From the AGA Journals

Teduglutide cut parenteral intake at 52 weeks


 

FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY

Two-thirds of patients with short bowel intestinal failure who took teduglutide reduced their parenteral nutrition intake by 20% or more, for an average reduction of 5 L of parenteral nutrition per week.

Moreover, once-daily dosing was safe and effective, reported Dr. Stephen J.D. O’Keefe and his coauthors in the July issue of Clinical Gastroenterology and Hepatology.

According to the authors, teduglutide, a glucagon-like peptide-2 analogue, produces villous hypertrophy, retards gastric secretion and emptying, and increases mucosal blood flow and absorption.

Source: American Gastroenterological Association

In a 28-week extension study of an initial 24-week, double-blind, randomized controlled trial of teduglutide, Dr. O’Keefe, of the University of Pittsburgh, looked at adult patients with small bowel intestinal failure caused by intestinal resection.

All patients were dependent on parenteral nutrition (PN) or fluid and electrolytes at least 3 times per week, for at least 12 months before the start of the study.

Antimotility and antidiarrheal agents were permitted, but only if their use was stable for 4 or more weeks prior to study baseline.

At the start of the study, published online in January (doi: 10.1016/j.cgh.2012.12.029), all patients’ fluid intakes were optimized to maintain a urine output of between 1 and 2 L daily, with stable blood creatinine concentrations and a urine sodium content of at least 20 mEq/L.

Patients were then randomized to receive subcutaneous, once-daily injections of teduglutide (dosed at either 0.05 or 0.10 mg/kg per day) or placebo.

The 56 patients who received the drug in the initial 24-week study (Gut 2011;60:902-14) were then invited to participate in a 28-week extension trial. Of these, 52 agreed (25 patients taking 0.05 mg/kg per day and 27 patients taking 0.10 mg/kg per day).

By 52 weeks, 68% of patients in the teduglutide 0.05-mg/kg per day group and 52% of patients in the 0.10-mg/kg per day group were responders, defined as achieving the endpoint of reductions of 20% or greater of baseline PN volume, according to the authors.

Indeed, the authors reported that patients on teduglutide 0.05 mg/kg per day decreased their PN volume by 4.9 L/week (52%), while patients taking teduglutide 0.10 mg/kg per day decreased their PN volume by 3.3 L/week (26%).

Four subjects in the study were completely weaned from PN. "Three patients in the teduglutide 0.05-mg/kg per day treatment group became completely independent of PN after 25, 2, and 6.5 years [of parenteral support], receiving 5.4, 3.5, and 12.0 L/d parenteral support per week at baseline, respectively," wrote the authors. "Another patient receiving the teduglutide 0.10-mg/kg per day dose had been receiving parenteral support for 3.7 years and received 4.5 L/day parenteral support at baseline."

Looking at safety, although no "clinically meaningful differences" were observed through the study period in terms of patient vital signs, electrocardiograms, body weight, and physical examinations, the authors did report that 50 of the 52 patients reported at least one treatment-emergent adverse event, most commonly headache (35%), nausea (31%), or abdominal pain (25%).

The authors conceded that while they assume that reductions in PN requirements would translate to improvements in quality of life, the study was not sufficiently powered to address that question.

"It remains to be seen what the overall applicability of this product will be in clinical practice," they added.

The study was sponsored by NPS Pharmaceuticals, maker of teduglutide. Dr. O’Keefe and all his coauthors disclosed financial ties to NPS.

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