Thalidomide for refractory gastrointestinal bleeding from vascular malformations in patients with significant comorbidities

Abstract

BACKGROUND Refractory gastrointestinal bleeding (GIB) secondary to gastrointestinal vascular malformations (GIVM) such as gastrointestinal angiodysplasia (GIAD) and gastric antral vascular ectasia (GAVE) remains challenging to treat when endoscopic therapy fails. Recently thalidomide has been suggested as a treatment option for refractory GIB. AIM To determine the outcome of patients treated with thalidomide for refractory GIB due to GIVM. METHODS IRB approved, single center, retrospective review of electronic medical records from January 2012 to November 2018. Patients age > 18 years old, who had > 3 episodes of GIB refractory to medical or endoscopic therapy, and who had been treated with thalidomide for at least 3 mo were included. The primary endpoint was recurrence of GIB 6 mo after initiation of thalidomide. RESULTS Fifteen patients were included in the study, all with significant cardiac, hepatic, or renal comorbidities. The cause of GIB was GIAD in 10 patients and GAVE in 5 patients. Two patients were lost to follow up. Of the 13 patients followed, 38.5% ( n = 5) had no recurrent GIB or transfusion requirement after treatment with thalidomide. Furthermore, 84.6% ( n = 11) of patients had a reduction in transfusion requirements and hospitalizations for GIB. Thalidomide was discontinued in 2 patients due to cost ( n = 1) and medication interaction ( n = 1). Reported adverse reactions included fatigue ( n = 3), neuropathy ( n = 2), dizziness ( n = 1), and constipation ( n = 1). Six patients died during follow up due to unknown cause ( n = 4) and sepsis ( n = 2). CONCLUSION Thalidomide appears to be an effective treatment for refractory GIB due to GIAD or GAVE in a Western population with significant comorbidities.

A drug repositioning success: The repositioned therapeutic applications and mechanisms of action of thalidomide

“…Thalidomide has been used successfully to control recurrent, gastrointestinal bleeding or refractory bleeding from angiodysplasias. 6,32…”

Thalidomide for prevention of camrelizumab‐induced reactive cutaneous capillary endothelial proliferation

“…Thalidomide has now re-emerged as a treatment of multiple myeloma, erythema nodosum leprosum, bleeding caused by gastrointestinal vascular malformation and chemotherapy-induced nausea and vomiting. [13][14][15][16] Since thalidomide has been proved to be an effective antiangiogenic drug in the treatment of malignant tumours, we hypothesised that it can decrease the incidence of RCCEP in patients who received camrelizumab therapy. To our knowledge, no studies had explored thalidomide as a therapy for RCCEP induced by camrelizumab; therefore, we conducted this study to evaluate the effection of thalidomide on RCCEP.…”

“…Thalidomide is an agent with antiangiogenic activity; however, in early 1960s, thalidomide was withdrawn from the market due to its serious teratogenic effects. Thalidomide has now re‐emerged as a treatment of multiple myeloma, erythema nodosum leprosum, bleeding caused by gastrointestinal vascular malformation and chemotherapy‐induced nausea and vomiting 13–16 . Since thalidomide has been proved to be an effective antiangiogenic drug in the treatment of malignant tumours, we hypothesised that it can decrease the incidence of RCCEP in patients who received camrelizumab therapy.…”

Efficacy of pharmacologic treatment for treating gastrointestinal angiodysplasias-related bleeding: a systematic review and meta-analysis

“…lww.com/EJGH/A767). When excluding studies enrolling patients with GAVE [33,34,38], the pooled rebleeding rate post-treatment did not differ from the initial meta-analytic outcome [31% (95% CI, 22-39%)].…”

“…For studies where follow-up exceeded 24 months [31,37,38], the meta-analytic outcome also remained significant [OR (95% CI), 0.18 (0.08-0.44; I 2 = 29%; P = 0.24; Supplementary Appendix 3 Figure 2, Supplemental digital content 1, http://links.lww.com/ EJGH/A767). When excluding studies evaluating bevacizumab [11][12][13]33], no difference was detected [rebleeding rate before and after administration of pharmacologic treatment: OR, 0.08 (0.03-0.19), pooled rebleeding rate: 32% (23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40).…”