Northwestern University Feinberg School of Medicine Chicago, Illinois
Darren M. Brenner, MD, FACG1, Amol Sharma, MD, MS, FACG2, Reema Patel, PharmD3, Sarah Lorenzen, PhD4, Gregory S. Sayuk, MD, MPH5; 1Northwestern University Feinberg School of Medicine, Chicago, IL; 2Augusta University, Augusta, GA; 3Bausch Health US, LLC, Bridgewater Township, NJ; 4Salix Pharmaceuticals, Inc., Bridgewater Township, NJ; 5Washington University School of Medicine and John Cochran Veterans Affairs Medical Center, St. Louis, MO
Introduction: Abdominal bloating is a common and bothersome symptom of chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (IBS-C). CIC and IBS-C present as a spectrum of symptoms, including bloating. Clinicians recognize CIC and IBS-C patients with bloating as particularly challenging to treat, hence there is interest in examining treatment outcomes in patient populations with any bloating (CIC) and moderate to severe bloating severity (IBS-C) at baseline. Methods: Results from four phase 3 trials of plecanatide in CIC and IBS-C were analyzed. Eligible patients were randomized to placebo, plecanatide 3 mg, or plecanatide 6 mg for 12 weeks. Primary endpoints were consistent with current FDA-recommended guidance standards for CIC and IBS-C. Daily bloating scores were recorded electronically using the Likert Scale in CIC (0=none to 4=very severe) and a numeric rating scale in IBS-C (0=none to 10=worst possible). Patients with any bloating (CIC, ≥ 1) and moderate to severe baseline bloating (IBS-C, > 5) were evaluated. Results: At baseline 2270/2639 patients with CIC (86%) reported bloating and 1638/2176 patients with IBS-C (75%) met criteria for moderate to severe bloating. In this population, plecanatide-treated patients demonstrated significant improvements in primary efficacy endpoints compared to placebo (ie, percentage of CSBM responders in CIC and percentage of overall responders in IBS-C; Figure 1). Furthermore, significantly greater reductions in weekly mean abdominal bloating scores were identified in favor of plecanatide 3 mg and 6 mg compared to placebo in both the CIC and IBS-C cohorts (Figure 2) over the 12-week treatment period. Significant improvements in abdominal pain (least squares mean change from baseline CIC: 3 mg -0.58, 6 mg -0.57; IBS-C: 3 mg -1.66, 6 mg -1.75) were also reported across the 12 treatment weeks in patients with any bloating (CIC) and moderate to severe baseline bloating (IBS-C, Figure 3). Discussion: In patients with CIC with any baseline bloating and IBS-C with moderate to severe baseline bloating, both plecanatide doses (3 mg and 6 mg) yielded significant improvements in primary efficacy endpoints and reductions in abdominal bloating. Across 12 weeks, abdominal pain also significantly improved with plecanatide treatment.
Figure 1. Impact of plecanatide on (A) percentage of overall durable CSBM responders (CIC with any baseline bloating) and (B) overall responder rate (IBS-C with moderate to severe baseline bloating)
Figure 2. Change in abdominal bloating score in patients with (A) CIC with any baseline bloating and (B) IBS-C with moderate to severe baseline bloating
Figure 3. Change in abdominal pain score in patients with (A) CIC with any baseline bloating and (B) IBS-C with moderate to severe baseline bloating
Disclosures: Darren Brenner: IDP Foundation – Grant/Research Support. Salix Pharmaceuticals – Consultant, Speaker's Bureau. Amol Sharma: Ironwood Pharmaceuticals – Advisory Committee/Board Member. Salix Pharmaceuticals – Advisory Committee/Board Member. Reema Patel: Bausch Health – Employee, Stockholder/Ownership Interest (excluding diversified mutual funds). Sarah Lorenzen: Salix Pharmaceuticals – Employee. Gregory Sayuk: Allergan/Ironwood Pharmaceuticals – Consultant, Speaker's Bureau. GI Health Foundation – Consultant. Salix Pharmaceuticals – Consultant, Speaker's Bureau.