Notably, TOF has been shown to treat autoimmune diseases by suppressing the differentiation of pathogenic Th1 and Th17 cells through the inhibition of T-bet and STAT1 activation.[19] Interestingly, owing to the multi-cytokine mechanism involving Th1 and Th17 pathways, therapeutic failure under anti-TNF or anti-IL-6 therapy has been observed in TAK patients resistant to conventional disease-modifying anti-rheumatic drugs.[8] In 13 patients with refractory TAK including 11 treated earlier with biologic agents, 10 had clinical benefits after receiving TOF therapy for 2 to 18 months.[20]. This evidence concerns the gene TNF and autoimmune disease.