Responders vs clinical response: a critical analysis of data from linaclotide phase 3 clinical trials in IBS-C.

Abstract

BACKGROUND:

US Food and Drug Administration (FDA) set a rigorous standard for defining patient responders in irritable bowel syndrome-C (IBS-C; i.e., FDA's Responder Endpoint) for regulatory approval. However, this endpoint's utility for health-care practitioners to assess clinical response has not been determined. We analyzed pooled IBS-C linaclotide trial data to evaluate clinically significant responses in linaclotide-treated patients who did not meet the FDA responder definition.

METHODS:

Percentages of FDA non-responders reporting improvement in abdominal pain, bowel function and/or global relief measures were determined using pooled data from two linaclotide Phase 3 IBS-C trials.

KEY RESULTS:

1602 IBS-C patients enrolled; 34% of linaclotide-treated and 17% of placebo-treated patients met the FDA Responder Endpoint (p < 0.0001). Among FDA non-responders at week 12, 63% of linaclotide-treated patients reported their abdominal pain was at least somewhat relieved, compared with 48% of placebo-treated patients. For stool frequency, 62% of linaclotide-treated patients reported that they were at least somewhat improved at week 12, compared with 46% of placebo-treated patients. For global IBS symptoms, 65% of linaclotide-treated patients reported at least some IBS-symptom relief, 43% reported adequate relief of IBS symptoms, and 57% reported being satisfied with linaclotide treatment, vs placebo rates of 48%, 34%, and 41% respectively.

CONCLUSIONS & INFERENCES:

Most linaclotide-treated IBS-C patients who were FDA non-responders reported some improvement in abdominal pain and stool frequency, and global relief/satisfaction. In addition to the FDA Responder Endpoint, differing response thresholds and symptom-specific change from baseline should be considered by clinicians for a complete understanding of clinical response to linaclotide and other IBS-C therapies.

• Authors: B E Lacy, A J Lembo, J E Macdougall, S J Shiff, C B Kurtz, M G Currie, J M Johnston
• Journal: Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society (Neurogastroenterol Motil) Vol. 26 Issue 3 Pg. 326-33 (Mar 2014) ISSN: 1365-2982 [Electronic] England
• PMID: 24382134 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2013 Ironwood Pharmaceuticals. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.

Chemical References

• Peptides
• linaclotide

Topics

• Abdominal Pain (drug therapy)
• Adult
• Aged
• Aged, 80 and over
• Clinical Trials, Phase III as Topic
• Female
• Humans
• Irritable Bowel Syndrome (drug therapy)
• Male
• Middle Aged
• Peptides (therapeutic use)
• Treatment Outcome
• Young Adult