Background: Thalidomide, a previously banned sedative drug, was rediscovered as an immunomodulator. Multiple studies demonstrated thalidomide as an experimental treatment for refractory Crohn disease. However, the level of evidence has been limited by the overall inconsistent results. With meta-analysis, we aim to assess the effect of thalidomide and its derivative lenalidomide on refractory Crohn disease as well as the adverse event profile.

Methods: MEDLINE, Cochrane Register of Controlled Trials, Cochrane Database of Systemic Reviews, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) were searched in November 2018. All types of peer-reviewed studies in English language were included. Outcomes measures include induction of response; induction of remission; adverse effects.

Results: The search strategy identified 254 articles, of which 24 studies were selected for analysis. A total of 320 adult (age ≥18) and 99 pediatric (age <18) patients were included. Thalidomide induced a clinical response in 217/351 patients (proportion 67.2%, 95% confidence interval [CI] 0.58 to 0.76) and clinical remission in 207/385 patients (proportion 56.7%, 95% CI 0.44 to 0.68); these were associated with younger patient ages (for response, coefficient=-0.0093, p=0.003; for remission, coefficient=-0.0095, p=0.003). In pediatric patients, thalidomide induced clinical response in 74/106 patients (proportion 81.3%, 95% CI 0.66 to 0.93) and clinical remission in 58/97 patients (proportion 68.1%, 95% CI 0.49 to 0.84). Lenalidomide showed no statistical significance in clinical response rate (OR 0.55, 95% CI 0.16 to 1.81) or clinical remission rate (OR 0.29, 95% CI 0.05 to 1.54). Common adverse effects were peripheral neuropathy (32.5%), sedation (28.6%), dermatitis (11.4%), fatigue (3.6%) and dizziness (3.6%).

Conclusions: Thalidomide may not be a reliably effective treatment, particularly in adult patients with refractory Crohn disease. Lenalidomide was not effective for Crohn disease in both adult and pediatric patients.