OBJECTIVES: Fatigue is a common, distressing symptom of ankylosing spondylitis (AS), a chronic inflammatory disease predominantly affecting the spine. This study evaluated whether adalimumab therapy reduced fatigue in patients with active AS. METHODS: A randomized, placebo-controlled, Phase III study of adalimumab was conducted in Canada with patients with active AS who had experienced an inadequate response to at least one NSAID or disease-modifying, antirheumatic drug (DMARD). Patients received either adalimumab 40 mg every other week or placebo for 24 weeks. Fatigue was assessed by the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), a widely used measure of fatigue in chronic illnesses, and the fatigue item of the BATH AS Disease Activity Index (BASDAI), a well-established instrument used in clinical studies to evaluate AS disease activity. FACIT-F scores range from 0-52, with higher scores representing less fatigue, and a >=3-point change considered clinical meaningful. The BASDAI fatigue item ranges from 0-10, with lower scores reflecting less fatigue. RESULTS: A total of 82 patients (38 on adalimumab, 44 on placebo) were enrolled. At baseline, both arms had comparable demographics and disease characteristics. Baseline FACIT-F (adalimumab 24.4, placebo 23.6) and BASDAI fatigue (adalimumab 6.3, placebo 6.9,) were similar between arms. After 12 weeks, adalimumab patients had achieved statistically significantly greater improvement in FACIT-F than placebo patients (6.9 vs. 1.7, p=0.005). In addition, patients on adalimumab had achieved statistically greater improvement in BASDAI fatigue vs. placebo (-1.7 vs. -0.5, p=0.006). Even greater improvements were achieved at 24 weeks in adalimumab vs. placebo patients for both measures (FACIT-F, 7.8 vs. 2.6, p=0.013, and BASDAI fatigue, -1.9 vs. -0.5, p=0.006). Improvements in FACIT-F at both 12 and 24 weeks were clinical meaningful. CONCLUSIONS: These results indicate adalimumab treatment provides AS patients with statistically significant and clinically meaningful improvements in fatigue compared with placebo.