Other agents used in the case of GC failure or the development of adverse side effects due to MTX include AZA [41], leflunomide (LEF) [28], MMF [42,43], and cyclophosphamide (CYC) [44], as well as the newer TNF-alpha inhibitors, especially infliximab and adalimumab, which have recently been shown to be effective as GC-sparing therapies in refractory cases of CS [39,45]. The gene discussed is TNF; the disease is Cowden syndrome 1.