Efficacy and safety of linaclotide in treatment-resistant chronic constipation: A multicenter, open-label study.

Takeo Kurihashi, Yusuke Tanaka, Tomohiro Takatsu, Tsutomu Yoshihara, Keiichi Ashikari, Akiko Fuyuki, Takuma Higurashi, Takaomi Kessoku, Noboru Misawa, Hidenori Ohkubo, Koji Yamamoto, Michihiro Iwaki, Atsushi Nakajima, Machiko Nakatogawa, Izuru Terada, Masataka Morita

Journal: Neurogastroenterology and motility 2024;36(12):e14938

PMID: 39370607

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Abstract

BACKGROUND

This study aimed to evaluate the efficacy and safety of linaclotide in patients with chronic constipation (CC) or irritable bowel syndrome with constipation (IBS-C) who did not respond to treatment with magnesium oxide (MgO).

METHODS

This study was designed as a multicenter, open-label, single-arm, exploratory study. Patients with CC or IBS-C who took MgO and those meeting the medication initiation criteria were administered linaclotide at a daily dosage of 500 μg for 12 weeks. The primary endpoint was a change in the Japanese version of the Patient Assessment of Constipation Quality of Life (JPAC-QOL) score from baseline, which was evaluated by using a paired t-test.

KEY RESULTS

The patients' mean age (± standard deviation) was 67.6 ± 13.82 years. The full analysis set included 61 patients. The JPAC-QOL total score was 1.60 at baseline and 0.70 at 12 weeks, with a significant mean change of -0.89 ± 0.721 (p < 0.001). Several secondary endpoints also showed improvement. The frequency of spontaneous bowel movement (SBM) and complete SBM increased by 2.70 ± 7.254 (p < 0.01) and 2.81 ± 5.254 times, respectively (p < 0.001). The Bristol Stool Form Scale, abdominal bloating severity, and straining severity scores improved by 1.33 ± 1.274 (p < 0.001), -0.16 ± 0.563 (p < 0.05), and -0.46 ± 0.795 (p < 0.001) points, respectively. The safety analysis set included 65 patients, 7 of whom had diarrhea, which improved with dose reduction and drug withdrawal.

CONCLUSION & INFERENCES

The study was conducted in an older adult population, similar to real clinical practice. Linaclotide may be an option for treating CC that shows an inadequate response to conventional therapy.

Address: Department of Gastroenterology and Hepatology, Yokohama City University School of Medicine, Yokohama, Kanagawa, Japan.; Department of Internal Medicine, Kanagawa Dental University Yokohama Clinic, Yokohama, Kanagawa, Japan.; Department of Internal Medicine, NamikiKoiso-medical Clinic, Yokohama, Kanagawa, Japan.; Department of Gastroenterology and Hepatology, Yokohama City University School of Medicine, Yokohama, Kanagawa, Japan.; Department of Internal Medicine, Kanagawa Dental University Yokohama Clinic, Yokohama, Kanagawa, Japan.; Department of Internal Medicine, NamikiKoiso-medical Clinic, Yokohama, Kanagawa, Japan.; Department of Palliative Medicine, Yokohama City University Hospital, Yokohama, Kanagawa, Japan.; Department of Palliative Medicine, International University of Health and Welfare Narita Hospital, Narita, Chiba, Japan.; Department of Gastroenterology, International University of Health and Welfare Graduate School of Medicine, Narita, Chiba, Japan.; Department of Gastroenterology and Hepatology, Yokohama City University School of Medicine, Yokohama, Kanagawa, Japan.; Department of Gastroenterology and Hepatology, Yokohama City University School of Medicine, Yokohama, Kanagawa, Japan.; Department of Palliative Medicine, Yokohama City University Hospital, Yokohama, Kanagawa, Japan.; Department of Gastroenterology and Hepatology, Yokohama City University School of Medicine, Yokohama, Kanagawa, Japan.; Department of Internal Medicine, Kanagawa Dental University Yokohama Clinic, Yokohama, Kanagawa, Japan.; Department of Palliative Medicine, Yokohama City University Hospital, Yokohama, Kanagawa, Japan.; Department of Internal Medicine, Kanagawa Dental University Yokohama Clinic, Yokohama, Kanagawa, Japan.; Department of Primary Care and General Medicine, Tokyo Medical University, Tokyo, Japan.; Department of Internal Medicine, NamikiKoiso-medical Clinic, Yokohama, Kanagawa, Japan.; Department of Data Science, Yokohama City University School of Medicine, Yokohama, Kanagawa, Japan.; Operational Excellence, Medical Affairs, Astellas Pharma Inc., Tokyo, Japan.; Data Science, Astellas Pharma Inc., Tokyo, Japan.; Medical Specialty, Medical Affairs, Astellas Pharma Inc., Tokyo, Japan.

DOI: 10.1111/nmo.14938

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MeSH Terms: Humans, Constipation, Male, Female, Middle Aged, Peptides, Aged, Treatment Outcome, Chronic Disease, Quality of Life, Guanylyl Cyclase C Agonists, Aged, 80 and over, Irritable Bowel Syndrome, Adult, Gastrointestinal Agents