? Lessons from the Functional Assessment of Chronic Illness Therapy—Fatigue (FACIT-F) questionnaire. Support Care Cancer 19(9):1441–1450PubMedCrossRefGoogle Scholar

Copyright information

© Clinical Rheumatology 2011

Authors and Affiliations

  • Richard Charles John Campbell
    • 1
    • 2
    Email author
  • Michael Batley
    • 2
  • Anthony Hammond
    • 2
  • Fowzia Ibrahim
    • 1
  • Gabrielle Kingsley
    • 1
  • David L. Scott
    • 1
  1. 1.Department of RheumatologyKing’s College London School of Medicine, Weston Education CentreLondonUK
  2. 2.Department of RheumatologyMaidstone HospitalMaidstoneUK

Personalised recommendations