Does the oral adsorbent AST‐120 really improve symptoms for non‐constipating irritable bowel syndrome? authors’ reply

Abstract

SIRS, We read with interest the letter by Drs Flood and Donnellan on our study with AST-120 for the treatment of irritable bowel syndrome (IBS) symptoms. 2 We agree that the extension phases of the study may be prone to some bias. We want to clarify that the single-blind active phase was mainly included to increase patients’ willingness to participate in the trial, through a guaranteed phase of active treatment for some period of the trial. The single-blind, placebo phase was included to document loss of response when the drug was withdrawn. This methodology has been employed in many IBS trials. The analysis focused on the initial 8-week double-blind placebocontrolled phase, which is devoid of such biases. In their letter, Drs Flood and Donnellan ask about the basis for the sample size calculation. This was based on a single-center cross-over trial with citalopram in IBS, which used the same questionnaires as the present study. A final comment is made on the apparent loss of efficacy over placebo in the second half of the double-blind randomized phase of the trial. We think this effect is mainly due to a rise in placebo response, which may reflect the type of patients that entered the trial who were perhaps more prone to spontaneous improvement, as well as the relatively small sample size, and treatment expectations of the patients. This was an early-phase trial to evaluate the potential of AST-120, in doses that had previously been used for other indications, to improve IBS symptoms. In our view, the study demonstrated this potential for therapeutic benefit. It is clear that the current study is a preamble to more definitive, larger-scale studies with optimised design, inclusion criteria and evaluation parameters. Hence, any calculation of number-needed-to treat is premature, and requires the comprehensive data sets of later phase studies with AST-120.