A Randomized controlled clinical trial on dose optimization of thalidomide in maintenance treatment for recurrent aphthous stomatitis

Abstract Background Recurrent aphthous stomatitis (RAS) is the most common oral mucosal disease, and ulcer‐free periods are a major concern for patients. Thalidomide has been shown to be an effective systemic drug in the treatment of RAS, but the value of undertaking a trial to evaluate various maintenance doses was warranted. Methods We performed this randomized controlled clinical trial with a two‐stage design. Firstly, all the 125 cases of RAS received prednisone at a starting dose of 15 mg/d for one week as an initial therapeutic drug. Secondly, the 100 cases of RAS in the experimental group received thalidomide (50 mg/d vs. 25 mg/d) as a maintenance drug to observe its efficacy and safety. Results During maintenance medication at the fourth and eighth weekend, the two doses (50 and 25 mg/d) of thalidomide were equivalent in reducing the incidence of ulcers, ulcer number, and ulcer pain, respectively (all p > 0.05). Notably, the ulcer‐free period in the group using 25 mg/d thalidomide for eight weeks was longer (mean, >3 months) than those in the other groups (all p < 0.05). Importantly, the total adverse events in the group using 25 mg/d thalidomide were significantly less than those in the group using 50 mg/d ( p < 0.001). Moreover, the effect of 50 mg/d thalidomide on the levels of various salivary cytokines was not superior to 25 mg/d medication ( p > 0.05). Conclusion This dose optimization study concluded that 25 mg/d thalidomide had a long‐term effect on extending the recurrence interval of RAS with better safety.