Thalidomide reduced bleeding in patients with small-intestinal angiodysplasia
A total of 68.6% of patients who were randomized to 100 mg of thalidomide daily (taken in four doses a day) had a reduction of at least 50% in bleeding episodes in the year after treatment compared to 16% of those on placebo.
Treatment with thalidomide reduced bleeding in patients with recurrent bleeding from small-intestinal angiodysplasia (SIA), according to results of a placebo-controlled trial.
Investigators randomized 150 patients to receive an oral daily dose of 100 mg of thalidomide, 50 mg of thalidomide, or a placebo for four months. Median patient age was 62.2 years, and 88% were age 50 years or older. All participants had at least four episodes of bleeding during the previous year due to SIA. Individuals were followed for at least one year after the treatment period. Researchers defined an effective response as a reduction of at least 50% in bleeding episodes in the year after treatment started compared with the year before. Findings from the multicenter double-blind trial, which was carried out in China, were published by The New England Journal of Medicine in November 2023.
A total of 68.6% of patients in the 100-mg group had an effective response, compared with 51% in the 50-mg group and 16% in the placebo group (P<0.001 for simultaneous comparison across the three groups). Incidence of rebleeding was also lowest in the 100-mg group during the four-month treatment period, at 27.5%. In comparison, 42.9% of patients in the 50-mg group experienced rebleeding, as did 90% of patients receiving a placebo. A smaller percentage of patients receiving 100 mg of thalidomide had blood transfusions and were hospitalized for bleeding during the first follow-up period compared with the 50-mg group and placebo group. Treatment with thalidomide was also associated with a shorter length of hospital stay. Adverse events, including constipation, somnolence, limb numbness, and peripheral edema, were more common among patients who took thalidomide.
Because the trial did not include any patients with cardiovascular diseases, findings may not be applicable to these patients, the authors said. In addition, “the thalidomide and placebo tablets were to be taken four times a day, a requirement that may have decreased adherence and may limit generalizability to a more typical group of patients who would be expected to have lower adherence,” they added.
Authors of an accompanying editorial speculated about the potential mechanisms behind thalidomide's efficacy. “The fact that thalidomide was effective during the year after therapy was stopped suggests that thalidomide alters angiodysplasias,” they wrote.
Although the study's results suggest the treatment may be disease-modifying, “many clinicians will still use somatostatin analogues first, 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,” the editorialists concluded.