Effect of Etanercept on Fatigue in Patients With Recent or Established Rheumatoid Arthritis LARRY W. MORELAND, 1 MARK C. GENOVESE, 2 REIKO SATO, 3 AND AMITABH SINGH 3 Objective. To assess the long-term impact of etanercept on fatigue in patients with recent-onset (mean duration 11 months) or established (mean duration 12 years) rheumatoid arthritis (RA). Methods. Patients participating in either of 2 multicenter, randomized, double-blind clinical trials were included. In one trial, patients with recent-onset RA received either etanercept 25 mg twice weekly or methotrexate in a double-blind fashion for 12 months, then open label for 12 months. All patients then received open-label etanercept. In the second trial, patients with established RA received etanercept 25 mg or placebo twice weekly for 6 months in a double-blinded fashion, then open-label etanercept. Up to 46 months of followup data were included. Fatigue was measured regularly using the Health Assessment Questionnaire vitality domain. Results. Patients with recent-onset RA who received etanercept had a significantly faster improvement in fatigue than those receiving methotrexate in the first 2 months. Subsequently, patients receiving etanercept and methotrexate had 23–29% and 17–24% reductions in fatigue scores, respectively. In the group with established RA, patients who received etanercept had significantly greater reductions in fatigue than those receiving placebo during the blinded period. Patients initially receiving etanercept sustained a mean fatigue reduction of 25–36% for the entire followup. Patients achieving clinically meaningful improvement in fatigue were more likely to meet the American College of Rheumatology improve- ment criteria. Conclusion. Etanercept therapy reduces fatigue in patients with recent-onset or established RA. Improvement in fatigue was sustained for up to 46 months, and correlated with other RA-relevant outcomes. KEY WORDS. Rheumatoid arthritis; Fatigue; Vitality; Quality of life; Etanercept; Methotrexate; Health Assessment Questionnaire; Short Form 36. INTRODUCTION Rheumatoid arthritis (RA) is an autoimmune disease in which synovial joints, commonly the wrists, knees, and joints in the hands and feet, are chronically inflamed (1). As the disease progresses, the structure of affected joints is damaged and the joints may become deformed (1,2). RA has a considerable impact on the patient’s quality of life (3), and is associated with substantial pain, gradual loss of mobility, and inability to care for oneself (1). On average, patients with RA have impaired psychological and social functioning and commonly experience anxiety and de- pression (3,4). Fatigue is another common symptom of RA that has considerable impact on quality of life. In one study, pa- tients with RA reported higher fatigue levels than age- and sex-matched controls (5). One study involving 628 pa- tients with RA found that 87% reported feeling fatigued; in 42% of patients, this fatigue was considered by investiga- tors to be clinically important (6). In another study, 69% of 446 patients reported feeling severely or very severely fatigued (7). Interviews have revealed that relief of fatigue is one of the outcomes most desired by patients with RA (7,8). In addition, fatigue level has been reported to be more predictive of quality of life than pain, joint tender- ness, or disease activity (4). Although the etiology of RA is not well understood, increased fatigue correlates with pain, depression, anxiety, stress, self efficacy, and well-intentioned but unhelpful social support (5,9 –13). Fatigue does not correlate well with objective measures of disease activity, such as num- ber of swollen joints or erythrocyte sedimentation rate, Supported by Wyeth Research and Amgen, Inc. 1 Larry W. Moreland, MD: University of Alabama at Bir- mingham, Birmingham; 2 Mark C. Genovese, MD: Stanford University School of Medicine, Palo Alto, California; 3 Reiko Sato, PhD, Amitabh Singh, PhD: Wyeth Research, Colle- geville, Pennsylvania. This article was prepared with the assistance of BioMed- Com Consultants Inc, Montreal, Canada. Address correspondence to Amitabh Singh, PhD, Wyeth Research, 500 Arcola Road, Collegeville, PA 19426. E-mail: singha2@wyeth.com. Submitted for publication August 25, 2004; accepted in revised form September 8, 2005. Arthritis & Rheumatism (Arthritis Care & Research) Vol. 55, No. 2, April 15, 2006, pp 287–293 DOI 10.1002/art.21838 © 2006, American College of Rheumatology ORIGINAL ARTICLE 287