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Neurogastroenterol Motil. 2014 Mar;26(3):326-33. doi: 10.1111/nmo.12264. Epub 2013 Dec 30.

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

Author information

1
Division of Gastroenterology & Hepatology, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA.

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.

KEYWORDS:

IBS-C; abdominal pain; clinical response; complete spontaneous bowel movement; guanylate cyclase type-C receptor

PMID:
24382134
PMCID:
PMC4282394
DOI:
10.1111/nmo.12264
[Indexed for MEDLINE]
Free PMC Article

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