Thalidomide reduces recurrent GI bleeding in patients with small-intestinal angiodysplasia

Among patients with recurrent gastrointestinal (GI) bleeding due to small-intestinal angiodysplasia (SIA), treatment with thalidomide resulted in fewer bleeding episodes compared with placebo, according to a recent study.

“The results of our previous small, open-label, randomized controlled trial showed that the effects of thalidomide persisted after the initial 4-month treatment period [in patients with refractory bleeding from GI vascular malformations], but confirmatory trials are needed,” said the researchers. [Gastroenterology 2011;141:1629-1637]

Hence, the researchers conducted a double-blind, placebo-controlled, multicentre trial involving 150 patients with SIA and had ≥4 episodes of recurrent bleeding to assess the long-term efficacy and safety of thalidomide. Participants were randomized to receive either thalidomide 100 mg (n=51) or 50 mg (n=49) or placebo (n=50) daily for 4 months. [N Engl J Med 2023;389:1649-1659]

During the 1-year follow-up period after treatment, a significantly higher proportion of patients who received either dose of thalidomide achieved an effective response, defined as ≥50-percent reduction in the number of bleeding episodes, than those who received placebo (68.6 percent [100 mg] and 51.0 percent [50 mg] vs 16.0 percent; p<0.001).

In turn, this has led to fewer bleeding-related hospitalizations in the thalidomide group compared with the placebo group (27.5 percent [100 mg] and 34.7 percent [50 mg] vs 74.0 percent).

Moreover, only 17.6 percent in the 100-mg thalidomide group and 24.5 percent in the 50-mg thalidomide group received a blood transfusion compared with 62.0 percent in the placebo group within the 1-year follow-up period.

The mean change in haemoglobin level was 30.2 and 22.6 g/L with thalidomide 100 and 50 mg, respectively, vs -3.8 g/L with placebo.

During the second follow-up period, more patients in the thalidomide group experienced cessation of bleeding than those in the placebo group (51.0 percent [100 mg] and 32.7 percent [50 mg] vs 4.0 percent).

However, the incidence of adverse events (AEs) was higher in the thalidomide arm than in the placebo arm (68.6 percent [100 mg] and 55.1 percent [50 mg] vs 28.0 percent).

Constipation was the most common AE reported with thalidomide 100 or 50 mg (25.5 percent and 22.4 percent, respectively), followed by somnolence (17.7 percent and 10.2 percent) and peripheral oedema (11.8 percent and 12.2 percent), but all of which “were grade 1 or 2, and either the symptoms resolved or the indicators returned to normal after the end of the treatment period,” the researchers noted.

“Overall, [daily] treatment with thalidomide [for 4 months] was efficacious in the treatment of recurrent bleeding due to SIA but was associated with AEs,” said the researchers.