Conclusions Sidney Cohen, MD Chairman, Department of Medicine Temple University School of Medicine Philadelphia, Pennsylvania Sidney Cohen, MD Chairman, Department of Medicine Temple University School of Medicine Philadelphia, Pennsylvania

CO 2 Irritable Bowel Syndrome (IBS)  Difficult to diagnose and treat  No measurable serologic or gastrointestinal motility marker of IBS  Diagnosis based on a compilation of symptoms  IBS treatment is empiric; no proven efficacious therapies for patients with abdominal pain, bloating, and constipation as their predominant symptoms  Difficult to diagnose and treat  No measurable serologic or gastrointestinal motility marker of IBS  Diagnosis based on a compilation of symptoms  IBS treatment is empiric; no proven efficacious therapies for patients with abdominal pain, bloating, and constipation as their predominant symptoms

CO 3 Tegaserod: Pharmacodynamic Effects  Tegaserod has a unique pharmacologic action that addresses the clinical components in IBS patients with abdominal pain, bloating, and constipation –Stimulates the peristaltic reflex, augmenting aboral propulsion –Diminishes visceral sensitivity, reducing pain  Tegaserod has a unique pharmacologic action that addresses the clinical components in IBS patients with abdominal pain, bloating, and constipation –Stimulates the peristaltic reflex, augmenting aboral propulsion –Diminishes visceral sensitivity, reducing pain

CO 4 Tegaserod Clinical Trials  Recruited a largely unrestricted population of patients with IBS who identified abdominal pain or discomfort and constipation as their predominant symptoms –Reflective of patients seen in common practice  Recruited a largely unrestricted population of patients with IBS who identified abdominal pain or discomfort and constipation as their predominant symptoms –Reflective of patients seen in common practice

CO 5 Tegaserod Clinical Effects: Symptoms of IBS Patients  Global relief of symptoms  Specific IBS symptoms –Abdominal discomfort and pain –Bloating –Constipation Stool frequency Stool consistency  Global relief of symptoms  Specific IBS symptoms –Abdominal discomfort and pain –Bloating –Constipation Stool frequency Stool consistency

CO 6 Effect on IBS Symptoms (B301) Placebo12 mg/d Pain score Bloating score *P <.05 versus placebo; † P <.01 versus placebo (change from baseline). * * * * * * * * † † † † † † † † † † † † † † * * * * † † † † * * * * † † † † † † † † † † * * * * * * † † † † † † † † † † † † † † † † † † † † † † † † † † † † † † † † † † † † † † Bowel movements Stool consistency

CO 7 Effect on IBS Symptoms (B351) Pain score Bloating score Bowel movements Stool consistency * * * * * * * * * * † † † † † † * * * * * * * * * * † † † † † † † † † † † † † † † † † † † † * * † † † † † † † † * * * * * * † † † † † † † † † † † † † † † † Placebo12 mg/d *P <.05 versus placebo; † P <.01 versus placebo (change from baseline). Significant: at least mild;  2 on a 6-point scale.

CO 8 Effect on IBS Symptoms (B307) Pain score Bloating score Bowel movements Stool consistency * * † † † † † † † † † † † † † † † † † † * * † † † † † † † † † † † † * * * * * * * * * * * * * * Placebo4-12 mg/d *P <.05 versus placebo; † P <.01 versus placebo (change from baseline). Significant: at least mild;  2 on a 6-point scale.

CO 9 Phase III Studies: Complete, Considerable, or Somewhat Relief B351 B301 B307 *P <.05 versus placebo. † P <.01 versus placebo. * * * * † † † * * * * * * † † * * † * † * *

CO 10 Phase III Studies Complete or Considerable Relief B351 B301 B307 *P <.05 versus placebo. † P <.01 versus placebo. * † * * * * † * * † † † † † † † †

CO 11 Summary  Tegaserod at a dose of 12 mg/d (6 mg BID) has been demonstrated to be effective in the treatment of abdominal pain, bloating, and constipation in IBS  Tegaserod is safe and well-tolerated –Diarrhea is the only drug-related side effect, which is self limiting and infrequently led to discontinuation  Tegaserod at a dose of 12 mg/d (6 mg BID) has been demonstrated to be effective in the treatment of abdominal pain, bloating, and constipation in IBS  Tegaserod is safe and well-tolerated –Diarrhea is the only drug-related side effect, which is self limiting and infrequently led to discontinuation

CO 12 Conclusion  Unique pharmacologic action that addresses the clinical components of constipation- predominant IBS –Enhances the peristaltic reflex and decreases visceral sensitivity  Positive and significant clinical effect in reducing abdominal pain, bloating, constipation and stool consistency, the hallmark symptoms of IBS  Effective in providing overall or global relief of the symptoms of IBS  Unique pharmacologic action that addresses the clinical components of constipation- predominant IBS –Enhances the peristaltic reflex and decreases visceral sensitivity  Positive and significant clinical effect in reducing abdominal pain, bloating, constipation and stool consistency, the hallmark symptoms of IBS  Effective in providing overall or global relief of the symptoms of IBS

CO 13 Bottom Line  In a clinical syndrome in which there has been no proven treatment, tegaserod is a strong first step in the management of constipation-predominant IBS