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Responders vs clinical response: a critical analysis of data from linaclotide phase 3 clinical trials in IBS-C.
Neurogastroenterol Motil 2014; 26(3):326-33NM

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+Show Affiliations

Division of Gastroenterology & Hepatology, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24382134

Citation

Lacy, B E., et al. "Responders Vs Clinical Response: a Critical Analysis of Data From Linaclotide Phase 3 Clinical Trials in IBS-C." Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society, vol. 26, no. 3, 2014, pp. 326-33.
Lacy BE, Lembo AJ, Macdougall JE, et al. Responders vs clinical response: a critical analysis of data from linaclotide phase 3 clinical trials in IBS-C. Neurogastroenterol Motil. 2014;26(3):326-33.
Lacy, B. E., Lembo, A. J., Macdougall, J. E., Shiff, S. J., Kurtz, C. B., Currie, M. G., & Johnston, J. M. (2014). Responders vs clinical response: a critical analysis of data from linaclotide phase 3 clinical trials in IBS-C. Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society, 26(3), pp. 326-33. doi:10.1111/nmo.12264.
Lacy BE, et al. Responders Vs Clinical Response: a Critical Analysis of Data From Linaclotide Phase 3 Clinical Trials in IBS-C. Neurogastroenterol Motil. 2014;26(3):326-33. PubMed PMID: 24382134.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Responders vs clinical response: a critical analysis of data from linaclotide phase 3 clinical trials in IBS-C. AU - Lacy,B E, AU - Lembo,A J, AU - Macdougall,J E, AU - Shiff,S J, AU - Kurtz,C B, AU - Currie,M G, AU - Johnston,J M, Y1 - 2013/12/30/ PY - 2013/07/11/received PY - 2013/10/29/accepted PY - 2014/1/3/entrez PY - 2014/1/3/pubmed PY - 2014/10/17/medline KW - IBS-C KW - abdominal pain KW - clinical response KW - complete spontaneous bowel movement KW - guanylate cyclase type-C receptor SP - 326 EP - 33 JF - Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society JO - Neurogastroenterol. Motil. VL - 26 IS - 3 N2 - 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. SN - 1365-2982 UR - https://www.unboundmedicine.com/medline/citation/24382134/Responders_vs_clinical_response:_a_critical_analysis_of_data_from_linaclotide_phase_3_clinical_trials_in_IBS_C_ L2 - https://doi.org/10.1111/nmo.12264 DB - PRIME DP - Unbound Medicine ER -