@article {CheyA197, author = {W Chey and B Lavins and S Shiff and J MacDougall and C Kurtz and M Currie and J Johnston}, title = {PWE-166 Is Response To Linaclotide After 4 Weeks Of Treatment Predictive Of 12-week Improvement?}, volume = {63}, number = {Suppl 1}, pages = {A197--A198}, year = {2014}, doi = {10.1136/gutjnl-2014-307263.426}, publisher = {BMJ Publishing Group}, abstract = {Introduction Linaclotide is a minimally absorbed guanylate cyclase C agonist approved in the US and EU for irritable bowel syndrome with constipation (IBS-C). A question for prescribing physicians is whether to continue linaclotide in patients who do not improve during the early weeks of therapy. This post-hoc analysis assessed if response to linaclotide at Week 4 predicts Week 12 improvement, and if linaclotide should be continued in IBS-C patients not responding by Week 4. Methods Pooled data from 2 Phase 3 IBS-C trials of linaclotide were analysed. For Degree of Relief of IBS Symptoms, Degree of Relief of Abdominal Pain, and Spontaneous Bowel Movement [SBM] frequency, a patient{\textquoteright}s Week-4 clinical response was used to predict improvement at Week 12. For the purposes of determining a patient{\textquoteright}s Week-4 response, the 7-point balanced Degree of Relief scale was collapsed into 3 categories: Improved (completely, considerably, or somewhat relieved), Unchanged, and Worse (somewhat worse, considerably worse, or as bad as I can imagine) compared with baseline. For SBM frequency, a dichotomous end point was used: SBMs increased by >=2/week or not increased by >=2/week from baseline. Results The proportion of patients who had response at Week 4 was significantly greater for linaclotide- vs placebo-treated patients: 72 vs. 47\% for Degree of Relief of IBS Symptoms, 70 vs. 47\% for Degree of Relief of Abdominal Pain, and 59\% vs 33\% for SBM frequency (all comparisons: p \< 0.0001). For all parameters, most linaclotide-treated patients (>=70\%) who had response at Week 4 were improved at Week 12. For linaclotide-treated patients whose symptoms were unchanged at Week 4 for Degree of Relief of IBS Symptoms and Degree of Relief of Abdominal Pain, 36 and 39\% were improved at Week 12, vs. 19 and 21\% of the placebo group, respectively (p \< 0.05). For SBM frequency, 30\% of linaclotide-treated patients vs. 17\% of placebo-treated patients without response at Week 4 were improved (SBMs >=2) at Week 12 (p \< 0.05). Conclusion Patients whose IBS symptoms improved after 4 weeks with linaclotide were likely to maintain improvement. At least 30\% of linaclotide patients who were unchanged at Week 4 experienced symptom improvement by Week 12. The significant differences between linaclotide and placebo in the percentage of patients improved at Week 12 who were unchanged at Week 4 indicates that in some patients >=1 month of linaclotide therapy may be required for improvement. Hence, an initial course of linaclotide therapy in patients with IBS-C shou.ld be \>4 weeks. Study funded by Forest Laboratories, Inc., and Ironwood Pharmaceuticals, Inc. Disclosure of Interest W. Chey Consultant for: Ironwood Pharmaceuticals, Forest Research Institute, B. Lavins Shareholder of: Ironwood Pharmaceuticals, Employee of: Ironwood Pharmaceuticals, S. Shiff Shareholder of: Forest Research Institute, Employee of: Forest Research Institute, J. MacDougall Shareholder of: Ironwood Pharmaceuticals, Employee of: Ironwood Pharmaceuticals, C. Kurtz Shareholder of: Ironwood Pharmaceuticals, Employee of: Ironwood Pharmaceuticals, M. Currie Shareholder of: Ironwood Pharmaceuticals, Employee of: Ironwood Pharmaceuticals, J. Johnston Shareholder of: Ironwood Pharmaceuticals, Employee of: Ironwood Pharmaceuticals.}, issn = {0017-5749}, URL = {https://gut.bmj.com/content/63/Suppl_1/A197.2}, eprint = {https://gut.bmj.com/content/63/Suppl_1/A197.2.full.pdf}, journal = {Gut} }