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Treatment with thalidomide led to a reduction in bleeding among patients with recurrent bleeding due to small-intestinal angiodysplasia (SIA), a randomized trial showed.

In 150 patients, 68.6% of those who received 100-mg thalidomide daily for 4 months experienced a reduction of 50% or more in bleeding episodes in the year after treatment compared with 51% of those who received 50-mg thalidomide and 16% of those who received placebo (P<0.001 for comparison across the three groups), reported Huimin Chen, MD, of Shanghai Jiao-Tong University in China, and colleagues.

Secondary endpoints also supported the efficacy of thalidomide; for example, 28% of patients in the 100-mg group were hospitalized for re-bleeding in the year after treatment compared with 35% of those in the 50-mg group and 74% in the placebo group (P<0.001), they noted in the .

"Other secondary endpoints, including the number of bleeding episodes, the duration of bleeding, the hemoglobin level, and the percentage of patients who had cessation of bleeding without re-bleeding, were directionally consistent," Chen and team wrote.

"There is an unmet medical need for an effective and relatively safe oral medicine to treat recurrent bleeding due to SIA," they noted, adding that rates of re-bleeding are high after endoscopic treatment, and the evidence supporting somatostatin analogues is limited.

A showed that thalidomide decreases the expression of proangiogenic factors, including vascular endothelial growth factor, angiopoietin 2, notch 1, and delta-like ligand 4 in patients with angiodysplasia.

In an , Loren Laine, MD, of Yale School of Medicine in New Haven, Connecticut, said Chen's group provided higher-quality evidence for thalidomide than is available for any other therapy for this indication. "In addition, their results suggest that thalidomide may be disease-modifying, with efficacy persisting after discontinuation," he wrote.

The appropriate dose of thalidomide, however, is not clear, he noted. "Clinicians may administer 50 mg, 100 mg, or 50 mg initially, with an increase to 100 mg on the basis of clinical response and side effects," he suggested.

"Many clinicians will still use somatostatin analogues first," Laine added, "given the potential for better adherence (once-monthly injections vs daily pills) and safety, and will reserve thalidomide for use in patients who have continued bleeding or side effects with somatostatin analogues."

For this multicenter double-blind study, Chen's group randomized 150 patients 1:1:1 to receive an oral dose of 100 mg thalidomide daily (25-mg tablets four times per day), 50 mg daily (25-mg tablets twice daily plus two placebo tablets), or four placebo tablets daily. Treatment lasted for 4 months. The patients were followed for 1 year before and after treatment to assess outcomes.

All patients in the study experienced at least four bleeding episodes in the year before treatment. The primary endpoint was a reduction of at least 50% in bleeding episodes in the year after treatment.

The median age of study participants was 62, and most (88%) were 50 and older. Slightly more than half (59%) were women. The trial was conducted from April 2016 through December 2020 at 10 sites in China.

Adverse events were more common in the thalidomide groups than in the placebo group. Specific events included constipation, somnolence, limb numbness, peripheral edema, dizziness, and elevated liver-enzyme levels.

Laine noted that the study included patients with bleeding episodes that were defined solely by positive fecal occult blood tests, which may not be clinically important. However, less than 20% of the bleeding episodes were occult, and an analysis that excluded occult bleeding episodes yielded findings similar to those of the main analysis.

The researchers noted other limitations. The study's sample sizes were too small to adequately compare the two doses of thalidomide. In addition, the trial lacked racial and ethnic diversity: all participants were Han Chinese. "The results of the current trial need to be further confirmed in non-Han Chinese populations," they wrote.

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