The placebo response rate in pharmacological trials in patients with irritable bowel syndrome: a systematic review and meta-analysis

Bosman, Michelle; Elsenbruch, Sigrid; Corsetti, Maura; Tack, Jan; Simrén, Magnus; Winkens, Björn; Boumans, Thimo; Masclee, Ad; Keszthelyi, Dániel

doi:10.1016/s2468-1253(21)00023-6

Cited by 40 publications

(39 citation statements)

References 117 publications

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Section: Discussionmentioning

confidence: 99%

“…Response rates to placebo are known to be high among randomized clinical trials conducted in IBS patients 25 . This might be attributed to various factors, such as patients' expectations of drug efficacy, variations in their psychiatric states and the definition of end‐points (where an improvement threshold of 30% for abdominal pain/discomfort might permit a high placebo response rate) 25,26 . Yet the observed placebo response was considerably greater in the Chinese sub‐cohort compared with the previous North American trials, especially for the 12‐week abdominal pain/discomfort end‐point.…”

Section: Discussionmentioning

confidence: 99%

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Efficacy and safety of linaclotide in patients with irritable bowel syndrome with constipation: Chinese sub‐cohort analysis of a phase III, randomized, double‐blind, placebo‐controlled trial

Peng

Fang

Dai

et al. 2022

J of Digest Diseases

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Objective To conduct a sub‐cohort analysis to evaluate the efficacy and safety of linaclotide in Chinese patients with constipation‐predominant irritable bowel syndrome (IBS‐C) using data from a completed trial (NCT01880424). Methods In this phase III, double‐blind, placebo‐controlled trial, IBS‐C patients were randomized to receive linaclotide (290 μg/d) or placebo for 12 weeks. Efficacy was assessed with two co‐primary responder end‐points (12‐wk abdominal pain/discomfort: ≥30% reduction in either score with neither deteriorating from baseline for ≥6 wks; 12‐wk IBS degree of relief: score ≤2 for ≥ 6 wks), seven secondary endpoints and several additional end‐points. Results In total, 659 Chinese IBS‐C patients received linaclotide (n = 327) or placebo (n = 332). The 12‐week abdominal pain/discomfort end‐point was met in 62.1% and 53.3% of the linaclotide‐treated and placebo‐treated patients, respectively (odds ratio [OR] 1.43, 95% confidence interval [CI] 1.05‐1.96, P = 0.023); the 12‐week IBS degree of relief end‐point was achieved in 32.7% and 16.9% of the patients treated with linaclotide and placebo, respectively (OR 2.40, 95% CI 1.66‐3.47, P < 0.001). The linaclotide‐treated patients had a shorter time to the first spontaneous bowel movement than the placebo‐treated patients (23.6 h vs 43.7 h, P < 0.001). Linaclotide produced significantly greater improvement than placebo in all secondary end‐points from the first 2 weeks (all P < 0.001). Diarrhea was reported in 8.3% of linaclotide‐treated patients and 1.2% of placebo‐treated patients. Conclusion Linaclotide (290 μg/d) was efficacious and well‐tolerated in Chinese IBS‐C patients with a rapid onset of effect.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of linaclotide in patients with irritable bowel syndrome with constipation: Chinese sub‐cohort analysis of a phase III, randomized, double‐blind, placebo‐controlled trial

Peng

Fang

Dai

et al. 2022

J of Digest Diseases

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“…The placebo effect is well-studied and documented in many populations, and may be particularly pronounced for pharmacological trials in IBS. 37,38 Placebo effects cannot be excluded as the cause of any treatment effects seen in these duloxetine studies. There were also other specific methodological concerns identified, including Kaplan et al's exclusion of "placebo-responders" after a 2-week placebo run-in phase prior to open-label treatment phase.…”

Section: Ta B L E 4 (Continued)mentioning

confidence: 96%

Oral and parenteral anti‐neuropathic agents for the management of pain and discomfort in irritable bowel syndrome: A systematic review and meta‐analysis

Lambarth

Zárate-López

Fayaz

2021

Neurogastroenterology Motil

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Background: Irritable bowel syndrome (IBS) is a highly prevalent and economically burdensome condition; and pain is often the most unpleasant, disruptive, and difficultto-treat symptom. Visceral hypersensitivity is a common feature driving pain in IBS, suggesting that neuropathic mechanisms may be implicated. We conducted a systematic review of available evidence to examine the role of anti-neuropathic medicines in the management of pain in IBS. Methods:We systematically searched scientific repositories for trials investigating conventional oral, and/or parenteral, pharmaceutical antineuropathic treatments in patients with IBS. We summarized key participant characteristics, outcomes related to pain (primary outcome), and selected secondary outcomes. Key results:We included 13 studies (n = 629 participants): six investigated amitriptyline, three duloxetine, three pregabalin, and one gabapentin. There was considerable methodological and statistical heterogeneity, so we performed a narrative synthesis and limited meta-analysis. Amitriptyline was most extensively studied, though only in diarrhea-predominant patients. In individual trials, amitriptyline, pregabalin and gabapentin generally appeared beneficial for pain outcomes. While duloxetine studies tended to report improvements in pain, all were un-controlled trials with high risk of bias. Meta-analysis of three studies (n = 278) yielded a pooled relative-risk of 0.50 (95%CI 0.38-0.66) for not improving with anti-neuropathic agent vs control. We did not identify any eligible studies investigating the role of parenteral anti-neuropathics. Conclusions and inferences:Anti-neuropathic analgesics may improve pain in IBS, and deserve further, high-quality investigation, potentially considering parenteral administration and agents with minimal gastrointestinal motility effects. Investigation of amitriptyline's efficacy in non-diarrhea-predominant subtypes is currently lacking, and we recommend particular caution for its use in IBS-C.

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“…The lack of interest of the pharmaceutical industry is also a problem. Pharmaceutical firms are probably discouraged because the heterogeneity of the IBS has made previous pharmacological interventions of limited therapeutic efficacy, resulting in therapeutic gains of only 8%–14% in responder rates compared to placebo in several large trials 14 …”

Section: Neurogastroenterology: the Forgotten Discipline?mentioning

confidence: 99%

How to raise the interest for neurogastroenterology among young gastroenterologists?

2021

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The placebo response rate in pharmacological trials in patients with irritable bowel syndrome: a systematic review and meta-analysis

Cited by 40 publications

References 117 publications

Efficacy and safety of linaclotide in patients with irritable bowel syndrome with constipation: Chinese sub‐cohort analysis of a phase III, randomized, double‐blind, placebo‐controlled trial

Efficacy and safety of linaclotide in patients with irritable bowel syndrome with constipation: Chinese sub‐cohort analysis of a phase III, randomized, double‐blind, placebo‐controlled trial

Oral and parenteral anti‐neuropathic agents for the management of pain and discomfort in irritable bowel syndrome: A systematic review and meta‐analysis

How to raise the interest for neurogastroenterology among young gastroenterologists?

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