Introduction
Short bowel syndrome (SBS) is the most common cause of intestinal failure (IF) in children and is generally managed using parenteral nutrition and/or intravenous fluids (PN/IV). Long-term PN/IV can cause potentially life-threatening complications. Patients may receive teduglutide (TED) to encourage adaptation of the remaining intestine and to reduce dependence on PN/IV. Short-term studies have shown that TED is effective and has an acceptable safety profile in children and adults with SBS-associated IF (SBS-IF). However, assessment of long-term treatment with TED in paediatric patients with SBS-IF is limited.
Aims & Methods
We report real-world long-term safety and effectiveness data of TED from a paediatric cohort enrolled in the prospective, multinational SBS Registry (NCT01990040; EUPAS7973). Data were analysed cumulatively for up to 6 years between enrolment and interim data cut-off (June 23, 2014 to June 30, 2023). Patients were categorised based on whether they received TED (ever-treated; received ≥1 dose of TED 0.05 mg/kg/day [median]) or never received TED (never-treated; received PN/IV for ≥6 months before study entry). Safety endpoints included: occurrence of colorectal cancer in patients with any remnant colon; other malignancy; colorectal polyps; and adverse events (AEs). Effectiveness endpoints included clinical response (≥20% reduction in PN/IV volume from baseline) and change from baseline in volume of PN/IV (per weight [L/kg]) and number of days/week receiving PN/IV.
Results
In total, 398 paediatric patients were enrolled: 266 never-treated, 132 ever-treated (per-protocol set, n=397; 266 never-treated, 131 ever-treated). Patients had a mean (standard deviation [SD]) age of 5.4 (4.01) years (ever-treated 6.8 [4.12] years; never-treated 4.8 [3.80] years) and the majority were male (63.7%; ever-treated 68.7%; never-treated 61.3%). The median (range) length of exposure in ever-treated patients was 29.0 (1.15–106.61) months.
No new cases of colorectal cancer or new/worsening colorectal polyps were reported between baseline and interim cut-off. New/worsening malignancies were reported for one never-treated patient. A greater proportion of ever-treated patients reported AEs (87.0% vs 74.4%) and serious AEs (SAEs; 72.5% vs 59.0%) than never-treated patients. AEs and SAEs related to TED were reported in 15.3% and 6.1% of ever-treated patients, respectively. There were no allergic or hypersensitivity reactions to TED. The most common TED-related AEs were vomiting (3.8%) and abdominal pain (2.3%). Fatal events were recorded for one ever-treated and three never-treated patients.
A greater proportion of ever-treated patients had achieved a clinical response (year 1, 18/30, 60.0%; year 3, 11/17, 64.7%) than never-treated patients (year 1, 23/100, 23.0%; year 3, 17/82, 20.7%). Ever-treated patients had a greater mean (SD) reduction from baseline in PN/IV volume (L/kg; ever-treated: year 1, −39.4% [35.97], n=19; year 3, −61.6% [23.64]; n=7; never-treated: year 1, −21.1% [50.70], n=80; year 3, −34.4% [36.83], n=49) and number of days/week receiving PN/IV (ever-treated: year 1, −1.6 [2.16], n=30; year 3, −1.5 [1.77], n=17; never-treated: year 1, −1.0 [2.22], n=100; year 3, −0.6 [1.51]; n=82) than never-treated patients.
Conclusion
This 6-year interim analysis of real-world data from a large cohort of paediatric patients with SBS-IF supports that the safety profile of TED is consistent with the previous 5-year follow-up and suggests that TED improves intestinal adaptation in paediatric patients with SBS-IF over a 3-year period.
Disclosure
Palle B Jeppesen: compensation received from Takeda as a member of the Scientific Advisory Committee for the SBS Registry study; commercial relationships as consultant and speaker with Albumedix, ArTara Therapeutics, Baxter, Coloplast, Ferring Pharmaceuticals, Fresenius Kabi, GLyPharma Therapeutic, Ironwood Pharmaceuticals, Naia Pharmaceuticals, NorthSea Therapeutics, Novo Nordisk Foundation, Protara Therapeutics, Takeda, Therachon, VectivBio and Zealand Pharma.
Martina Kohl-Sobania: compensation received from Takeda as a member of the Scientific Advisory Committee for the SBS Registry study; study investigator for NPS Pharmaceuticals and Takeda; honoraria from Aposan, Takeda and Tauro-Implant as a speaker; advisory board member for Takeda.
Francisca Joly: compensation received from Takeda as a member of the Scientific Advisory Committee for the SBS Registry study; study investigator for NPS Pharmaceuticals, Takeda, VectivBio and Zealand Pharma; advisory board member for Alira Health, ArTara Therapeutics, Baxter, M3E Solutions, Takeda, Therachon, VectivBio and Zealand Pharma; commercial relationships as consultant and speaker for Baxter, B. Braun, Fresenius Kabi, Nestlé Health Sciences, Takeda, Therachon and Théradial.
Joel B Mason: compensation received from Takeda as a member of the Scientific Advisory Committee for the SBS Registry study; research support from Takeda as a site for the study; compensation from Care/of, a producer of nutritional supplements; honoraria from UpToDate, a web-based medical information platform, for authoring chapters.
Johane P Allard: compensation received from Takeda as a member of the Scientific Advisory Committee for the SBS Registry study; fees from Takeda as a consultant and speaker, and research support from Takeda as a study site principal investigator (PI); research support from Fresenius Kabi and OMS as a PI; honoraria from Baxter as a speaker and consultant; research support from Zealand Pharma as a site PI.
Ulrich-Frank Pape: compensation received from Takeda as a member of the Scientific Advisory Committee for the SBS Registry study; honoraria from Takeda as a consultant and speaker, and research support from Takeda, VectivBio and Zealand Pharma as a study site PI.
Loris Pironi: compensation received from Takeda as a member of the Scientific Advisory Committee for the SBS Registry study; advisory board member for Baxter, NorthSea Therapeutics and Takeda.
Gabriel E Gondolesi: speaker for Takeda; compensation received from Takeda as a member of the Scientific Advisory Committee for the SBS Registry study; received investigator-initiated research grant from Takeda.
Lauren K Schwartz: compensation received from Takeda as a member of the Scientific Advisory Committee for the SBS Registry study; speaker for Bristol Myers Squibb; advisory board member for Takeda.
Pinggao Zhang, Sasan Sabrdaran and Yi Wen Huang: employees of Takeda Pharmaceuticals U.S.A., Inc. and receive stock and/or stock options.
André Gabriel: former employee of Takeda Pharmaceuticals U.S.A., Inc. who received stock and/or stock options.
Acknowledgements: This study was funded by Takeda Pharmaceuticals U.S.A., Inc., MA, USA. Medical writing support, funded by Takeda Pharmaceuticals U.S.A., Inc., was provided by Elizabeth Coe, PhD of PharmaGenesis Cardiff, Cardiff, UK.
