Long-term data support teduglutide safety for SBS-IF

In a pooled analysis of two long-term paediatric extension trials evaluating short bowel syndrome-associated intestinal failure (SBS-IF), the glucagon-like peptide-2 analogue teduglutide (TED) demonstrated a safety profile that aligned with previous data.

“[Our study has] shown that teduglutide was safe. The safety profile was consistent over 144 weeks. There was a sustained long-term reduction in parenteral nutrition and/or intravenous fluids (PN/IV),” said Dr Susan Hill from the Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK, during her presentation at ESPGHAN 2023.

The two original trials were long-term studies evaluating TED in paediatric patients with SBS-IF. In one study, patients had a ‘break’ period wherein they did not receive any TED before being offered to participate in the longer-term study. In both studies, participants received the approved TED treatment dose (0.05 mg/kg/day). But in the parent studies, some participants received lower doses of TED (0.0125 or 0.025 mg/kg/day).

The pooled cohort had three arms: any TED, TED/TED, and NTT/NTT* (n=78, 69, and 7, respectively). Among TED recipients, median age was 4 years, 68 percent were boys, and median residual small intestine length was 30 cm. [ESPGHAN 2023, abstract N-O037]

“There were no new treatment-emergent adverse events (TEAEs) compared with the original studies,” Hill said. TEAEs were evaluated through the 144-week period (~3 years).

Overall, the most common TEAE among those who received any TED dose was vomiting (54 percent). “Other common AEs were fever, cough, and upper respiratory tract infections,” noted Hill.

Growth parameters remained stable through 144 weeks, with no significant changes in weight, height, and BMI, as well as in head circumference among participants aged <2 years.

By week 96, mean percent change in prescribed PN/IV volume dropped in the TED/TED arm (–50.3 percent), as did the mean percent change in prescribed PN/IV energy intake (–46.3 percent).

Moreover, 84 percent of participants in the TED/TED arm achieved clinical response by week 96, while 22 percent acehived enteral autonomy.

On multivariate analysis, non-White race (parameter estimate [PE], –6.38), older age at baseline (PE, –1.11), longer TED exposure (PE, –0.09), and increasing residual small intestine length (PE, –0.04; p<0.001 for all) were all tied to a significant reduction in PN/IV volume requirements.

“Long-term dependence on PN/IV can lead to life-threatening complications. [Our findings showed that] treatment with TED resulted in a sustained, long-term reduction of PN/IV requirements,” said Hill.

This is the longest and largest study to date, and the pooling of long-term data increased the sample size for statistical analysis, Hill noted. However, the study might have been limited by the lack of a control arm and the small number of patients in the NTT group. “Also, we cannot be entirely clear about the contribution of spontaneous intestinal adaptation. Some patients also had interrupted/intermittent exposure to TED.”

“We need to develop some clinical algorithms that can predict which patients might benefit from treatment. We need to work out the duration of treatment that is necessary for achieving an optimal response and whether we can safely stop treatment in some patients,” Hill concluded.