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, according to results of a new placebo-controlled trial.
At 1 year follow-up, thalidomide doses of 100 mg/day and 50 mg/day outperformed placebo in reducing by at least 50% the number of bleeding episodes, compared with the year prior to treatment, according to the study published online in the New England Journal of Medicine.
SIA, an increasingly recognized cause of repeat obscure gastrointestinal bleeding and iron-deficiency anemia, is a distinct vascular abnormality in the mucosa and submucosa characterized by focal accumulation of ectatic vessels. It is the most common cause of small intestine bleeding, especially among patients older than 50.
There is a high unmet need among patients with SIA for an effective and relatively safe oral medication, given substantial recurrent bleeding risks following endoscopic or surgical procedures, and only observational studies suggest treatment with somatostatin and octreotide, noted senior author Zhizheng Ge, MD, Shanghai Jiao Tong University, Shanghai, China.
SIA is characterized by dilated and tortuous arterial or venous capillaries between thin-walled and immature veins and capillaries without a smooth-muscle layer. Its pathologic process involves chronic hypoxia and vessel sprouting.
Dr. Ge and colleagues postulated that thalidomide’s ability to decrease the expression of proangiogenic factors and angiogenesis would have a long-lasting ameliorating effect on bleeding episodes of angiodysplasia, and thus a continued benefit with respect to bleeding cessation. Their previous small, single-center, open-label, randomized controlled trial of thalidomide for SIA showed a benefit, but it required larger confirmatory trials.
For their current trial, the researchers explored whether a short treatment period, selected to avoid treatment nonadherence, could have a long-term effect. They randomly assigned on a 1:1:1 basis 150 patients with recurrent SIA-related bleeding, defined as at least four episodes during the previous year, to an oral daily dose of 100 mg of thalidomide, 50 mg of thalidomide, or placebo for 4 months.
The patients (median age, 62.2 years; 88% aged 50 years or older) were followed for at least 1 year after treatment. The trial was conducted at 10 sites in China.
The primary endpoint was effective response, defined as a reduction of at least 50% in the number of bleeding episodes in the year following thalidomide treatment, compared with the number in the year before treatment. Bleeding was defined as the presence of overt bleeding or a positive fecal occult blood test.
The percentages of patients with effective response at 1-year follow-up were 68.6% in the 100-mg thalidomide group, 51% in the 50-mg thalidomide group, and 16% in the placebo group.
Among secondary endpoints, the incidence of rebleeding during the 4-month treatment period was 27.5% (14 of 51 patients) in the 100-mg thalidomide group, 42.9% (21 of 49 patients) in the 50-mg thalidomide group, and 90% (45 of 50 patients) in the placebo group. The percentage of patients who received a blood transfusion during the 1-year follow-up period were 17.6% in the 100-mg thalidomide group, 24.5% in the 50-mg thalidomide group, and 62% in the placebo group.
Cessation of bleeding, defined by two consecutive negative fecal occult blood tests on different days, during 1 year of follow-up was observed in 44 patients: 26 (51%) of patients in the 100-mg thalidomide group, 16 (32.7%) in the 50-mg thalidomide group, and 2 (4%) in the placebo group. The authors urge further exploration of the duration of benefit and the efficacy of longer courses of treatment.
Adverse events, all grade 1 or 2, resolved after treatment of symptoms, completion of treatment, or discontinuation of thalidomide or placebo.
Retreatment May Be Necessary
In an accompanying editorial, Loren Laine, MD, chief of the section of digestive diseases, internal medicine, and medical chief, digestive health, Yale School of Medicine, New Haven, Connecticut, affirmed the authors’ conclusions and commended the quality of evidence they provided.
“Their results suggest that thalidomide may be disease-modifying, with efficacy persisting after discontinuation,” wrote Dr. Laine, also a Yale professor of medicine and digestive diseases.
While thalidomide effectively prevented rebleeding for 42 patients during the year after therapy was stopped, suggesting an alteration of angiodysplasias, rebleeding during the subsequent 3-27 months occurred among 20 of those patients, Dr. Laine noted. That finding, “suggests that retreatment will be needed,” although the appropriate duration of treatment before retreatment and the duration of retreatment remain unclear, he added.
The study’s reliance on bleeding episodes that were defined by positive fecal occult blood tests, which may be clinically unimportant, is a weakness in the trial, Dr. Laine wrote.
Despite the study’s positive findings, clinicians may still prefer somatostatin analogues because of their potential for better safety and, with once-monthly injections versus daily thalidomide pills, their likelihood for better adherence, Dr. Laine wrote. “[They] will reserve thalidomide for use in patients who have continued bleeding or side effects with somatostatin analogues,” he added.
Somatostatin is rarely used in the treatment of SIA bleeding in China, where thalidomide is relatively easy to obtain and is being used clinically, Dr. Ge told this news organization in response to Dr. Laine’s editorial. “The clinical application of thalidomide has been taken up in other [Chinese] hospitals that have seen our research,” he added.
Future research may include randomized controlled trials of somatostatin, since Chinese experience with it is so limited, Dr. Ge said. “We would want to compare efficacy, safety, feasibility and cost-effectiveness between somatostatin and thalidomide,” he added.
The study was supported by grants from the National Natural Science Foundation of China and a grant from the Shanghai Municipal Education Commission, Gaofeng Clinical Medicine. The author disclosures can be found with the original article.
, according to results of a new placebo-controlled trial.
At 1 year follow-up, thalidomide doses of 100 mg/day and 50 mg/day outperformed placebo in reducing by at least 50% the number of bleeding episodes, compared with the year prior to treatment, according to the study published online in the New England Journal of Medicine.
SIA, an increasingly recognized cause of repeat obscure gastrointestinal bleeding and iron-deficiency anemia, is a distinct vascular abnormality in the mucosa and submucosa characterized by focal accumulation of ectatic vessels. It is the most common cause of small intestine bleeding, especially among patients older than 50.
There is a high unmet need among patients with SIA for an effective and relatively safe oral medication, given substantial recurrent bleeding risks following endoscopic or surgical procedures, and only observational studies suggest treatment with somatostatin and octreotide, noted senior author Zhizheng Ge, MD, Shanghai Jiao Tong University, Shanghai, China.
SIA is characterized by dilated and tortuous arterial or venous capillaries between thin-walled and immature veins and capillaries without a smooth-muscle layer. Its pathologic process involves chronic hypoxia and vessel sprouting.
Dr. Ge and colleagues postulated that thalidomide’s ability to decrease the expression of proangiogenic factors and angiogenesis would have a long-lasting ameliorating effect on bleeding episodes of angiodysplasia, and thus a continued benefit with respect to bleeding cessation. Their previous small, single-center, open-label, randomized controlled trial of thalidomide for SIA showed a benefit, but it required larger confirmatory trials.
For their current trial, the researchers explored whether a short treatment period, selected to avoid treatment nonadherence, could have a long-term effect. They randomly assigned on a 1:1:1 basis 150 patients with recurrent SIA-related bleeding, defined as at least four episodes during the previous year, to an oral daily dose of 100 mg of thalidomide, 50 mg of thalidomide, or placebo for 4 months.
The patients (median age, 62.2 years; 88% aged 50 years or older) were followed for at least 1 year after treatment. The trial was conducted at 10 sites in China.
The primary endpoint was effective response, defined as a reduction of at least 50% in the number of bleeding episodes in the year following thalidomide treatment, compared with the number in the year before treatment. Bleeding was defined as the presence of overt bleeding or a positive fecal occult blood test.
The percentages of patients with effective response at 1-year follow-up were 68.6% in the 100-mg thalidomide group, 51% in the 50-mg thalidomide group, and 16% in the placebo group.
Among secondary endpoints, the incidence of rebleeding during the 4-month treatment period was 27.5% (14 of 51 patients) in the 100-mg thalidomide group, 42.9% (21 of 49 patients) in the 50-mg thalidomide group, and 90% (45 of 50 patients) in the placebo group. The percentage of patients who received a blood transfusion during the 1-year follow-up period were 17.6% in the 100-mg thalidomide group, 24.5% in the 50-mg thalidomide group, and 62% in the placebo group.
Cessation of bleeding, defined by two consecutive negative fecal occult blood tests on different days, during 1 year of follow-up was observed in 44 patients: 26 (51%) of patients in the 100-mg thalidomide group, 16 (32.7%) in the 50-mg thalidomide group, and 2 (4%) in the placebo group. The authors urge further exploration of the duration of benefit and the efficacy of longer courses of treatment.
Adverse events, all grade 1 or 2, resolved after treatment of symptoms, completion of treatment, or discontinuation of thalidomide or placebo.
Retreatment May Be Necessary
In an accompanying editorial, Loren Laine, MD, chief of the section of digestive diseases, internal medicine, and medical chief, digestive health, Yale School of Medicine, New Haven, Connecticut, affirmed the authors’ conclusions and commended the quality of evidence they provided.
“Their results suggest that thalidomide may be disease-modifying, with efficacy persisting after discontinuation,” wrote Dr. Laine, also a Yale professor of medicine and digestive diseases.
While thalidomide effectively prevented rebleeding for 42 patients during the year after therapy was stopped, suggesting an alteration of angiodysplasias, rebleeding during the subsequent 3-27 months occurred among 20 of those patients, Dr. Laine noted. That finding, “suggests that retreatment will be needed,” although the appropriate duration of treatment before retreatment and the duration of retreatment remain unclear, he added.
The study’s reliance on bleeding episodes that were defined by positive fecal occult blood tests, which may be clinically unimportant, is a weakness in the trial, Dr. Laine wrote.
Despite the study’s positive findings, clinicians may still prefer somatostatin analogues because of their potential for better safety and, with once-monthly injections versus daily thalidomide pills, their likelihood for better adherence, Dr. Laine wrote. “[They] will reserve thalidomide for use in patients who have continued bleeding or side effects with somatostatin analogues,” he added.
Somatostatin is rarely used in the treatment of SIA bleeding in China, where thalidomide is relatively easy to obtain and is being used clinically, Dr. Ge told this news organization in response to Dr. Laine’s editorial. “The clinical application of thalidomide has been taken up in other [Chinese] hospitals that have seen our research,” he added.
Future research may include randomized controlled trials of somatostatin, since Chinese experience with it is so limited, Dr. Ge said. “We would want to compare efficacy, safety, feasibility and cost-effectiveness between somatostatin and thalidomide,” he added.
The study was supported by grants from the National Natural Science Foundation of China and a grant from the Shanghai Municipal Education Commission, Gaofeng Clinical Medicine. The author disclosures can be found with the original article.
, according to results of a new placebo-controlled trial.
At 1 year follow-up, thalidomide doses of 100 mg/day and 50 mg/day outperformed placebo in reducing by at least 50% the number of bleeding episodes, compared with the year prior to treatment, according to the study published online in the New England Journal of Medicine.
SIA, an increasingly recognized cause of repeat obscure gastrointestinal bleeding and iron-deficiency anemia, is a distinct vascular abnormality in the mucosa and submucosa characterized by focal accumulation of ectatic vessels. It is the most common cause of small intestine bleeding, especially among patients older than 50.
There is a high unmet need among patients with SIA for an effective and relatively safe oral medication, given substantial recurrent bleeding risks following endoscopic or surgical procedures, and only observational studies suggest treatment with somatostatin and octreotide, noted senior author Zhizheng Ge, MD, Shanghai Jiao Tong University, Shanghai, China.
SIA is characterized by dilated and tortuous arterial or venous capillaries between thin-walled and immature veins and capillaries without a smooth-muscle layer. Its pathologic process involves chronic hypoxia and vessel sprouting.
Dr. Ge and colleagues postulated that thalidomide’s ability to decrease the expression of proangiogenic factors and angiogenesis would have a long-lasting ameliorating effect on bleeding episodes of angiodysplasia, and thus a continued benefit with respect to bleeding cessation. Their previous small, single-center, open-label, randomized controlled trial of thalidomide for SIA showed a benefit, but it required larger confirmatory trials.
For their current trial, the researchers explored whether a short treatment period, selected to avoid treatment nonadherence, could have a long-term effect. They randomly assigned on a 1:1:1 basis 150 patients with recurrent SIA-related bleeding, defined as at least four episodes during the previous year, to an oral daily dose of 100 mg of thalidomide, 50 mg of thalidomide, or placebo for 4 months.
The patients (median age, 62.2 years; 88% aged 50 years or older) were followed for at least 1 year after treatment. The trial was conducted at 10 sites in China.
The primary endpoint was effective response, defined as a reduction of at least 50% in the number of bleeding episodes in the year following thalidomide treatment, compared with the number in the year before treatment. Bleeding was defined as the presence of overt bleeding or a positive fecal occult blood test.
The percentages of patients with effective response at 1-year follow-up were 68.6% in the 100-mg thalidomide group, 51% in the 50-mg thalidomide group, and 16% in the placebo group.
Among secondary endpoints, the incidence of rebleeding during the 4-month treatment period was 27.5% (14 of 51 patients) in the 100-mg thalidomide group, 42.9% (21 of 49 patients) in the 50-mg thalidomide group, and 90% (45 of 50 patients) in the placebo group. The percentage of patients who received a blood transfusion during the 1-year follow-up period were 17.6% in the 100-mg thalidomide group, 24.5% in the 50-mg thalidomide group, and 62% in the placebo group.
Cessation of bleeding, defined by two consecutive negative fecal occult blood tests on different days, during 1 year of follow-up was observed in 44 patients: 26 (51%) of patients in the 100-mg thalidomide group, 16 (32.7%) in the 50-mg thalidomide group, and 2 (4%) in the placebo group. The authors urge further exploration of the duration of benefit and the efficacy of longer courses of treatment.
Adverse events, all grade 1 or 2, resolved after treatment of symptoms, completion of treatment, or discontinuation of thalidomide or placebo.
Retreatment May Be Necessary
In an accompanying editorial, Loren Laine, MD, chief of the section of digestive diseases, internal medicine, and medical chief, digestive health, Yale School of Medicine, New Haven, Connecticut, affirmed the authors’ conclusions and commended the quality of evidence they provided.
“Their results suggest that thalidomide may be disease-modifying, with efficacy persisting after discontinuation,” wrote Dr. Laine, also a Yale professor of medicine and digestive diseases.
While thalidomide effectively prevented rebleeding for 42 patients during the year after therapy was stopped, suggesting an alteration of angiodysplasias, rebleeding during the subsequent 3-27 months occurred among 20 of those patients, Dr. Laine noted. That finding, “suggests that retreatment will be needed,” although the appropriate duration of treatment before retreatment and the duration of retreatment remain unclear, he added.
The study’s reliance on bleeding episodes that were defined by positive fecal occult blood tests, which may be clinically unimportant, is a weakness in the trial, Dr. Laine wrote.
Despite the study’s positive findings, clinicians may still prefer somatostatin analogues because of their potential for better safety and, with once-monthly injections versus daily thalidomide pills, their likelihood for better adherence, Dr. Laine wrote. “[They] will reserve thalidomide for use in patients who have continued bleeding or side effects with somatostatin analogues,” he added.
Somatostatin is rarely used in the treatment of SIA bleeding in China, where thalidomide is relatively easy to obtain and is being used clinically, Dr. Ge told this news organization in response to Dr. Laine’s editorial. “The clinical application of thalidomide has been taken up in other [Chinese] hospitals that have seen our research,” he added.
Future research may include randomized controlled trials of somatostatin, since Chinese experience with it is so limited, Dr. Ge said. “We would want to compare efficacy, safety, feasibility and cost-effectiveness between somatostatin and thalidomide,” he added.
The study was supported by grants from the National Natural Science Foundation of China and a grant from the Shanghai Municipal Education Commission, Gaofeng Clinical Medicine. The author disclosures can be found with the original article.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE