Here, we have demonstrated that an anti-hTNF-α VNAR construct (Quad-XTM) previously reported as having potent in vitro activity (24) retains this superiority to the commercially available blockbuster anti-TNF-α, Adalimumab (Humira®) in vivo and is capable of preventing the development of spontaneous polyarthritis in a transgenic mouse model of arthritis at doses below 3 mg/kg. Here, TNF is linked to polyarticular arthritis.