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Objective:To explore the value of linaclotide combined with compound polyethylene glycol electrolytes powder (PEG) for bowel preparation for colonoscopy.Methods:A randomized and single blind prospective clinical study was conducted in patients who intended to receive colonoscopy at the Department of Gastroenterology in Shenzhen Hospital, Southern Medical University from June 2021 to August 2021. One hundred and fifty-two patients in the experimental group were treated with 580 μg linaclotide + 2 L PEG, and 152 patients in the control group were treated with 3 L PEG. The bowel preparation effects including Boston bowel preparation scale (BBPS) score, bubble score and lesion detection rate, and safety (adverse events) were compared between the two groups.Results:The total BBPS scores were 9 (8, 9) in the experimental group, and 9 (9, 9) in the control group with no significant difference ( Z=0.141, P=0.888). The bubble scores were 1 (1, 2) in the experimental group, and 1 (1, 1) in the control group with no significant difference ( Z=1.788, P=0.074). There was no significant difference in detection rate of lesions between the experimental group and the control group [37.50% (57/152) VS 33.55% (51/152), χ2=0.517, P=0.472]. There was no significant difference in safety including incidence of nausea [7.24% (11/152) VS 13.16% (20/152), χ2=2.910, P=0.088], vomiting [2.63% (4/152) VS 7.24% (11/152), χ2=3.436, P=0.064], abdominal distension [7.89% (12/152) VS 11.84% (18/152), χ2=1.331, P=0.249] and abdominal pain [2.63% (4/152) VS 4.61% (7/152), χ2=0.849, P=0.357] between the experimental group and the control group. Conclusion:Linaclotide combined with PEG for colonoscopic bowel preparation reduces drinking water volume. The cleaning effect and safety are comparable to using 3 L PEG. It can be recommended for bowel preparation for colonoscopy.
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OBJECTIVE To comprehensively evaluate the effectiveness， safety and economics of linaclotide in the treatment of constipated irritable bowel syndrome （IBS-C）， and to provide the evidence-based basis for clinical application. METHODS Rapid health technology assessment method was adopted； PubMed， Embase， the Cochrane Library， Web of Science， CNKI， Wanfang data， VIP database， SinoMed， and related HTA websites were searched. Systematic review/meta-analysis， HTA reports and pharmacoeconomic research about linaclotide were collected. After literature screening， data extraction and quality evaluation， descriptive analysis was used to classify and summarize the research results. RESULTS A total of 11 literature were included， involving 7 systematic reviews/meta-analyses and 4 pharmacoeconomic research. In terms of effectiveness， compared with placebo， linaclotide could achieve FDA specified endpoint and European Medicines Agency-recommended endpoint faster， significantly improved patients’ complete spontaneous bowel movements （CSBM）， abdominal pain， constipation and quality of life， and relieved patients’ global symptoms； compared with the indirect evidence of lubiprostone， plecanatide and tenapanor， the efficacy of linaclotide at the FDA specified endpoint， CSBM， abdominal pain relief， and global relief response were the best. In terms of safety， the incidence of overall adverse drug reactions， diarrhea and flatulence caused by linaclotide were significantly higher than placebo，but patients can tolerate them. In terms of economics， compared with traditional therapeutic drugs， linaclotide showed an economic advantage. CONCLUSIONS Linaclotide has advantages in efficacy， safety and economics in the treatment of IBS-C. It is an effective strategy for the treatment of IBS-C.
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Background: The traditional bowel preparation compound polyethylene glycol electrolyte powder (PEG) has poor tolerance in some patients due to the need for a large amount of water, which has a limited cleaning effect and affects the visual field of observation. Therefore, it is of clinical significance to find a bowel cleaning method with strong cleaning power, high safety and is acceptable to most of the patients. Aims: To explore the efficacy and safety of PEG combined with linaclotide in bowel preparation. Methods: A total of 414 patients were randomly divided into 3 groups: control group (3 L PEG group), observation group A (3 L PEG+290 μg linaclotide), observation group B (2 L PEG+290 μg linaclotide). The primary outcome was the efficacy of bowel preparation based on the Boston bowel preparation scale (BBPS), the secondary outcomes were withdrawal time, time interval from preparation to colonoscopy, incidence of complications, cecal insertion rate, detection rates of polyps, adenoma, hemorrhoid and other diseases. BBPS score in constipation subgroup was analyzed. Results: The appropriate bowel preparation rate, BBPS score, and detection rates of polyps and hemorrhoid in observation group A were significantly higher than those in control group and observation group B (P0.05). There were no significant differences in cecal insertion rate, incomplete colonoscopy rate, detection rates of adenoma and other diseases, withdrawal time, time interval from preparation to colonoscopy, and incidence of adverse reactions among the three groups (P>0.05). BBPS score in constipation patients in observation group A was significantly higher than that in observation group B and control group (P<0.05). Conclusions: Linaclotide is safe and effective as an adjuvant for bowel preparation. 3 L PEG combined with linaclotide can improve the quality of bowel cleaning.
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Objective:To evaluate the efficacy and safety of linaclotide with polyethylene glycol in bowel preparation.Methods:From September 2021 to February 2022, 240 patients who visited the Department of Gastroenterology, Third People′s Hospital of Hubei Province, Jianghan University and underwent colonoscopy were selected. According to the random number table, in the ratio of 1 to 1, the patients were divided into the linaclotide with polyethylene glycol group and the simple polyethylene glycol group, with 120 cases in each group. The patients in the linaclotide with polyethylene glycol group took 580 μg linaclotide and 2 L polyethylene glycol electrolyte powder solution, and the patients in the simple polyethylene glycol group took 3 L polyethylene glycol electrolyte powder solution. The Boston bowel preparation scale(BBPS) score, the detection rate of polyps or adenomas, the insertion time of colonoscopy, the withdrawal time of colonoscopy, the time of the first defecation, the frequency of defecations, the success rate of cecal intubation, the occurrence of adverse effects and the satisfaction rate of patients were compared between the 2 groups. Independent sample t test and chi-square test were used for statistical analysis. Results:A total of 235 patients completed bowel preparation and accepted colonoscopy. There were no statistically significant differences in the BBPS score, the detection rate of polyps or adenomas, the insertion time of colonoscopy, the withdrawal time of colonoscopy, the success rate of cecal intubation and the frequency of defecations between the linaclotide with polyethylene glycol group and simple polyethylene glycol group(7.3±1.1 vs. 7.0±1.2; 58.1%, 68/117 vs. 60.2%, 71/118; 38.5%, 45/117 vs. 39.8%, 47/118; (4.2±1.9) min vs.(4.3±1.6) min; (5.9±2.7) min vs.(6.2±2.4) min; 100.0%, 117/117 vs. 100.0%, 118/118; 5.3±2.3 vs. 5.1±2.7; all P>0.05). The rate of adverse effects of the linaclotide with polyethylene glycol group was lower than that of simple polyethylene glycol group(25.6%, 30/117 vs. 39.8%, 47/118), the satisfaction rate of patients was higher than that of the simple polyethylene glycol group (93.2%, 109/117 vs. 76.3%, 90/118), and the differences were statistically significant( χ2=0.24 and 0.64, P=0.018 and 0.031). Conclusion:Compared with the 3 L polyethylene glycol regimen, 580 g linaclotide with 2 L polyethylene glycol regimen can achieve the same bowel preparation effect with higher safety and patient satisfaction, which is worthy of clinical application.
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Linaclotide is the first secretagogue approved for the treatment of irritable bowel syndrome with constipation in China. A group of experts in digestive diseases was convened to discuss the clinical use of linaclotide in China on June 26, 2021. Experts concluded at the seminar that the clinical efficacy of linaclotide should be comprehensively evaluated based on the improvement of constipation and abdominal symptoms; the clinicians should emphasize the importance to patient satisfaction; and the administration time, dose and duration of linaclotide treatment can be optimized according to the treatment response, lifestyle, severity of symptoms and drug sensitivity. In addition, the experts believed that communication with patients should be strengthened to help them to establish reasonable expectations to the efficacy and optimize the treatment regimen timely according to their feedback.
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Background: Irritable bowel syndrome with constipation (IBS-C) is a common functional gastrointestinal disorder. The current commonly used therapeutic drugs are not quite effective. Linaclotide is the globally first guanylate cyclase-C agonist, and provides a new selection for the treatment of IBS-C. Aims: To systematically evaluate the efficacy and safety of linaclotide in treatment of patients with IBS-C. Methods: Randomized controlled trials (RCTs) of linaclotide in the treatment of IBS-C were retrieved from CNKI, Wanfang Database, China VIP Database, PubMed, Embase, Cochrane Library. Literatures were independently screened by three reviewers, data were extracted and quality of the included studies was evaluated. The meta-analysis of efficacy of linaclotide on abdominal pain, complete spontaneous bowel movements (CSBM), spontaneous bowel movements (SBM)≤ 24 hours after first dose, adequate relief of IBS-C symptoms, constipation severity, IBS severity, and incidence of adverse reactions were conducted. Results: A total of six RCTs meeting the requirements were retrieved. Linaclotide could improve abdominal pain (RR=1.49, 95% CI: 1.15-1.92), CSBM (RR=3.03, 95% CI: 2.41-3.82), SBM≤ 24 hours after first dose (RR=1.60, 95% CI: 1.49-1.72), adequate relief of IBS-C symptoms (RR=1.63, 95% CI: 1.27-2.10), constipation severity (RR=1.45, 95% CI: 1.34-1.57), IBS severity (RR=1.44, 95% CI: 1.32-1.57). The incidences of diarrhea and bloat were significantly increased in linaclotide group than in placebo group, however, tolerance of the adverse reactions was well. Conclusions: Linaclotide has good efficacy, safety and tolerance in the treatment of IBS-C, and is a comparatively ideal drug for treatment of IBS-C.
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Objective To use hemin as a catalyst in the formation of disulfide bonds in the synthesis of linaclotide. Methods The linaclotide peptide was synthesized by the standard 9-fluorenylmethyl(Fmoc)solid-phase synthetic strategy. Wang resin and Trt-protected cysteine were used in the synthesis. Hemin was used in random oxidation of line linaclotide. The result was compared with those of air,dimethyl sulfoxide(DMSO),and I2 oxidation systems. Results and Conclusion Hemin is a highly effective catalyst for disulfide bond formation in linaclotide synthesis. It overcomes some disadvantages in oxidation reactions with conventional oxidative re-agents,and supplies a convenient way for the synthesis of peptide with concentrated disulfide bonds.
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Chronic constipation is one of the most common digestive diseases frequently observed in a clinical setting. It has been known to cause considerable damage to the quality of life of patients. Despite recent developments, there are considerable limitations in the use of constipation-modulating agents in Korea. Chloride channel inhibitors, such as lubiprostone and linaclotide, have not been introduced in Korea yet, and prucalopride and several kinds of polyethylene glycol are not covered under medical insurance. This article assesses medicines that are clinically available for the management of constipation in Korea, with a brief review of agents that have recently developed around the world.
Subject(s)
Humans , Chloride Channels , Constipation , Drug Therapy , Insurance , Korea , Lubiprostone , Polyethylene Glycols , Quality of LifeABSTRACT
The treatment of constipation aims to regulate the frequency and quantity of stool in order to promote successful defecation. Numerous studies on pharmacologic treatments and non-pharmacologic therapies for constipation have attempted to overcome limitations such as temporary and insufficient efficacy. Conventional laxatives have less adverse effects and are inexpensive, but often have limited efficacy. Recently developed enterokinetic agents and intestinal secretagogues have received attention owing to their high efficacies and low incidences of adverse events. Studies on biofeedback and surgical treatment have focused on improving symptoms as well as quality of life for patients with refractory constipation.
Subject(s)
Humans , Biofeedback, Psychology , Constipation , Defecation , Incidence , Laxatives , Quality of LifeABSTRACT
A significant proportion of chronic constipation patients are dissatisfied with their treatment. Recently, a number of new medications have been introduced for patients refractory to conventional laxatives, such as prucalopride, lubiprostone, linaclotide, and elobixibat. Prucalopride is a novel gastrointestinal prokinetic agent that acts as a 5-hydroxytryptamine type 4 (5-HT4) agonist. Compared with older nonselective 5-HT4 agonists, the higher selectivity of prucalopride for 5-HT4 receptors can reduce the risk of significant adverse cardiovascular events. Prucalopride improves stool frequency and consistency, and reduces the need for rescue medications. Lubiprostone, a chloride channel activator, increases the secretion of intestinal fluid, improves the stool frequency and consistency, and reduces straining. Linaclotide, a guanylate cyclase-C agonist, is effective in treating patients with chronic constipation and its effect on visceral sensitivity, as shown mainly in animal studies, provides an attractive pharmaceutical option for patients with irritable bowel syndrome with constipation. Elobixibat is an ileal sodium-dependent bile acid transporter inhibitor that blocks the enterohepatic circulation of bile acids, increasing the bile acid concentration in the intestine, which accelerates colonic transit and softens the stool. A phase III trial of the treatment of chronic constipation and irritable bowel syndrome with constipation is underway. The clinical application of new-generation laxatives will contribute to the management of chronic constipation refractory to conventional laxatives.
Subject(s)
Animals , Humans , Bile , Bile Acids and Salts , Chloride Channels , Colon , Constipation , Enterohepatic Circulation , Intestines , Irritable Bowel Syndrome , Laxatives , Receptors, Serotonin, 5-HT4 , Serotonin , Serotonin 5-HT4 Receptor Agonists , LubiprostoneABSTRACT
Chronic constipation is a very common clinical problem with its prevalence of up to 14% in the general population. It is not a life-threatening disease, but since patient's satisfaction to the treatment is known to be as low as 50%, chronic constipation still remains a clinically challenging problem. Fortunately, many new treatments have been introduced or are to be introduced in the near future. This article will review the basic concepts and the results of recent studies on the new treatments for chronic constipation.
Subject(s)
Humans , Chloride Channel Agonists/therapeutic use , Chronic Disease , Constipation/drug therapy , Laxatives/therapeutic use , Polyethylene Glycols/therapeutic use , Prevalence , Probiotics/therapeutic use , Serotonin 5-HT4 Receptor Agonists/therapeutic useABSTRACT
Linaclotide, a 14 aminoacid peptide is an intestinal secretagogue and works by stimulating guanylate cyclase (GC-C) present in the intestinal epithelium, which leads to improvement in symptoms of irritable bowel syndrome with constipation and chronic constipation in adults. Treatments available currently for these gastrointestinal problems have not been very satisfactory and many new options are therefore being explored to provide relief to these patients. Linaclotide has shown promising results in various clinical trials and hence was approved by US Food and Drug Administration (FDA) in 2012.