P2473 - Linaclotide Improves Symptoms of Irritable Bowel Syndrome With Constipation, Irrespective of Severity and Age: A Post-Hoc Analysis of Pooled Trials

Tuesday, October 26, 2021

10:30 AM – 4:00 PM PT

Location: Shoreline Exhibit Hall

Has Audio

Presenting Author(s)

Lin Chang, MD, FACG

David Geffen School of Medicine at UCLA
Los Angeles, CA, United States

Lin Chang, MD, FACG¹, Lesley A. Houghton, PhD, FACG², Alexander C. Ford, MD³, Wilmin Bartolini, PhD⁴, James Wu, PhD⁴, Elizabeth P. Shea, PhD⁴, Wieslaw Bochenek, MD⁵, Ramesh Boinpally, PhD⁶, Cristina Almansa, MD, PhD⁴
¹David Geffen School of Medicine at UCLA, Los Angeles, CA; ²Leeds Institute of Medical Research at St. James’s, the University of Leeds, Leeds, England, United Kingdom; ³University of Leeds School of Medicine, Leeds, England, United Kingdom; ⁴Ironwood Pharmaceuticals, Inc., Boston, MA; ⁵Former employee of AbbVie Inc., Madison, NJ; ⁶AbbVie Inc., Madison, NJ

Introduction: Linaclotide (LIN) is a guanylate cyclase-C agonist approved for treating irritable bowel syndrome with constipation (IBS-C) and is efficacious for improving abdominal symptoms. Studies have reported age- or sex-related effects on IBS symptom severity,^1,2 which may impact the efficacy of IBS treatments. This study aimed to assess: (1) whether IBS-C abdominal symptom severity varies with age and (2) whether potential age-related differences impact the efficacy of LIN.

Methods: Data were pooled from one Phase 2b and three Phase 3 randomized controlled trials of LIN 290 µg vs. placebo (PBO) in IBS-C (2009–2019; NCT00460811, NCT00948818, NCT00938717, NCT03573908). Inclusion criteria were similar across studies; patients met Rome II or III criteria for IBS-C and had baseline abdominal symptom severity scores ≥3 (0–10 scale; 10= very severe / worst possible). Baseline scores and percentage change from baseline after treatment were analyzed by age group: 18–29, 30–39, 40–49, 50–59, and ≥60 years.

Results: Of 2292 patients included, 87% were female. Overall, baseline abdominal symptom severity scores appeared higher in the mid-age (30–60 years) vs. youngest and oldest groups (Table). Confidence intervals suggested statistical differences in baseline abdominal discomfort and bloating scores between some age groups. Abdominal discomfort was more severe in the 50–59 vs. ≥60 years group and bloating was more severe in the 50–59 vs. both ≥60 and 18–29 years groups. An analysis of baseline symptom severity with age as a continuous variable suggested severity peaked ~50 years. Percentage change from baseline for abdominal pain, discomfort, and bloating showed improvements in severity for LIN vs. PBO in most age groups. These changes included greater improvement in the mid-age groups, which had higher baseline severity scores (Figure).

Discussion: In this cohort of mostly females with IBS-C, we report baseline age-related differences in IBS-C abdominal symptom severity (discomfort and bloating; less so for pain). We identified an intriguing peak symptom severity in the 50–59 years group which should be explored further, particularly given research linking symptom severity with hormonal changes.² Importantly, LIN was effective across most age groups analyzed for improving abdominal symptoms, regardless of baseline symptom severity.

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Tang YR et al. World J Gastroenterol. 2012;18(48):7175–7183.

Editorial assistance by Complete HealthVizion.

Figure: Figure. Percentage change (± standard error) in abdominal symptom severity at Week 12 by age group. For linaclotide 290 µg vs. placebo: *p<0.001; **p<0.005; ***p<0.05.

	Age groups (N=2292)
	18–29 years (n=374)	30–39 years (n=436)	40–49 years (n=651)	50–59 years (n=496)	≥60 years (n=335)
Females, n (%)	319 (85.3)	396 (90.8)	583 (89.6)	447 (90.1)	254 (75.8)
Baseline severity scores, mean (95% CI)
Abdominal pain	5.8 (5.61, 5.93)	6.0 (5.80, 6.12)	5.9 (5.74, 6.00)	6.0 (5.84, 6.15)	5.7 (5.46, 5.85)
Abdominal discomfort	6.1 (5.99, 6.29)	6.3 (6.16, 6.47)	6.3 (6.13, 6.38)	6.4^a (6.29, 6.57)	6.0 (5.84, 6.22)
Abdominal bloating	6.5 (6.32, 6.65)	6.8^a^,^b (6.66, 6.98)	6.7^a (6.58, 6.84)	6.9^a,b (6.72, 7.03)	6.4 (6.18, 6.56)

Point estimates for any two age groups were considered statistically different if their CIs did not overlap. Shaded boxes: ^aSignificantly different vs. ≥60 years group; ^bSignificantly different vs. 18–29 years group.
CI, confidence interval.

Table: Table. Baseline abdominal symptom severity by age group.

Disclosures:

Lin Chang: Ironwood Pharmaceuticals, Inc. – Advisory Committee/Board Member.

Lesley Houghton: Ironwood Pharmaceuticals, Inc. – Advisory Committee/Board Member.

Alexander Ford: Ironwood Pharmaceuticals, Inc. – Advisory Committee/Board Member.

Wilmin Bartolini: Ironwood Pharmaceuticals, Inc. – Employee, Stockholder/Ownership Interest (excluding diversified mutual funds).

James Wu: Ironwood Pharmaceuticals, Inc. – Employee, Stockholder/Ownership Interest (excluding diversified mutual funds).

Elizabeth Shea: Ironwood Pharmaceuticals, Inc. – Employee, Stockholder/Ownership Interest (excluding diversified mutual funds).

Wieslaw Bochenek: AbbVie Inc. – Stockholder/Ownership Interest (excluding diversified mutual funds), Other Financial or Material Support, Former employee.

Ramesh Boinpally: AbbVie Inc. – Employee, Stockholder/Ownership Interest (excluding diversified mutual funds).

Cristina Almansa: Ironwood Pharmaceuticals, Inc. – Employee, Stockholder/Ownership Interest (excluding diversified mutual funds).

Lin Chang, MD, FACG¹, Lesley A. Houghton, PhD, FACG², Alexander C. Ford, MD³, Wilmin Bartolini, PhD⁴, James Wu, PhD⁴, Elizabeth P. Shea, PhD⁴, Wieslaw Bochenek, MD⁵, Ramesh Boinpally, PhD⁶, Cristina Almansa, MD, PhD⁴. P2473 - Linaclotide Improves Symptoms of Irritable Bowel Syndrome With Constipation, Irrespective of Severity and Age: A Post-Hoc Analysis of Pooled Trials, ACG 2021 Annual Scientific Meeting Abstracts. Las Vegas, Nevada: American College of Gastroenterology.