https://doi.org/10.4081/reumatismo.2026.2412
Evaluation of the effect of rituximab on fatigue in rheumatoid arthritis using the Chalder Fatigue Scale
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Accepted: 5 October 2026
Published: 28 October 2026
Objective. Fatigue is a frequent extra-articular manifestation of rheumatoid arthritis (RA), with a reported prevalence ranging from 40% to 90%. It affects physical, emotional, and cognitive aspects of daily life and significantly impairs quality of life. Although biologic therapies may improve fatigue, the specific effect of rituximab on this symptom remains insufficiently documented. This study aimed to evaluate the effect of rituximab on fatigue at baseline (M0), 4 months (M4), and 6 months (M6) using the Chalder Fatigue Scale (CFS).
Methods. This prospective, observational, single-center study included patients fulfilling the 2010 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for RA and treated with rituximab. Rituximab was administered as two intravenous infusions (500 mg or 1000 mg) on day 0 and day 15. Fatigue was assessed at M0, M4, and M6 using the CFS, with a score ≥4 indicating clinically significant fatigue. Clinical and biological data were collected at each visit. Statistical analyses were performed using Jamovi version 2.4.14.
Results. Ninety-four patients were included (mean age 57±9 years; 88% female). The median CFS score decreased from 4 [2-6] at M0 to 2 [0-4] at M4 (p<0.001) and remained stable thereafter through M6 (p=0.11 for the M4-M6 comparison). Disease activity improved in parallel, with the Disease Activity Score 28 using C-reactive protein (DAS28-CRP) decreasing from 4.7±1.1 at M0 to 2.9±0.9 at M4 and remaining stable at M6. Functional status assessed by Health Assessment Questionnaire also improved significantly. In multivariable analysis, higher M0 DAS28-CRP was associated with a greater reduction in fatigue.
Conclusions. Rituximab therapy was associated with a significant improvement in fatigue in patients with RA, parallel to reductions in disease activity and functional disability.
Downloads
Druce KL, Jones GT, Macfarlane GJ, Basu N. Patients receiving anti-TNF therapies experience reduced fatigue in rheumatoid arthritis: results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis. Rheumatology 2015; 54: 964-71. DOI: https://doi.org/10.1093/rheumatology/keu390
Nikolaus S, Bode C, Taal E, van de Laar MAFJ. Fatigue and factors related to fatigue in rheumatoid arthritis: a systematic review. Arthritis Care Res 2013; 65: 1128-46. DOI: https://doi.org/10.1002/acr.21949
Hewlett S, Chalder T, Choy E, Cramp F, Davis B, Dures E, et al. Fatigue in rheumatoid arthritis: time for a conceptual model. Rheumatology 2011; 50: 1004-6. DOI: https://doi.org/10.1093/rheumatology/keq282
Pollard LC, Choy EH, Gonzalez J, Khoshaba B, Scott DL. Fatigue in rheumatoid arthritis reflects pain, not disease activity. Rheumatology 2006; 45: 885-9. DOI: https://doi.org/10.1093/rheumatology/kel021
Minnock P, Kirwan J, Bresnihan B. Fatigue is a reliable, sensitive and unique outcome measure in rheumatoid arthritis. Rheumatology 2009; 48: 1533-6. DOI: https://doi.org/10.1093/rheumatology/kep287
van Steenbergen HW, Tsonaka R, Huizinga TWJ, et al. Fatigue in rheumatoid arthritis: a persistent problem. RMD Open 2015; 1: e000041. DOI: https://doi.org/10.1136/rmdopen-2014-000041
Katz P, Margaretten M, Trupin L, Schmajuk G, Yazdany J, Yelin E. Role of sleep disturbance, depression, obesity, and physical inactivity in fatigue in rheumatoid arthritis. Arthritis Care Res 2016; 68: 81-90. DOI: https://doi.org/10.1002/acr.22577
Matcham F, Ali S, Hotopf M, Chalder T. Psychological correlates of fatigue in rheumatoid arthritis: a systematic review. Clin Exp Rheumatol 2015; 33: 305-15. DOI: https://doi.org/10.1016/j.cpr.2015.03.004
van Hoogmoed D, Fransen J, Bleijenberg G, van Riel P. Physical and psychosocial correlates of severe fatigue in rheumatoid arthritis. Rheumatology 2010; 49: 1294-302. DOI: https://doi.org/10.1093/rheumatology/keq043
Tournadre A, Pereira B, Gossec L, Soubrier M, Dougados M. Impact of comorbidities on fatigue in rheumatoid arthritis patients: results from a nurse-led program for comorbidities management (COMEDRA). Joint Bone Spine 2019; 86: 55-60. DOI: https://doi.org/10.1016/j.jbspin.2018.06.010
Almeida C, Choy EH, Hewlett S, Kirwan JR, Cramp F, Chalder T, et al. Biologic interventions for fatigue in rheumatoid arthritis. Cochrane Database Syst Rev 2016; 6: CD008334. DOI: https://doi.org/10.1002/14651858.CD008334.pub2
Pope JE. Management of fatigue in rheumatoid arthritis. RMD Open 2020; 6: e001084. DOI: https://doi.org/10.1136/rmdopen-2019-001084
Edwards JCW, Szczepanski L, Szechinski J, Filipowicz-Sosnowska A, Emery P, Close DR, et al. Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis. N Engl J Med 2004; 350: 2572-81. DOI: https://doi.org/10.1056/NEJMoa032534
van Vollenhoven RF, Emery P, Bingham CO 3rd, Keystone EC, Fleischmann RM, Furst DE, et al. Long-term safety of rituximab in rheumatoid arthritis: 9.5-year follow-up of the global clinical trial programme with a focus on adverse events of interest in RA patients. Ann Rheum Dis 2013; 72: 1496-502. DOI: https://doi.org/10.1136/annrheumdis-2012-201956
Chalder T, Berelowitz G, Pawlikowska T, Watts L, Wessely S, Wright D, Wallace EP. Development of a fatigue scale. J Psychosom Res 1993; 37: 147-53. DOI: https://doi.org/10.1016/0022-3999(93)90081-P
McIlvenny S, Ahmed MH, Dunn E, Swadi H, Balshie M. The translation into Arabic and revalidation of a fatigue questionnaire. East Mediterr Health J 1999; 5: 503-14. DOI: https://doi.org/10.26719/1999.5.3.503
Cohen J. Statistical power analysis for the behavioral sciences. 2nd ed. Hillsdale, NJ, USA: Lawrence Erlbaum Associates; 1988.
Keystone E, Burmester GR, Furie R, Loveless JE, Emery P, Kremer J, et al. Improvement in patient-reported outcomes in a rituximab trial in patients with severe rheumatoid arthritis refractory to anti-tumor necrosis factor therapy. Arthritis Rheum 2008; 59: 785-93. DOI: https://doi.org/10.1002/art.23715
Harrold LR, John A, Best J, et al. Impact of rituximab on patient-reported outcomes in patients with rheumatoid arthritis from the US Corrona Registry. Clin Rheumatol 2017; 36: 2135-40. DOI: https://doi.org/10.1007/s10067-017-3742-2
Gossec L, Danré A, Combe B, Le Loët X, Tebib J, Sibilia J, et al. Improvement in patient-reported outcomes after rituximab in rheumatoid arthritis patients: an open-label assessment of 175 patients. Joint Bone Spine 2015; 82: 451-4. DOI: https://doi.org/10.1016/j.jbspin.2015.02.007
Rigby W, Ferraccioli G, Greenwald M, Zazueta-Montiel B, Fleischmann R, Wassenberg S, et al. Effect of rituximab on physical function and quality of life in patients with rheumatoid arthritis previously untreated with methotrexate. Arthritis Care Res 2011; 63: 711-20. DOI: https://doi.org/10.1002/acr.20419
Goñi M, Basu N, Murray AD, Waiter GD. Brain predictors of fatigue in rheumatoid arthritis: a machine learning study. PLoS One 2022; 17: e0269952. DOI: https://doi.org/10.1371/journal.pone.0269952
Ethics Approval
CRediT authorship contribution
Ilham Ben Marzouk, Imane El Binoune: study conception and design. Ilham Ben Marzouk, Imane El Binoune, Samira Rostom, Hajar Elallagui, Ikram Elmoubarik, Salma Zemrani, Bouchra Amine, Rachid Bahiri: data collection. Kaoutar Dib: statistical analyses (Laboratory of Biostatistics, Clinical Research and Epidemiology – LBRCE, Rabat, Morocco). Ilham Ben Marzouk: first draft of the manuscript. All authors critically revised the manuscript for important intellectual content and approved the final version.
How to Cite
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.
