A systematic review by Almeida et al assessing the impact of biologic agents (20 TNF-inhibitors, and 12 non-TNF-inhibitors) on fatigue reported that biologics in patients with active RA can lead to small-to-moderate improvements in fatigue, with similar magnitudes of effect observed for both TNF-inhibitors and other biologic agents [90]. This evidence concerns the gene TNF and rheumatoid arthritis.