TNF and Cowden disease: Two open clinical trials of treating refractory CD with thalidomide showed that clinical response rates were respectively 64% and 70% in 12-week treatment.[8,21] Reviewing 12 cases of refractory CD with different treatments, Plamondon et al[5] found that azathioprine, methotrexate, and anti-TNF-α agents were ineffective but 100 mg/day of thalidomide treatment for 12 months resulted in 75% of average response rate and CD activity index (CDAI) decrease 212 points.