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Endocrine Abstracts (2020) 72 P1 | DOI: 10.1530/endoabs.72.P4


Telotristat in the management of Carcinoid diarrhoea – real world experience of patients from an ENETs centre of excellence in Neuroendocrine tumours.

Amardeep Khanna1,2,3, Nicole Cianci4, Husnain Abbas Shah4, Ashish Goel4, Asma Jebril4, Jessica Chauhan4, Michelle Pipe4, Shishir Shetty44,5, Christopher Weston5, Hema Venkataraman4, Stacey Smith4, Suzanne Vickrage4, Joanne Kemp-Blake4 & Tahir Shah4


1Institute of Liver Sciences, Kings College Hospital, London, UK; 2Liver Unit, Queen Elizabeth Hospital, Birmingham, UK; 3Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK; 4University Hospitals Birmingham, Birmingham, UK; 5Institute of Immunology and Immunotherapy, Birmingham University, Birmingham, UK

Carcinoid syndrome occurs in 20% patients, presenting with flushing, abdominal pain, diarrhoea, and wheeze and can be challenging to manage. The standard of care for carcinoid syndrome is somatostatin analogues (SSAs) with add-on Creon, codeine and loperamide therapy. Nonetheless, half of patients experience debilitating diarrhoea. Telotristat-ethyl is a peripheral tryptophan-hydroxylase inhibitor approved for treatment of diarrhoea, supported by Phase 3 clinical trials but lacking in real-world data. Here we present our experience on effectiveness of Telotristat on carcinoid diarrhoea in the largest cohort of patients outside a clinical trial. The primary outcome was reduction in stool frequency (number/day) of >30%, as defined in most studies. Data was collected retrospectively from an electronic database. We included 31 patients (25M, 6F; Median age 69 (45–85) years) {study group} on Telotristat and 10 patients on maximum dose of 2 weekly SSAs but no Telotristat (6M, 4F; Median age 67 (49–79) years) {control group}. The mean (range) duration of treatment in each group was 258 (15–479) and 689 (219–1446) days, respectively. Primary end-point was achieved in 82% (23/28) patients on Telotristat with median-percentage reduction stool frequency of 60% (IQR 50–69), compared to 28% (2/7) (22 (-30 to 55)%) in the control group, (OR-11, 95% CI 1.71–77.1). The pre and post values were compared by Wilcoxon signed rank test. There was a statistically significant change in pre and post stool frequency in Telotristat group {5(3–60) to 2(1–2.5), P<0.01}. A significant reduction in Urinary 5-hydroxyindoleacetic acid (5-HIAA) was noted in the Telotristat group (n=28) {740 (342–1462) to 334 (125–709) μmol/24 h, P<0.001}. Interestingly, change in stool frequency did not correlate with delta HIAA (ρ:027, P=0.2). The delta change in stool frequency between the two groups was significant (P=0.04). No significant difference (P=0.185 (Fisher’s exact test)} in mortality was seen between Telotristat {16% (5/31)} and the control group {40% (4/10)}. One patient discontinued Telotristat due to mood changes, which reversed after stopping the drug. In conclusion, our real-world study supports the effectiveness and safety of Telotristat to treat carcinoid diarrhoea in patients not responsive to SSA.

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