Efficacy, safety, and pharmacokinetics of teduglutide in adult Japanese patients with short bowel syndrome and intestinal failure: two phase III studies with an extension

Abstract

Purpose The short- and long-term efficacy, safety, and pharmacokinetics of teduglutide were analyzed in adult Japanese patients with short bowel syndrome and intestinal failure (SBS-IF). Methods Patients received teduglutide 0.05 mg/kg/day in clinical trials (TED-C14-004, SHP633-306, and extension SHP633-307). Data were analyzed at 24 weeks and an interim data cut-off of 4.5 years. Results The parenteral support (PS) volume decreased by ≥ 20% for 9/18 patients at 24 weeks and in all 11 patients by data cut-off in SHP633-307. The mean (standard deviation) PS volume decreased from baseline at 24 weeks in TED-C14-004 (−30.1 ± 25.9%) and SHP633-306 (−25.6 ± 25.5%), and at data cut-off in SHP633-307 (−57.08 ± 28.49%). Teduglutide was absorbed quickly. The adverse events were consistent with the underlying disease and known adverse drug reactions. Anti-teduglutide antibody titers declined with long-term treatment. Conclusions In Japanese adults with SBS-IF, teduglutide treatment was associated with clinically meaningful reductions in PS requirements, similar to findings in prior international studies. No new safety concerns specific to the Japanese SBS-IF patient population were identified with short- or long-term teduglutide treatment. Anti-teduglutide antibody titers disappeared in most Japanese adults with long-term treatment. These results constitute the longest evaluation of teduglutide treatment within clinical trials reported to date.

The indications and results of the use of teduglutide in patients with short bowel

“…Similar results were observed in a very recent Japanese study with the longest evaluation period ever reported (4.5 years), suggesting that, in the absence of rapid clinical response, TED should not be stopped early because it probably takes an average of over 2 years to achieve the peak physiologic effect [15]. In available studies, complete enteral autonomy was achieved in only 14-29% of patients [14][15][16][17][18][19] while a significant reduction in PS was seen in 62-93% of patients [14,20]. The amount of PS reduction is variable among different studies and seems to increase with time as mentioned above.…”

“…Furthermore, some slow responders may show a delayed response to TED with a decrease in PS volume after 6-26 months of treatment initiation, with 93% of patients having a significant response at 2 years of treatment [14]. Similar results were observed in a very recent Japanese study with the longest evaluation period ever reported (4.5 years), suggesting that, in the absence of rapid clinical response, TED should not be stopped early because it probably takes an average of over 2 years to achieve the peak physiologic effect [15]. In available studies, complete enteral autonomy was achieved in only 14-29% of patients [14][15][16][17][18][19] while a significant reduction in PS was seen in 62-93% of patients [14,20].…”