scholarly journals Teduglutide for the treatment of adults with intestinal failure associated with short bowel syndrome: pooled safety data from four clinical trials

2020 ◽  
Vol 13 ◽  
pp. 175628482090576 ◽  
Author(s):  
Ulrich-Frank Pape ◽  
Kishore R. Iyer ◽  
Palle B. Jeppesen ◽  
Marek Kunecki ◽  
Loris Pironi ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Short Bowel Syndrome ◽  
Safety Profile ◽  
Safety Data ◽  
Intestinal Failure ◽  
Abdominal Distension ◽  
Clinical Trial Registry ◽  
Data Set ◽  
Short Bowel ◽  
Patient Groups

Background: In multiple clinical studies, teduglutide reduced parenteral support (PS) with a consistent safety profile in adults with short bowel syndrome–associated intestinal failure (SBS–IF). The objective of this study was to assess adverse events (AEs) from a pooled data set. Methods: Safety data from four prospective clinical trials of teduglutide in patients with SBS–IF were assimilated. AEs were evaluated in patient groups based on treatment received in each study and in populations stratified to create distinct subgroups based on aetiology, bowel anatomy and baseline PS volume requirements. Results: Safety data are reported for up to 2.5 years, totalling 222 person-years exposure to teduglutide. In most patients, AEs were reported as mild or moderate in severity in all patient groups and occurred at comparable rates between patients who received teduglutide or placebo. Several common gastrointestinal AEs, including abdominal pain, nausea and abdominal distension, were reported more frequently earlier in the course of treatment, with their frequency declining over time. Fewer gastrointestinal AEs were reported in patients with vascular causes of SBS–IF and patients with most of their colon-in-continuity than in other patient subgroups. Across the patient stratification subgroups, the predominant treatment-emergent AEs for which patients receiving teduglutide had a significantly increased relative risk were abdominal distension and gastrointestinal stoma complication compared with patients receiving placebo. Conclusions: Teduglutide had a safety profile consistent with prior adult data and no new safety concerns were identified. The most frequently reported AEs were gastrointestinal in origin, consistent with the underlying disease condition and intestinotrophic actions of teduglutide. Clinical Trial Registry information: NCT00081458/EudraCT, 2004-000438-35; NCT00798967/EudraCT, 2008-006193-15; NCT00172185/EudraCT, 2004-000439-27; NCT00930644/EudraCT, 2009-011679-65

scholarly journals P431 Teduglutide use and nutritional outcomes in short bowel syndrome with intestinal failure: a real-world claims database analysis

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S433-S434
Author(s):  
D Micic ◽  
J Jiang ◽  
L Chen ◽  
T Fan ◽  
F Mu ◽  
...  
Keyword(s):  
Sensitivity Analysis ◽  
Clinical Trials ◽  
Short Bowel Syndrome ◽  
Real World ◽  
Index Date ◽  
Intestinal Failure ◽  
Sensitivity Analyses ◽  
Future Research ◽  
Short Bowel

Abstract Background Teduglutide (TED) is a glucagon-like peptide 2 analogue approved for the treatment of patients with short bowel syndrome (SBS) requiring parenteral support (PS). SBS is a rare condition resulting from a reduced absorptive surface area of the small intestine, most commonly due to inflammatory bowel disease (IBD). Patients with SBS with intestinal failure (SBS-IF) remain dependent on PS to maintain adequate calorie, fluid, electrolyte and micronutrient stability. In phase 3 clinical trials, TED reduced PS requirements in patients with SBS-IF. This study aimed to assess PS use and discontinuation rates among patients with SBS on TED using real-world data. Methods This retrospective cohort study of adults with SBS-IF (≥18 years) with ≥1 TED pharmacy claim(s) used the US-based administrative healthcare claims IBM MarketScan database (2009–2019). The first TED claim was defined as the index date. Patients required ≥6 months of continuous enrolment prior to index date (baseline period) and no history of malignancy. Primary analysis was conducted during the follow-up period (index date to earliest of continuous enrolment end or 2 years post-index). A sensitivity analysis was also conducted among the cohort during the TED utilization period (index date to the earliest of continuous enrolment end or TED discontinuation). Patients required PS use during both baseline and follow-up/TED utilization periods (primary and sensitivity analyses). PS discontinuation was defined as a PS utilization gap of ≥30 days. A generalized estimating equation linear regression model evaluated if PS use (days/week) changed significantly from baseline to selected time points post-index. Results Of 110 identified patients with SBS-IF, mean age was 53.4 (SD 13.2) years and 77 (70%) were women. Included were 51 (46%) patients with Crohn’s disease and 20 (18%) with ulcerative colitis. The main comorbidities were renal disease (23%) and liver disease (15%). PS frequency was 4.6 (2.5), 3.3 (2.9), 2.9 (3.0) and 3.6 (3.0) days/week at baseline and months 6 (p<0.0001), 12 (p<0.0001), and 24 (p=0.0267), respectively. PS discontinuation increased over time to 34.4%, 46.7% and 65.2% at 3, 6, and 12 months, respectively. The sensitivity analysis demonstrated similar rates of PS use and discontinuation. Conclusion In this real-world study of adults with SBS-IF, including >50% with IBD, TED was associated with PS reductions comparable to those achieved in clinical trials and higher PS discontinuation rates even when using a conservative analysis approach. Future research will be required to determine individual predictive factors of PS discontinuation.

PTU-110 Long-Term Safety of Teduglutide Treatment for Patients with Intestinal Failure Associated with Short Bowel Syndrome: Pooled Data from 4 Clinical Trials

Gut ◽  
2016 ◽  
Vol 65 (Suppl 1) ◽  
pp. A109-A110
Author(s):  
SM Gabe ◽  
U-F Pape ◽  
E Delmaestro ◽  
B Li ◽  
NN Youssef ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Short Bowel Syndrome ◽  
Intestinal Failure ◽  
Short Bowel ◽  
Pooled Data

scholarly journals Energy absorption as a measure of intestinal failure in the short bowel syndrome.

Gut ◽  
1989 ◽  
Vol 30 (2) ◽  
pp. 176-183 ◽  
Author(s):  
C A Rodrigues ◽  
J E Lennard-Jones ◽  
D G Thompson ◽  
M J Farthing
Keyword(s):  
Energy Absorption ◽  
Short Bowel Syndrome ◽  
Intestinal Failure ◽  
Short Bowel

scholarly journals Calling for improved quality in the registration of traditional Chinese medicine during the public health emergency: a survey of trial registries for COVID-19, H1N1, and SARS

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Zhuoran Kuang ◽  
◽  
Xiaoyan Li ◽  
Jianxiong Cai ◽  
Yaolong Chen ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Secondary Outcome ◽  
Specific Information ◽  
Clinical Trial Registry ◽  
Data Set ◽  
Diagnosis Criteria

Abstract Objective To assess the registration quality of traditional Chinese medicine (TCM) clinical trials for COVID-19, H1N1, and SARS. Method We searched for clinical trial registrations of TCM in the WHO International Clinical Trials Registry Platform (ICTRP) and Chinese Clinical Trial Registry (ChiCTR) on April 30, 2020. The registration quality assessment is based on the WHO Trial Registration Data Set (Version 1.3.1) and extra items for TCM information, including TCM background, theoretical origin, specific diagnosis criteria, description of intervention, and outcomes. Results A total of 136 records were examined, including 129 severe acute respiratory syndrome coronavirus 2 (COVID-19) and 7 H1N1 influenza (H1N1) patients. The deficiencies in the registration of TCM clinical trials (CTs) mainly focus on a low percentage reporting detailed information about interventions (46.6%), primary outcome(s) (37.7%), and key secondary outcome(s) (18.4%) and a lack of summary result (0%). For the TCM items, none of the clinical trial registrations reported the TCM background and rationale; only 6.6% provided the TCM diagnosis criteria or a description of the TCM intervention; and 27.9% provided TCM outcome(s). Conclusion Overall, although the number of registrations of TCM CTs increased, the registration quality was low. The registration quality of TCM CTs should be improved by more detailed reporting of interventions and outcomes, TCM-specific information, and sharing of the result data.

Intestinal Failure and Short Bowel Syndrome

Medicine ◽  
2003 ◽  
Vol 31 (3) ◽  
pp. 98-100 ◽  
Author(s):  
Alastair Forbes
Keyword(s):  
Short Bowel Syndrome ◽  
Intestinal Failure ◽  
Short Bowel

Fecal Microbiome and Bile Acid Metabolome in Adult Short Bowel Syndrome

2021 ◽  
Author(s):  
Harold J. Boutte ◽  
Jacqueline Chen ◽  
Todd N. Wylie ◽  
Kristine M. Wylie ◽  
Yan Xie ◽  
...  
Keyword(s):  
Bile Acid ◽  
Gut Microbiota ◽  
Short Bowel Syndrome ◽  
Lithocholic Acid ◽  
Intestinal Failure ◽  
Patient Specific ◽  
Rrna Gene ◽  
Healthy Controls ◽  
Fecal Microbiome ◽  
Short Bowel

Background & Aims: Loss of functional small bowel surface area causes short bowel syndrome (SBS), intestinal failure, and parenteral nutrition (PN) dependence. The gut adaptive response following resection may be difficult to predict, and it may take up to two years to determine which patients will wean from PN. Here we examined features of gut microbiota and bile acid (BA) metabolism in determining adaptation and ability to wean from PN. Methods: Stool and sera were collected from healthy controls and from SBS patients (n=52) with ileostomy, jejunostomy, ileocolonic and jejunocolonic anastomoses fed with PN plus enteral nutrition or who were exclusively enterally fed. We undertook 16S rRNA gene sequencing, BA profiling and 7α-hydroxy-4-cholesten-3-one (C4) quantitation with LC-MS/MS, and serum amino acid analyses. Results: SBS patients exhibited altered gut microbiota with reduced gut microbial diversity compared to healthy controls. We observed differences in the microbiomes of SBS patients with ileostomy vs. jejunostomy, jejunocolonic vs. ileocolonic anastomoses, and PN-dependence compared to those who weaned from PN. Stool and serum BA composition and C4 concentrations were also altered in SBS patients, reflecting adaptive changes in enterohepatic BA cycling. Stools from patients who weaned from PN were enriched in secondary BAs including deoxycholic acid and lithocholic acid. Conclusions: Shifts in gut microbiota and BA metabolites may generate a favorable luminal environment in select SBS patients, promoting the ability to wean from PN. Pro-adaptive microbial species and select BA may provide novel targets for patient-specific therapies for SBS.

scholarly journals Measurement of Utilities Associated with Parenteral Support Requirement in Patients with Short Bowel Syndrome and Intestinal Failure

2018 ◽  
Vol 40 (11) ◽  
pp. 1878-1893.e1 ◽  
Author(s):  
Rachel Ballinger ◽  
Jake Macey ◽  
Andrew Lloyd ◽  
John Brazier ◽  
Joanne Ablett ◽  
...  
Keyword(s):  
Short Bowel Syndrome ◽  
Intestinal Failure ◽  
Short Bowel ◽  
Parenteral Support

scholarly journals Long-Term Safety Profile of the Oral Spleen Tyrosine Kinase Inhibitor Fostamatinib in Immune Thrombocytopenia (ITP) and Other Diseases

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 35-36
Author(s):  
Sandra Tong ◽  
Robert P. Numerof ◽  
Jane Datangel ◽  
Esteban Masuda
Keyword(s):  
Tyrosine Kinase ◽  
Safety Profile ◽  
Safety Data ◽  
First Year ◽  
Patient Exposure ◽  
Publicly Traded ◽  
Data Set ◽  
Pooled Data ◽  
The Mean

Introduction: Fostamatinib is an oral, potent inhibitor of spleen tyrosine kinase (SYK) with proven efficacy and a manageable safety profile for the treatment of ITP. SYK is situated in an intracellular signaling pathway upstream of Bruton's tyrosine kinase (BTK). Long-term safety data on fostamatinib at various dosing regimens (up to 150 mg BID) has been collected in >4000 patients with ITP, rheumatoid arthritis (RA), and other autoimmune, allergic and neoplastic disorders. The safety and tolerability of fostamatinib were consistent across different patient populations (apart from disease specific events). We present a summary analysis of the fostamatinib safety data from the ITP and RA studies. Methods: Fostamatinib safety data from 2 randomized, double-blind, placebo-controlled, phase 3 studies and the long-term, open-label, extension (OLE) study in ITP were pooled and are based on a starting dose of 200 mg/day, which was increased to 300 mg/day after 4 weeks in 88% of patients. Fostamatinib safety data from 13 phase 2/3 studies in RA were pooled and are based on a dosing regimen of 100-150 mg/day (n=1232) or 200-300 mg/day (n=2205). Results: The pooled data set for ITP included 146 patients; 60% were female, and the median age was 53 years (range 20-88). The mean duration of fostamatinib treatment was 19 months (range <1-62 months), representing 229 patient exposure years. Adverse events (AEs) were reported in 87% of patients, and 63% were mild to moderate. Serious AEs were reported in 31% of patients. The incidence of diarrhea, hypertension, alanine aminotransferase increase (ALT), and aspartate aminotransferase (AST) increase was evaluated in 58 patients who received fostamatinib for ≥1 year. This enabled a comparison of the incidence of these AEs in quartiles over the first year to assess the cumulative effects of fostamatinib. The AEs were reported with decreasing frequency during the second, third, and fourth quarters of fostamatinib treatment compared with the first quarter of the initial year of treatment in the 58 patients (see Figure 1). In the same 58 patients, the use of rescue therapy decreased while median platelet counts increased each quarter of the first year. The pooled data set for RA included 3437 patients who received fostamatinib; 83% were female, and the median age was 54 (range 18 -87). The mean duration of treatment was 18 months (range <1-81) representing 5134 patient exposure years. AEs were reported in 86% of RA patients and were mild to moderate in 73% of RA patients. Serious AEs occurred in 14%. In the placebo-controlled RA studies, 2414 patients received fostamatinib with 823 patient exposure years and 1169 received placebo with 367 patient exposure years. Despite a two-fold (125%) increase in exposure with fostamatinib vs placebo (823 vs 367 patient exposure years), there was only a 26% increase in AEs with fostamatinib vs placebo (68% vs 54%). The most common events in the ITP and RA studies were diarrhea (36% and 24%), hypertension (22% and 19%) and nausea (19% and 8%), apart from disease-related AEs. Epistaxis (19% and 0.5%), petechiae (15% and 0.3%), contusion (12% and 2%), and fatigue (10% and 2%) are associated with ITP and were uncommon in the RA population. Rheumatoid arthritis was reported as an AE in 9% of patients with RA and in none with ITP. Some AEs may be dose-related, and one-third of the RA patients were on lower dosages (100-150 mg/day) than were generally given in the ITP trials (200-300 mg/day). Conclusions: Fostamatinib has been evaluated in >4000 patients across different disease populations. Fostamatinib has a consistent and manageable safety profile. No new safety signals and no cumulative toxicity were observed with up to 81 months (6.8 years) of continuous treatment. Figure 1 Disclosures Tong: Rigel: Current Employment, Current equity holder in publicly-traded company. Numerof:Rigel: Current Employment, Current equity holder in publicly-traded company. Datangel:Rigel: Current Employment, Current equity holder in publicly-traded company. Masuda:Rigel: Current Employment, Current equity holder in publicly-traded company.

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