Responders vs clinical response: a critical analysis of data from linaclotide phase 3 clinical trials in IBS‐C. Issue 3 (30th December 2013)

• Record Type: Journal Article
• Authors: Lacy, B. E.; Lembo, A. J.; MacDougall, J. E.; Shiff, S. J.; Kurtz, C. B.; Currie, M. G.; Johnston, J. M.
• Is Part Of: Neurogastroenterology & motility. Volume 26:Issue 3(2014:Mar.)
• Page Start: 326
• Page End: 333
• Publication Date: 2013-12-30
• Subjects: Gastrointestinal system -- Motility -- Periodicals; Gastrointestinal system -- Innervation -- Periodicals; 616.33
• DOI: 10.1111/nmo.12264
• Languages: English
• ISSNs: 1350-1925

Abstract

<abstract abstract-type="main" id="nmo12264-abs-0001"> <title>Abstract</title> <sec id="nmo12264-sec-0001" sec-type="section"> <title>Background</title> <p>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.</p> </sec> <sec id="nmo12264-sec-0002" sec-type="section"> <title>Methods</title> <p>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.</p> </sec> <sec id="nmo12264-sec-0003" sec-type="section"> <title>Key Results</title> <p>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.</p> </sec> <sec id="nmo12264-sec-0004" sec-type="section"> <title>Conclusions & Inferences</title> <p>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.</p> </sec> </abstract>