Treatment Of Chronic Idiopathic Constipation Research Articles

Efficacy and safety of linaclotide in treating functional constipation in paediatric patients: a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial

Linaclotide, a guanylate cyclase C agonist, has been approved in the USA for the treatment of chronic idiopathic constipation and irritable bowel syndrome with predominant constipation in adults. We aimed to assess the efficacy and safety of linaclotide in paediatric patients aged 6-17 years with functional constipation. This randomised, double-blind, placebo-controlled, multicentre, phase 3 study was done at 64 clinic or hospital sites in seven countries (USA, Canada, Israel, Italy, the Netherlands, Ukraine, and Estonia). Patients aged 6-17 years who met modified Rome III criteria for functional constipation were randomly assigned (1:1), with a block size of four and stratified by age (6-11 years and 12-17 years), to receive either oral linaclotide 72 μg or placebo once daily for 12 weeks. Participants, investigators, and data assessors were masked to assignment. The primary efficacy endpoint was change from baseline (CFB) in the 12-week frequency rate of spontaneous bowel movements (SBMs; occurring in the absence of rescue medication on the calendar day of or before the bowel movement) per week and the secondary efficacy endpoint was CFB in stool consistency over the 12-week treatment period; efficacy and safety were analysed in all patients in the randomised population who received at least one dose of study intervention (modified intention-to-treat population and safety population, respectively). The study is registered with ClinicalTrials.gov, NCT04026113, and the functional constipation part of the study is complete. Between Oct 1, 2019, and March 21, 2022, 330 patients were enrolled and randomly assigned to linaclotide (n=166) or placebo (n=164). Two patients in the linaclotide group did not receive any treatment; thus, efficacy and safety endpoints were assessed in 328 patients (164 patients in each group). 293 (89%) patients completed the 12-week treatment period (148 in the linaclotide group and 145 in the placebo group). 181 (55%) of 328 patients were female and 147 (45%) were male. At baseline, the mean frequency rate for SBMs was 1·28 SBMs per week (SD 0·87) for placebo and 1·16 SBMs per week (0·83) for linaclotide, increasing to 2·29 SBMs per week (1·99) for placebo and 3·41 SBMs per week (2·76) for linaclotide during intervention. Compared with placebo (least-squares mean [LSM] CFB 1·05 SBMs per week [SE 0·19]), patients treated with linaclotide showed significant improvement in SBM frequency (LSM CFB 2·22 SBMs per week [0·19]; LSM CFB difference 1·17 SBMs per week [95% CI 0·65-1·69]; p<0·0001). Linaclotide also significantly improved stool consistency over placebo (LSM CFB 1·11 [SE 0·08] vs 0·69 [0·08]; LSM CFB difference 0·42 [95% CI 0·21-0·64]; p=0·0001). The most reported treatment-emergent adverse event (TEAE) by patients treated with linaclotide was diarrhoea (seven [4%] of 164 vs three [2%] of 164 patients in the placebo group) and by patients treated with placebo was COVID-19 (five [3%] vs four [2%] in the linaclotide group). The most frequent treatment-related TEAE was diarrhoea (linaclotide: six [4%] patients; placebo: two [1%] patients). One serious adverse event of special interest (treatment-related severe diarrhoea resulting in dehydration and hospitalisation) occurred in a female patient aged 17 years in the linaclotide group; this case resolved without sequelae after administration of intravenous fluids. No deaths occurred during the study. Linaclotide is an efficacious and well tolerated treatment for functional constipation in paediatric patients and has subsequently been approved by the US Food and Drug Administration for this indication. AbbVie and Ironwood Pharmaceuticals.

Efficacy and safety of vibrating capsule in treatment of chronic idiopathic constipation: a systematic review and meta-analysis of randomized controlled trials.

Multiple pharmacological interventions and modalities are available for managing chronic idiopathic constipation (CIC), with variable efficacy. Vibrating capsule (VC) is a device that has shown variable results in alleviating constipation by tactile stimulation of the colonic wall and inducing peristalsis. This meta-analysis is to investigate the efficacy and safety of this modality. Comprehensive literature search was performed through June 14th, 2023, on databases including Embase, PubMed/MEDLINE, Cochrane Central, Web of Science, Global Index Medicus, and Google Scholar. Core concepts of VC, constipation, and bowel movement were searched. The DerSimonian-Laird method and random effects model were utilized. We calculated odds ratio (OR) and mean difference (MD) for proportional and continuous variables, respectively, with 95% confidence interval (CI) and a P value of <0.05 considered statistically significant. The search strategy yielded 117 articles. Four studies with 705 total patients were finalized comparing VC to placebo/sham treatment. The pooled complete spontaneous bowel movement (CSBM), defined as bowel movement without use of laxatives within the last 48 hours with sense of complete evacuation did not achieve statistical improvement with VC (MD =0.153; 95% CI: -0.218 to 0.523; P=0.422). However, spontaneous bowel movement (SBM), defined as bowel movement without use of laxatives within the last 48 hours, showed statistical improvement with VC (MD =0.159; 95% CI: 0.095 to 0.223; P<0.001). VC didn't show an increase in pooled adverse events (OR =1.431; 95% CI: 0.702 to 2.916; P=0.324). The systematic review and meta-analysis suggest that VC is safe and efficacious in some outcomes, however, larger randomized controlled trials (RCTs) and real-world data are needed to establish this.

Linaclotide (Linzess) for functional constipation.

The guanylate cyclase-C receptor agonist linaclotide (Linzess – Abbvie/Ironwood) was first approved by the FDA in 2012 for treatment of chronic idiopathic constipation and irritable bowel syndrome with constipation in adults.

Laxative effect of prebiotics in chronic constipation: Mechanisms of action

Constipation is a condition that affects a consistent part of the general population, with increasing numbers of incidence worldwide. Its causes can be attributed to several factors. One of these factors (and one of the most relevant causes) is dietary choices. For instance, poor nutrition habits have been shown to adversely affect the function of the digestive tract, eliciting abnormal physiological responses that might lead to constipation. Prebiotics are specialized types of fermentable fibres which have been hypothesised to play a beneficial role in the treatment of chronic idiopathic constipation. Fructo-oligosaccharides (FOS), galacto-oligosaccharides (GOS) and inulin are the most common types of prebiotics. There are several studies to demonstrate that prebiotics have many interactions with the bowel and its movements, thus they are potentially beneficial in the treatment of chronic idiopathic constipation. Some prebiotics can retain water and therefore increase stool mass and viscosity, making the passage of faeces through the gastrointestinal tract easier. In addition, prebiotics can feed the probiotic bacteria (the body’s “good” bacteria that synergistically live in the digestive tract), and the fermentation of prebiotics by the probiotic bacteria leads to the production of short-chain fatty acids (SCFAs). SCFA synthesis through prebiotic fermentation has been shown to improve gastrointestinal function and bowel movement. Moreover, prebiotic fermentation in the colon might trigger both immunomodulatory responses and the production of neurotransmitters that elicit stronger contractility in the colon. Prebiotic fermentation from the gut microbiota might trigger the release of neurotransmitters that interact with the central nervous system (CNS) and enteric nervous system (ENS). These bacterial neuromodulators directly affect the digestive nerve terminals, eliciting responses from the digestive tract that result in a faster and easier defaecation. Besides the existing studies that describe the roles of prebiotics in gut health and motility, their beneficial role has not yet been fully understood and proven, thus further research is needed on the topic.

A Patient-Centered Approach to Managing IBS-C and CIC.

At the end of the activity, participants will be able to: Implement a staged strategy for the diagnostic evaluation of irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation (CIC) based on history and physical examination, including the Rome IV criteria. Discuss the evidence and guideline recommendations for self-care as well as over-the-counter (OTC) and prescription therapies to treat IBS-C and CIC, Individualize treatment for IBS-C and CIC emphasizing patient-centered care to address patient concerns, improve outcomes, and enhance quality of life.

Plecanatide for the treatment of chronic idiopathic constipation and irritable bowel syndrome with constipation: Post hoc analyses of placebo-controlled trials in adults with severe constipation.

Patients with chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (IBS-C) often experience severe symptoms. The current aim was to evaluate plecanatide in adults with CIC or IBS-C with severe constipation. Data were analyzed post hoc from randomized, placebo-controlled trials (CIC [n = 2], IBS-C [n = 2]) of plecanatide 3 mg, 6 mg, or placebo administered for 12 weeks. Severe constipation was defined as no complete spontaneous bowel movements (CSBMs) and an average straining score ≥3.0 (CIC; 5-point scale) or ≥8.0 (IBS-C; 11-point scale) during a 2-week screening. Primary efficacy endpoints were durable overall CSBM responders (CIC: ≥3 CSBMs/week, plus increase from baseline of ≥1 CSBM/week, for ≥9 of 12 weeks, including ≥3 of the last 4 weeks) and overall responders (IBS-C: ≥30% reduction from baseline in abdominal pain and ≥1 CSBM/week increase for ≥6 of 12 weeks). Severe constipation was observed in 24.5% (646/2639) and 24.2% (527/2176) of CIC and IBS-C populations, respectively. The CIC durable overall CSBM response rate (plecanatide 3 mg, 20.9%; plecanatide 6 mg, 20.2%; placebo, 11.3%) and IBS-C overall response rate (plecanatide 3 mg, 33.0%; plecanatide 6 mg, 31.0%; placebo, 19.0%) were significantly greater with plecanatide versus placebo (p ≤ 0.01 for all). Median time to first CSBM in CIC and IBS-C populations were significantly shorter with plecanatide 3 mg versus placebo (p = 0.01 for both). Plecanatide was effective in the treatment of severe constipation in adults with CIC or IBS-C.

Efficacy and safety of lubiprostone for the treatment of chronic idiopathic constipation: A phase 3, randomized, placebo-controlled study

IntroductionChronic idiopathic constipation (CIC) negatively impacts quality of life and increases healthcare costs. Lubiprostone stimulates the secretion of intestinal fluid, in turn facilitating the passage of stools and alleviating associated symptoms. Lubiprostone has been available in Mexico since 2018, but its clinical efficacy has not been studied in a Mexican population. AimTo evaluate the efficacy of lubiprostone, assessed by changes in spontaneous bowel movement (SBM) frequency after one week of treatment with 24 μg oral lubiprostone (b.i.d.), as well as its safety, over four weeks of treatment. StudyRandomized, double-blind, placebo-controlled study on 211 adults with CIC in Mexico. ResultsThe increase in SBM frequency, after one week of treatment, was significantly higher in the lubiprostone group than in the placebo group (mean: 4.9 [SD: 4.45] vs. 3.0 [3.14], p = 0.020). Secondary efficacy endpoints revealed a significantly higher proportion of SBM frequency/week in the lubiprostone group at weeks 2, 3, and 4. There was a better response within 24 h after the first dose with lubiprostone vs. placebo (60.0% vs. 41.5%; OR: 2.08, CI95%: [1.19, 3.62], p = 0.009) and the lubiprostone group also had significant improvement, with respect to straining, stool consistency, abdominal bloating, and Satisfaction Index. The main adverse events were gastrointestinal disorders in 13 (12.4%) lubiprostone-treated subjects and 4 (3.8%) control subjects. ConclusionsOur data confirm the efficacy and safety of lubiprostone for the treatment of CIC in a Mexican population. Lubiprostone treatment induces relief from the most bothersome symptoms associated with constipation.

American Gastroenterological Association-American College of Gastroenterology Clinical Practice Guideline: Pharmacological Management of Chronic Idiopathic Constipation.

Chronic idiopathic constipation (CIC) is a common disorder associated with significant impairment in quality of life. This clinical practice guideline, jointly developed by the American Gastroenterological Association and the American College of Gastroenterology, aims to inform clinicians and patients by providing evidence-based practice recommendations for the pharmacological treatment of CIC in adults. The American Gastroenterological Association and the American College of Gastroenterology formed a multidisciplinary guideline panel that conducted systematic reviews of the following agents: fiber, osmotic laxatives (polyethylene glycol, magnesium oxide, lactulose), stimulant laxatives (bisacodyl, sodium picosulfate, senna), secretagogues (lubiprostone, linaclotide, plecanatide), and serotonin type 4 agonist (prucalopride). The panel prioritized clinical questions and outcomes and used the Grading of Recommendations Assessment, Development, and Evaluation framework to assess the certainty of evidence for each intervention. The Evidence to Decision framework was used to develop clinical recommendations based on the balance between the desirable and undesirable effects, patient values, costs, and health equity considerations. The panel agreed on 10 recommendations for the pharmacological management of CIC in adults. Based on available evidence, the panel made strong recommendations for the use of polyethylene glycol, sodium picosulfate, linaclotide, plecanatide, and prucalopride for CIC in adults. Conditional recommendations were made for the use of fiber, lactulose, senna, magnesium oxide, and lubiprostone. This document provides a comprehensive outline of the various over-the-counter and prescription pharmacological agents available for the treatment of CIC. The guidelines are meant to provide a framework for approaching the management of CIC; clinical providers should engage in shared decision making based on patient preferences as well as medication cost and availability. Limitations and gaps in the evidence are highlighted to help guide future research opportunities and enhance the care of patients with chronic constipation.

Effects of treatment cessation and re-treatment in randomized controlled trials of prucalopride in patients with chronic idiopathic constipation.

Prucalopride is a selective, high-affinity serotonin type 4 receptor agonist approved for the treatment of chronic idiopathic constipation (CIC) in adults. We investigated the impact of prucalopride cessation and re-treatment on efficacy and safety. Data were from two randomized controlled trials in adults with CIC. In a dose-finding trial, complete spontaneous bowel movements (CSBMs) and treatment-emergent adverse events (TEAEs) were assessed during a 4-week run-out period after a 4-week treatment period (TP; prucalopride 0.5-4 mg once daily or placebo). In a re-treatment trial, CSBMs and TEAEs were assessed during two 4-week TPs (prucalopride 4 mg once daily or placebo) separated by a 2- or 4-week washout period. In the dose-finding trial (N=234; 43-48 patients/group), mean CSBMs/week and the proportion of responders (≥3 CSBMs/week) were higher with prucalopride than placebo during the TP, but similar in all groups 1-4 weeks after treatment cessation. TEAEs were less frequent following treatment cessation. In the re-treatment trial (efficacy analyses: prucalopride, n=189; placebo, n=205), the proportion of responders was similar in both TPs and significantly higher (p ≤ 0.001) with prucalopride (TP1, 38.6%; TP2, 36.0%) than placebo (TP1, 10.7%; TP2, 11.2%). Most patients who responded to prucalopride in TP1 responded again in TP2 (71.2%). TEAEs were less frequent in TP2 than TP1. Prucalopride cessation resulted in a loss of clinical effect to baseline levels within 7 days. Similar efficacy and safety were observed between TP1 and TP2 after prucalopride was re-initiated following a washout period.

Tissue distribution and abuse potential of prucalopride: findings from non-clinical and clinical studies.

Prucalopride is a selective serotonin type 4 (5-HT4) receptor agonist indicated for treatment of chronic idiopathic constipation (CIC) in adults (2 mg orally, daily). 5-HT4 receptors are present in the central nervous system; therefore, non-clinical and clinical assessments were performed to evaluate the tissue distribution and abuse potential of prucalopride. In vitro receptor-ligand binding studies were performed to assess the affinity of prucalopride (≤1 mM) for peptide receptors, ion channels, monoamine neurotransmitters and 5-HT receptors. The tissue distribution of 14C-prucalopride (5 mg base-equivalent/kg) was investigated in rats. Behavioural assessments in mice, rats and dogs after treatment with single or repeated (up to 24 months) subcutaneous or oral doses of prucalopride (0.02-640 mg/kg across species) were performed. Treatment-emergent adverse events possibly indicative of abuse potential during prucalopride CIC clinical trials were evaluated. Prucalopride showed no appreciable affinity for the receptors and ion channels investigated; its affinity (at ≤100 μM) for other 5-HT receptors was 150-10,000 times lower than that for the 5-HT4 receptor. In rats, <0.1% of the administered dose was found in the brain and concentrations were below the limit of detection within 24 hours. At supratherapeutic doses (≥20 mg/kg), mice and rats exhibited palpebral ptosis, and dogs exhibited salivation, eyelid tremors, decubitis, pedalling movements and sedation. All clinical treatment-emergent adverse events, possibly indicative of abuse potential, except dizziness, occurred in <1% of patients treated with prucalopride or placebo. This series of non-clinical and clinical studies suggest low abuse potential for prucalopride.

Exploring Pharmacological Treatments for Chronic Idiopathic Constipation in Adults: A Look Back to the Future

Despite great progress in pharmaceutical research, the medical treatment of chronic idiopathic constipation is far from ideal. The aim of the present article was to review literature data, focusing on poorly studied or commercially unavailable/unapproved drugs potentially useful for the treatment of chronic idiopathic constipation in adults. An extensive online literature search was conducted using the keywords "chronic constipation", "colon", "constipation", "drugs", "laxatives", and "treatment", in various combinations between January 1960 and December 2022. The literature search showed the presence of some drugs whose efficacy has only recently been demonstrated by modern investigations, and which are likely to be incorporated into future guidelines, of others that are proven effective and potentially effective on constipated patients but limited by small or relatively old studies, or by side effects which could be used in experienced hands, and of others that might be useful but lack a solid scientific background. Looking into the future for patients with chronic constipation might add some more tools to the therapeutic portfolio, especially for certain subgroups of these patients.

S523 A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy, Safety and Tolerability of ANJ908, a Novel DGAT1 Inhibitor, in Patients With Chronic Idiopathic Constipation

Introduction: Current treatment for chronic idiopathic constipation (CIC) is limited by: 1. Low magnitude of drug effect (increase of only ∼1-1.5 SBM per week) 2. Low overall response rate (typically < 20%) 3. Loss of efficacy within 3-6 months. Real-world experience where CIC patients often cycle through 2-4 pharmacotherapies shows the need for new medications with better efficacy. ANJ908 is a safe and well-tolerated diacylglycerol acyltransferase (DGAT) 1 inhibitor which increases bowel movement number and softens the stool in humans. We designed and conducted a phase 2 study of ANJ908 in CIC patients and present the data here for the first time. Methods: ANJ908C2102 was a multicenter, randomized, placebo-controlled, double-blind study designed to assess the efficacy and safety of ANJ908 in CIC patients. Patients meeting ROME IV diagnostic criteria for functional constipation (a.k.a. CIC) and had < 3 SBMs/week for prior the two weeks were eligible. Enrolled patients underwent a 2 week run-in period where all previous constipation treatment was stopped. After run-in, patients were randomized (1:1:1) to 4 weeks of once daily treatment with placebo, ANJ908 at 20 or 40 mg. Bowel movement timing, stool details, and patient reported constipation symptoms were recorded in an eDiary. Patient safety labs and AEs were monitored throughout the study. Results: A total of 191 patients were randomized. Patients were 77.9% female, with a mean (SD) age and BMI of 42.2 (14.4) years and 23.2 (4.36) kg/m2, respectively. ANJ908 increased the mean (SE) placebo-subtracted number of SBM/week by +2.28 (0.75; p = 0.0027) and +3.10 (0.74; p < 0.0001) and CSBM/week by +1.53 (0.70; p = 0.03) and +1.81 (0.70; p = 0.01), respectively at week 4. ANJ908 improved stool consistency, provided constipation relief, decreased straining severity, and reduced rescue medication use. ANJ908 was safe and generally well tolerated. Mild diarrhea, nausea and vomiting were the most common AEs with a total of 7 (out of 64) patients in the ANJ908 20 mg group discontinuing treatment due to AEs. Conclusion: ANJ908 demonstrated increases in weekly SBMs and CSBMs to a magnitude greater than previous treatments. Furthermore, ANJ908 improved patient reported stool consistency and relief of constipation symptoms. The benefit-risk profile of ANJ908 justifies advancement into phase 3 clinical development to confirm its efficacy and safety. If this profile is confirmed, ANJ908 may become a treatment better able to address the unmet need in CIC patients.

S556 Potential of Tenapanor as a Treatment for Chronic Idiopathic Constipation (CIC): A Post Hoc Analysis From the T3MPO-1 and T3MPO-2 Phase 3 Studies for Irritable Bowel Syndrome With Constipation (IBS-C) in Adults

S556 Potential of Tenapanor as a Treatment for Chronic Idiopathic Constipation (CIC): A Post Hoc Analysis From the T3MPO-1 and T3MPO-2 Phase 3 Studies for Irritable Bowel Syndrome With Constipation (IBS-C) in Adults

Polyethylene Glycol 3350 in the Treatment of Chronic Idiopathic Constipation: Post hoc Analysis Using FDA Endpoints

Methods This multicenter, double-blind, placebo-controlled, parallel-group trial included adults with chronic idiopathic constipation randomized to polyethylene glycol 3350 17 g (n = 204) or placebo (n = 100) once daily for 24 weeks. Post hoc analyses were performed using the US Food and Drug Administration endpoint (≥3 complete spontaneous bowel movements/week and an increase of ≥1 complete spontaneous bowel movement/week from baseline for ≥9/12 weeks, including 3 of the last 4 weeks) along with additional efficacy and safety outcomes. Results The proportion of patients meeting the new endpoint was significantly higher with polyethylene glycol 3350 vs placebo (42% vs 13%; P < 0.0001). Reductions in the mean number of hard/lumpy stools/week (–2.1 vs –0.9; P = 0.0014) and the weekly mean five-point cramping rating (–0.3 vs –0.1; P = 0.0272) also significantly favored polyethylene glycol 3350. The proportion of subjects with gastrointestinal adverse events decreased markedly after the first week of treatment in the polyethylene glycol 3350 group. Conclusion Using the current US Food and Drug Administration-recommended responder definition and other secondary outcomes, once-daily polyethylene glycol 3350 demonstrated substantial and sustained efficacy and safety over 24 weeks in patients with chronic idiopathic constipation. Trial Registration. The original trial was registered with https://clinicaltrials.gov Trial: NCT00153153.

Safety and Efficacy of Elobixibat, an Ileal Bile Acid Transporter Inhibitor, in Elderly Patients With Chronic Idiopathic Constipation According to Administration Time: Interim Analysis of Post-marketing Surveillance.

Background/AimsElobixibat, an ileal bile acid transporter (apical sodium-dependent bile acid transporter) inhibitor, was recently launched in Japan for the treatment of chronic idiopathic constipation. We conducted an interim analysis of post-marketing surveillance to evaluate the safety and efficacy of elobixibat in elderly patients with chronic constipation and compared the efficacy according to administration time.MethodsSafety and efficacy outcomes were evaluated through patient interviews for 4 weeks.ResultsAdverse drug reactions (ADRs) were observed in 5.24% of the 1049 patients analyzed; diarrhea (2.19%) and abdominal pain (1.81%) were the most common. A serious ADR of death was reported in one patient (0.10%). The incidence of ADRs in the ≥ 65-year old or ≥ 75-year-old subpopulation was similar to that in the total patient population. Mean bowel movements per week significantly increased from 2.9 ± 2.5 at baseline to 5.0 ± 3.1 (P < 0.001) at Week 2 and 5.3 ± 2.6 (P < 0.001) at Week 4. The mean Bristol Stool Form Scale score significantly increased from 2.3 ± 1.4 at baseline to 3.8 ± 1.3 (P < 0.001) at Week 2 and 3.9 ± 1.1 at Week 4 (P < 0.001). Bowel movements significantly increased in the elderly population and subpopulations receiving elobixibat before breakfast, lunch, or dinner. The median time to bowel movement was 5 hours.ConclusionThe results suggested that elobixibat was well-tolerated and efficacious in elderly patients with chronic constipation and can be administered before any meals.

Mechanisms of Action of Current Pharmacologic Options for the Treatment of Chronic Idiopathic Constipation and Irritable Bowel Syndrome With Constipation.

Multiple therapeutic agents are currently available for the treatment of chronic idiopathic constipation and irritable bowel syndrome with constipation. A better understanding of the mechanism of action of each treatment provides important insights into expected responses and is key to optimizing treatment outcomes. Some constipation treatments, such as stimulant laxatives, may increase bowel movement frequency but are ineffective at relieving, and may even exacerbate, abdominal symptoms. On the contrary, prescription treatments, such as the guanylyl cyclase-C agonists, for example, may improve bowel symptoms and reduce visceral hypersensitivity. This review summarizes the mechanisms of action of commonly used over-the-counter and prescription therapies for chronic idiopathic constipation and irritable bowel syndrome with constipation, outlining how these mechanisms contribute to the efficacy and safety of each treatment option.

DIAGNOSIS AND MANAGEMENT OF CHRONIC IDIOPATHIC CONSTIPATION: A NARRATIVE REVIEW FROM A BRAZILIAN EXPERT TASK FORCE.

Chronic idiopathic constipation (CIC) is a condition that widely affects the global population, represents relevant healthcare resource utilization and costs, and impacts the individual's well-being. To review the consensus of expert societies and published guidelines on the diagnosis and treatment of CIC in adults, seeking to assist reasoning and decision-making for medical management of patients with CIC and provide a practical reference material. A Brazilian medical task force searched the scientific literature in the following electronic databases: MEDLINE/PubMed, SciELO, EMBASE and Cochrane, using the following descriptors: chronic constipation, diagnosis, management of chronic constipation. In addition, a review of articles on the mechanism of action, safety, and efficacy of therapeutic options available in Brazil was carried out. The diagnostic approach and the understanding of the pathophysiology present in CIC are essential items to indicate the appropriate therapy and to understand the ecosystem of the patient's needs. CIC is a common condition in adults, occurring more frequently in the elderly and in women. Proper management is defined by detailed medical history and physical examination, together with appropriate therapeutics, regardless pharmacological or not, and depending on the best moment of indication. This way, the impact on quality of life is also optimized.

A Systematic Review and Network Meta-Analysis on the Efficacy of Medications in the Treatment of Chronic Idiopathic Constipation in Japan.

Background In the 2010s, medications with new mechanisms were introduced in Japan for the treatment of chronic idiopathic constipation (CIC). A few systematic reviews have compared medications' relative efficacy, but the reviews included studies on patients from various races, even though the mechanism of CIC is considered to differ between races. The aim of this study was to use a systematic review and network meta-analysis to compare the relative efficacy of these medications in Japanese patients. Methods We conducted a meta-analysis and report it here according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We identified studies by searching MEDLINE (via the PubMed interface) and the Cochrane Library and ICHUSHI databases and included randomized clinical trials that compared medications for CIC with placebo in Japanese adults. Two reviewers independently screened and assessed articles, abstracted data, and assessed the risk of bias. We pooled data by random-effects meta-analyses and also performed a Bayesian network meta-analysis to indirectly compare data. Results The present systematic review and meta-analyses included 1460 patients in 6 randomized clinical trials: 2 on linaclotide, 3 on elobixibat, 2 on lubiprostone, and 1 on lactulose. The results of direct comparisons showed that linaclotide, elobixibat, and lubiprostone were superior to placebo in the change of spontaneous bowel movements (SBMs) within 1 week: linaclotide, 1.95 (95% CI, 1.51-2.39); elobixibat, 5.69 (95% CI, 3.31-8.07); and lubiprostone, 2.41 (95% CI, 0.82-4.01). The Bayesian network meta-analysis showed consistent results. Elobixibat 10 mg was ranked first for the increase in SBMs and complete SBMs within 1 week and the time to first SBM. Lubiprostone 48 μg was ranked first for the proportion of patients with SBM within 24 hours. Conclusion Our direct and indirect meta-analyses revealed that the new CIC medications available in Japan have equal efficacy but that elobixibat and lubiprostone are highly likely to be more efficacious.

Effect of Rosa damascene Mill. Hydroalcoholic Extract on the Treatment of Chronic Idiopathic Constipation in Adults

Effect of Rosa damascene Mill. Hydroalcoholic Extract on the Treatment of Chronic Idiopathic Constipation in Adults

Efficacy of Senna and Magnesium Oxide for the Treatment of Chronic Idiopathic Constipation.

Efficacy of Senna and Magnesium Oxide for the Treatment of Chronic Idiopathic Constipation.