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Thalidomide for the Treatment of Recurrent Bleeding Owing to Small Intestinal Angiodysplasia
TAKE-HOME MESSAGE
- In this multicenter, double-blind, randomized, placebo-controlled trial involving patients with recurrent bleeding owing to small intestinal angiodysplasias, the effect of a 4-month treatment with thalidomide on bleeding episodes during the treatment period and the following year was studied. During the year following the treatment period, patients who received 100 mg and 50 mg of thalidomide experienced a greater than 50% reduction in bleeding events (68.6% and 51.0%, respectively) compared with a 16.0% reduction noted in patients from the placebo group. Adverse events occurred most frequently in the 100-mg thalidomide group; however, they were all grade 1 or grade 2 in severity.
- The effect of thalidomide on recurrent bleeding owing to small intestinal angiodysplasias presented in this study is promising. Larger studies are needed to confirm these results.
abstract
This abstract is available on the publisher's site.
Access this abstract nowBACKGROUND
Recurrent bleeding from the small intestine accounts for 5 to 10% of cases of gastrointestinal bleeding and remains a therapeutic challenge. Thalidomide has been evaluated for the treatment of recurrent bleeding due to small-intestinal angiodysplasia (SIA), but confirmatory trials are lacking.
METHODS
We conducted a multicenter, double-blind, randomized, placebo-controlled trial to investigate the efficacy and safety of thalidomide for the treatment of recurrent bleeding due to SIA. Eligible patients with recurrent bleeding (at least four episodes of bleeding during the previous year) due to SIA were randomly assigned to receive thalidomide at an oral daily dose of 100 mg or 50 mg or placebo for 4 months. Patients were followed for at least 1 year after the end of the 4-month treatment period. The primary end point was effective response, which was defined as a reduction of at least 50% in the number of bleeding episodes that occurred during the year after the end of thalidomide treatment as compared with the number that occurred during the year before treatment. Key secondary end points were cessation of bleeding without rebleeding, blood transfusion, hospitalization because of bleeding, duration of bleeding, and hemoglobin levels.
RESULTS
Overall, 150 patients underwent randomization: 51 to the 100-mg thalidomide group, 49 to the 50-mg thalidomide group, and 50 to the placebo group. The percentages of patients with an effective response in the 100-mg thalidomide group, 50-mg thalidomide group, and placebo group were 68.6%, 51.0%, and 16.0%, respectively (P<0.001 for simultaneous comparison across the three groups). The results of the analyses of the secondary end points supported those of the primary end point. Adverse events were more common in the thalidomide groups than in the placebo group overall; specific events included constipation, somnolence, limb numbness, peripheral edema, dizziness, and elevated liver-enzyme levels.
CONCLUSIONS
In this placebo-controlled trial, treatment with thalidomide resulted in a reduction in bleeding in patients with recurrent bleeding due to SIA. (Funded by the National Natural Science Foundation of China and the Shanghai Municipal Education Commission, Gaofeng Clinical Medicine; ClinicalTrials.gov number, NCT02707484.).
Additional Info
Disclosure statements are available on the authors' profiles:
Thalidomide for Recurrent Bleeding Due to Small-Intestinal Angiodysplasia
N. Engl. J. Med 2023 Nov 02;389(18)1649-1659, H Chen, S Wu, M Tang, R Zhao, Q Zhang, Z Dai, Y Gao, S Yang, Z Li, Y Du, A Yang, L Zhong, L Lu, L Xu, X Shen, S Liu, J Zhong, X Li, H Lu, H Xiong, Y Shen, H Chen, S Gong, H Xue, Z GeFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
However, there are notable limitations that must be addressed before this study may impact practice in the US. First, thalidomide is highly teratogenic (Category X for pregnancy), and thus requires prescribers to register for a restricted distribution program. The medication is FDA approved for multiple myeloma and erythema nodosum leprosum; therefore, any GI usage would be considered off-label. Second, this study was conducted on a highly selected population, who had reportedly already undergone small-bowel evaluation with capsule endoscopy and/or balloon-assisted enteroscopy. Moreover, in the setting of a clinical trial, there was good compliance with medication and close follow-up (including fecal occult blood tests every 2 weeks), which is not practical in routine clinical practice.
Nonetheless, for patients with transfusion-dependent small-bowel bleeding, there are limited options. After thorough endoscopic evaluation, including capsule endoscopy and possible balloon-assisted enteroscopy, existing ACG guidelines discuss possible octreotide or thalidomide usage. Given risks associated with thalidomide, expert consultation at a tertiary center with GI and hematology would be beneficial, and could allow further prospective trials in the US to help define optimal long-term management of these patients.
Reference
1. Ge ZZ, Chen HM, Gao YJ, et al. Efficacy of thalidomide for refractory gastrointestinal bleeding from vascular malformation. Gastroenterology. 2011;141(5):1629-1637.e1-4. https://www.gastrojournal.org/article/S0016-5085(11)00982-6/fulltext