Efficacy of lubiprostone for functional constipation treatment in adolescents and children: Randomized controlled trial.

OBJECTIVES: Adolescent and pediatric functional constipation (FC) is a common clinical problem. Currently, data on lubiprostone for the treatment of pediatric FC are scarce. This study investigated the efficacy and safety of lubiprostone in the treatment of pediatric FC. METHODS: In a single-blinded, randomized controlled study, we included 280 patients aged 8-18 years with FC. Patients were randomized either to a weight-based lubiprostone dose (n = 140) or conventional laxatives (n = 140), including lactulose, bisacodyl, or sodium picosulfate, for 12 weeks, followed by 4 weeks posttreatment follow-up. RESULTS: Improvement in constipation was achieved in 128 (91.4%) patients in the lubiprostone group, and in 48 (34.3%) patients of the conventional therapy group (p < 0.001) and was sustained after treatment discontinuation. One quarter of the lubiprostone group experienced the first spontaneous bowel motion within 48 h after dose initiation. A total of 75.7% of the lubiprostone group could achieve and sustain Bristol stool form of 3 or 4 during the last 4 weeks of therapy and through the 4 weeks of follow-up versus 50 (35.7%) patients in the conventional therapy group (p < 0.001). No life-threatening adverse drug reactions were encountered, and no treatment-related discontinuation. Mild self-limited colicky abdominal pain and headache were the most prevalent side effects in the lubiprostone group. CONCLUSIONS: Lubiprostone is an effective and well-tolerated pharmacotherapy for youthful age and pediatric age groups, which may alter the paradigm of pediatric FC treatment.

Comparative profiles of lubiprostone, linaclotide, and elobixibat for chronic constipation: a systematic literature review with meta-analysis and number needed to treat/harm.

OBJECTIVE: To comprehensively evaluate the efficacy, safety, patient symptoms, and quality-of-life (QoL) of lubiprostone, linaclotide, and elobixibat as treatment for chronic constipation (CC). DESIGN: Systematic literature review (SLR) and meta-analysis (MA). Literature searches were conducted on PubMed and Embase using the Ovid platform. METHODS: SLR including randomized controlled trials (RCTs) and observational studies was conducted to identify the overall efficacy and safety of lubiprostone, linaclotide, and elobixibat. Thereafter, MA was performed using only RCTs. The number needed to treat (NNT) and number needed to harm (NNH) analyses were additionally conducted. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was efficacy regarding change in spontaneous bowel movements. Secondary outcomes included safety, constipation-related symptoms, and QoL. RESULTS: Twenty-four studies met the inclusion criteria for the SLR: 17 RCTs, 4 observational studies, and 3 single-arm trials. Feasibility assessment for the MA resulted in 14 studies available for safety data analysis, and 8 available for efficacy analysis, respectively. Three drugs showed similar efficacy in the MA and NNT analysis. However, the NNH analysis revealed distinct safety profiles: lubiprostone, linaclotide, and elobixibat were linked to the highest risk of nausea, diarrhea, and abdominal pain, respectively. CONCLUSION: The current study provides an updated overview of the efficacy, safety, patient symptoms, and QoL of the three drugs with different mechanisms of action for CC treatment.The findings could help physicians adopt an individualized approach for treating patients with CC in clinical practice.

Recommendations for the management of opioid-induced constipation - how to improve usability in clinical practice.

INTRODUCTION: Opioid-induced constipation remains undertreated despite effective and safe treatment options exists. Previous guidelines have only been partially effective in improving management, possibly due to their complexity, and studies suggest that a simple setup of concise and behaviorally-orientated steps improves usability. AREAS COVERED: This article introduces the concept of opioid-induced constipation and provides an overview of existing guidelines in this field. We also propose simplified recommendations for managing opioid-induced constipation, derived from a synthesis of current guidelines and the principles of optimal guideline design theory. EXPERT OPINION: Despite standard treatment with laxatives and fluid intake in patients with opioid-induced constipation, escalation of treatment is often needed where µ-opioid receptor antagonists or newer medications such as lubiprostone, linaclotide, or prucalopride are used. Previous guidelines have not been used sufficiently and thus management of the condition is often insufficient. We therefore propose simplified recommendations to management, which we believe can come into broader use. It was validated in primary care for credibility, clarity, relevance, usability, and overall benefit. We believe that this initiative can lead to better management of the substantial proportion of patients suffering from side effects of opioids.

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

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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.

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

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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.

AGA Clinical Practice Guideline on the Pharmacological Management of Irritable Bowel Syndrome With Constipation

Irritable bowel syndrome (IBS) is a common disorder of gut­brain interaction associated with significant disease burden. This American Gastroenterological Association guideline is intended to support practitioners in decisions about the use of medications for the pharmacological management of IBS-C and is an update of a prior technical review and guideline. The Grading of Recommendations Assessment, Development and Evaluation framework was used to assess evidence and make recommendations. The technical review panel prioritized clinical questions and outcomes according to their importance for clinicians and patients and conducted an evidence review of the following agents: tenapanor, plecanatide, linaclotide, tegaserod, lubiprostone, polyethylene glycol laxatives, tricyclic antidepressants, selective serotonin reuptake inhibitors, and antispasmodics. The Guideline Panel reviewed the evidence and used the Evidence-to-Decision Framework to develop recommendations. The panel agreed on 9 recommendations for the management of patients with IBS-C. The panel made a strong recommendation for linaclotide (high certainty) and conditional recommendations for tenapanor, plecanatide, tegaserod, and lubiprostone (moderate certainty), polyethylene glycol laxatives, tricyclic antidepressants, and antispasmodics (low certainty). The panel made a conditional recommendation against the use of selective serotonin reuptake inhibitors (low certainty).

AGA Clinical Practice Guideline on the Pharmacological Management of Irritable Bowel Syndrome With Constipation.

BACKGROUND & AIMS: Irritable bowel syndrome (IBS) is a common disorder of gut-brain interaction associated with significant disease burden. This American Gastroenterological Association guideline is intended to support practitioners in decisions about the use of medications for the pharmacological management of IBS-C and is an update of a prior technical review and guideline. METHODS: The Grading of Recommendations Assessment, Development and Evaluation framework was used to assess evidence and make recommendations. The technical review panel prioritized clinical questions and outcomes according to their importance for clinicians and patients and conducted an evidence review of the following agents: tenapanor, plecanatide, linaclotide, tegaserod, lubiprostone, polyethylene glycol laxatives, tricyclic antidepressants, selective serotonin reuptake inhibitors, and antispasmodics. The Guideline Panel reviewed the evidence and used the Evidence-to-Decision Framework to develop recommendations. CONCLUSIONS: The panel agreed on 9 recommendations for the management of patients with IBS-C. The panel made a strong recommendation for linaclotide (high certainty) and conditional recommendations for tenapanor, plecanatide, tegaserod, and lubiprostone (moderate certainty), polyethylene glycol laxatives, tricyclic antidepressants, and antispasmodics (low certainty). The panel made a conditional recommendation against the use of selective serotonin reuptake inhibitors (low certainty).

Real-World Treatment Strategies to Improve Outcomes in Patients With Chronic Idiopathic Constipation and Irritable Bowel Syndrome With Constipation.

Chronic idiopathic constipation and irritable bowel syndrome with constipation are complex, overlapping conditions. Although multiple guidelines have informed healthcare providers on appropriate treatment options for patients with chronic idiopathic constipation and irritable bowel syndrome with constipation, little direction is offered on treatment selection. First-line treatment options usually include fiber and over-the-counter osmotic laxatives; however, these are insufficient for many individuals. When these options fail, prescription secretagogues (plecanatide, linaclotide, lubiprostone, and tenapanor [pending commercial availability]), or serotonergic agents (prucalopride and tegaserod) are generally preferred. Individuals experiencing concurrent abdominal pain and/or bloating may experience greater overall improvements from prescription therapies because these agents have been proven to reduce concurrent abdominal and bowel symptoms. Should initial prescription treatments fail, retrying past treatment options (if not adequately trialed initially), combining agents from alternative classes, or use of adjunctive therapies may be considered. Given the broad spectrum of available agents, therapy should be tailored by mutual decision-making between the patient and practitioner. Overall, patients need to be actively monitored and managed to maximize clinical outcomes.

Receptor-mediated activation of CFTR via prostaglandin signaling pathways in the airway.

Cystic fibrosis (CF) is a genetic disease caused by mutations of the gene encoding a cAMP-activated Cl- channel, the cystic fibrosis transmembrane conductance regulator (CFTR). CFTR modulator therapies consist of small-molecule drugs that rescue mutant CFTR. Regimens of single or combinations of CFTR modulators still rely on endogenous levels of cAMP to regulate CFTR activity. We investigated CFTR activation by the natural mediator prostaglandin E2 (PGE2) and lubiprostone (a Food and Drug Administration-approved drug known to target prostaglandin receptors) and tested the hypothesis that receptor-mediated CFTR activators can be used in combination with currently available CFTR modulators to increase function of mutant CFTR. Primary-cultured airway epithelia were assayed in Ussing chambers. Experimental CFTR activators and established CFTR modulators were applied for 24 h and/or acutely and analyzed for their effect on CFTR activity as measured by changes in short-circuit current (ISC). In non-CF airway epithelia, acute application of lubiprostone and PGE2 activated CFTR to the levels comparable to forskolin (Fsk). Pretreatment (24 h) with antagonists to prostaglandin receptors EP2 and EP4 abolished the ability of lubiprostone to acutely activate CFTR. In F508del homozygous airway epithelia pretreated with the triple combination of elexacaftor, tezacaftor, and ivacaftor (ELEXA/TEZ/IVA; i.e., Trikafta), acute application of lubiprostone was able to maximally activate CFTR. Prolonged (24 h) cotreatment of F508del homozygous epithelia with ELEXA/TEZ/IVA and lubiprostone increased acute CFTR activation by ∼60% compared with the treatment with ELEXA/TEZ/IVA alone. This work establishes the feasibility of targeting prostaglandin receptors to activate CFTR on the airway epithelia and demonstrates that cotreatment with lubiprostone can further restore modulator-rescued CFTR.

Lubiprostone for Pediatric Functional Constipation: Randomized, Controlled, Double-Blind Study With Long-term Extension.

BACKGROUND & AIMS: Pediatric functional constipation (PFC) is a common problem in children that causes distress and presents treatment challenges to health care professionals. We conducted a randomized, placebo-controlled trial (study 1) in patients with PFC (6-17 years of age) to evaluate the efficacy and safety of lubiprostone, followed by an open-label extension for those who completed the placebo-controlled phase (study 2). METHODS: Study 1 (NCT02042183) was a phase 3, multicenter, randomized, double-blind, placebo-controlled, 12-week study evaluating the efficacy and safety of lubiprostone 12 µg twice daily (BID) and 24 µg BID. Study 2 (NCT02138136) was a phase 3, long-term, open-label extension of study 1. In both studies, lubiprostone doses were based on patients' weight. Efficacy was assessed solely based on study 1, with a primary endpoint of overall spontaneous bowel movement (SBM) response (increase of ≥1 SBM/wk vs baseline and ≥3 SBMs/wk for ≥9 weeks, including 3 of the final 4 weeks). RESULTS: 606 patients were randomized to treatment (placebo: n = 202; lubiprostone: n = 404) in study 1. No statistically significant difference in overall SBM response rate was observed between the lubiprostone and placebo groups (18.5% vs 14.4%; P = .2245). Both the 12-µg BID and 24-µg BID doses of lubiprostone were well tolerated in the double-blind and extension phases, with a safety profile consistent with that seen in adult studies. CONCLUSIONS: Lubiprostone did not demonstrate statistically significant effectiveness over placebo in children and adolescents with PFC but did demonstrate a safety profile similar to that in adults. (ClinicalTrials.gov: Number: NCT02042183; Number: NCT02138136).

Review article: current and future treatment approaches for IBS with constipation.

BACKGROUND: Multiple efficacious therapies are currently available for treating irritable bowel syndrome with constipation (IBS-C). IBS-C specific survey tools that assess symptom relief, treatment satisfaction, and quality of life are important for gauging real-world effectiveness. AIMS/METHODS: This article reviews clinical trial efficacy data as well as survey data on adequate relief and quality of life from pivotal trials for lubiprostone, linaclotide, plecanatide, tenapanor, and tegaserod. A brief discussion of agents in development with novel mechanisms of action is also provided. RESULTS/CONCLUSIONS: Quality of life and symptom metrics should be standardized and continue to be represented in future IBS-C trials. The choice of agent should be tailored to probability of improving symptoms, safety, tolerability, and cost.

Focus on Pharmacotherapy for Irritable Bowel Syndrome with Constipation.

Irritable bowel syndrome with constipation is a common disorder that significantly impairs quality of life. There are now multiple classes of therapeutics that have been shown via rigorous clinical testing to improve the abdominal and bowel symptoms attributed to irritable bowel syndrome with constipation. These include the secretagogues (lubiprostone, linaclotide, plecanatide, tenapenor) and the prokinetic agent tegaserod. This article highlights the pivotal evidence for these agents and most recent treatment guidance from the major North American gastroenterological societies. When pharmaceuticals are used, a patient-specific approach based on efficacy, safety, tolerability, access, and affordability is recommended.

Safety of elobixibat and lubiprostone in Japanese patients with chronic constipation: a retrospective cohort study.

BACKGROUND: We aimed to discuss and compare reported adverse reactions and drug add-ons associated with elobixibat and lubiprostone use in chronic constipation treatment, as the safety of these drugs has not been well examined in post-marketing clinical settings. RESEARCH DESIGN AND METHODS: In this retrospective cohort study, using records of community pharmacies in Japan, we identified new users of elobixibat and lubiprostone. The Japan Pharmaceutical Association sent questionnaires regarding baseline and event data to community pharmacists. The incidence of events and hazard ratio (HR) associated with the study drugs were evaluated. RESULTS: New users of elobixibat (n = 979) and lubiprostone (n = 829) were identified (mean age: 74 and 77 years; females: 59% and 53%, respectively). Although the crude risk ratio of adverse events for elobixibat was 0.79 (95% confidence interval: 0.63-0.99), there was no significant difference in the HR for any of the common events, including drug add-ons (n ≥ 5), compared with those for lubiprostone. CONCLUSION: No new safety concerns have been raised in relation to elobixibat and lubiprostone use for treating chronic constipation, although the HR of different events varied. Further larger-scale study is needed as the estimates for events of small numbers were unstable.

Open-label study to evaluate the treatment continuation rate after a dose reduction of lubiprostone due to onset of adverse events.

OBJECTIVE: To investigate the continuation rate with a reduced lubiprostone dose (12 mcg twice daily, BD) after the onset of adverse events (AEs) in patients with chronic constipation (CC). METHODS: In this exploratory, open-label, multicenter study, patients with CC received lubiprostone 24 mcg BD and the dose was reduced to 12 mcg BD in subjects experiencing AEs. The primary objective was the continuation rate after dose reduction due to nausea/vomiting. Secondary objectives included the continuation rate after dose reduction due to diarrhea/any AE and efficacy, including changes in number of weekly bowel movements and Bristol Stool Form Scale. RESULTS: Of the 146 patients included in the study, 42 (28.8%) received lubiprostone 12 mcg BD (dose-reduced group) due to any AE. Thirty-six (85.7%) subjects in the dose-reduced group continued treatment and completed the study. 22/27 (81.5%) and 17/19 (89.5%) patients in whom the dose was reduced due to nausea/vomiting or diarrhea, respectively, continued treatment. There was no clinically relevant difference in efficacy after dose reduction. CONCLUSION: These results suggest that treatment withdrawal due to AEs associated with lubiprostone 24 mcg BD could be minimized in patients with CC after dose reduction to 12 mcg BD, thus resulting in improved long-term outcomes. CLINICAL TRIAL REGISTRATION: Japan Registry of Clinical Trials (https://jrct.niph.go.jp/latest-detail/jRCTs031180069).

Risk Factors for Adverse Events in Patients with Chronic Constipation Following Lubiprostone Administration.

INTRODUCTION: Lubiprostone is an effective treatment of chronic constipation (CC). However, as with other stimulant or osmotic laxatives, adverse events (AEs) can make it difficult to continue treatment. This article investigates AE risk factors associated with lubiprostone. METHODS: We retrospectively analyzed all 1,338 Japanese patients with CC treated at our hospital from October 2013 to July 2017. All patients were diagnosed with constipation as defined by the Roma III criteria. Enrolled patients received lubiprostone orally (24 or 48 µg daily), after which we investigated the incidence of AEs. The causative factors for diarrhea and nausea, the most common AEs, were examined by the backward logistic regression model. RESULTS: Two hundred eight (15.5%) experienced at least 1 AE. No serious AEs were associated with the study drug. The AEs reported by >1% of patients overall were diarrhea (6.1%) and nausea (4.2%). We performed a multivariate logistic regression using a backward variable selection method to investigate AE risk factors. Factors associated with higher incidence of diarrhea were patient age of 65 years or more (odds ratio: [95% confidence interval]; p value) (2.09: [1.05-4.16]; 0.035). Factors associated with greater likelihood of nausea included female gender (1.99: [1.10-3.61]; 0.023), and the chief complaint was a patient complaining of abdominal pain and fullness (2.07: [1.01-4.22]; 0.046). CONCLUSIONS: Understanding AE risk factors can help avoid unnecessary AEs and promote more effective treatment.

Real-World Comparison of Elobixibat and Lubiprostone Treatment in Patients with Chronic Constipation: A Propensity Score-Matched Analysis.

INTRODUCTION: Elobixibat is a new laxative, but its efficacy and adverse events (AEs) are insufficiently examined compared with those of other laxatives. Hence, by propensity score (PS) matching, we compared the effects and AEs between elobixibat and lubiprostone. METHODS: We retrospectively analyzed 1,887 Japanese patients with chronic constipation (CC) treated at our hospital between October 2013 and April 2020. Enrolled patients were divided into three treatment groups, namely, elobixibat (10 mg daily) (E10 group, n = 293), lubiprostone (24 µg daily) (L24 group, n = 772), and lubiprostone (48 µg daily) (L48 group, n = 822), as their first treatment. We then investigated the changes on the weekly average number of spontaneous bowel movements, stool consistency scores (SCSs), and AEs starting from the baseline until the end of the 2-week treatment. To adjust for patients' background, we performed one-to-one nearest neighbor matching without replacement between elobixibat- and lubiprostone-treated patients according to the individual estimated PSs. RESULTS: After treatment, for SCSs, both the L24 and L48 groups significantly improved compared with the E10 group (p < 0.05), but their stools were soft (Bristol Stool Form Scale: 4.8). Notably, the E10 group had less frequent AEs than the L24 group (26 [9.0%] vs. 43 [14.8%], p = 0.03). Particularly, nausea was significantly less in the E10 group than that in the L48 group (2 [0.7%] vs. 7 [2.4%], p = 0.01). CONCLUSION: Elobixibat is a beneficial drug for patients with mildly symptomatic CC and is safe to use, given its few AEs.

Systematic review with meta-analysis: lubiprostone efficacy on the treatment of patients with constipation.

BACKGROUND: Lubiprostone is a type 2 chloride channel activator that has been shown to be efficacious and safe in the treatment for chronic constipation. OBJECTIVE: To systematically review randomized clinical trials (RCTs) assessing efficacy of lubiprostone for patients with chronic idiopathic constipation (CIC), irritable bowel syndrome with predominant constipation (IBS-C) and opioid-induced constipation (OIC). METHODS: Searches were conducted in PubMed, LILACS, Cochrane Collaboration Database, and Centre for Reviews and Dissemination. Lubiprostone RCTs reporting outcomes of spontaneous bowel movements (SBM) and abdominal pain or discomfort were deemed eligible. Meta-analysis was performed calculating risk ratios and 95% confidence intervals, using the Mantel-Haenszel method and random effects model. RESULTS: Searches yielded 109 records representing 93 non-duplicate publications, and 11 RCTs (978 CIC, 1,366 IBS-C, 1,300 OIC, total = 3,644) met inclusion criteria. Qualitative synthesis showed that for CIC patients, lubiprostone is superior to placebo in terms of SBM outcomes. Meta-analysis for CIC was feasible for full responder and SBM within 24h rates, indicating superiority of lubiprostone over placebo. For IBS-C, lubiprostone was significantly superior for all SBM outcomes in follow-ups ranging from 1 week-3 months. In terms of abdominal pain, lubiprostone provided significantly better symptoms relief, particularly after 1 month of treatment. For OIC, lubiprostone was more effective than placebo for both SBM and discomfort measures. CONCLUSION: Our findings demonstrated that lubiprostone is superior to placebo in terms of SBM frequency for CIC, IBS-C and OIC. In terms of abdominal symptoms, the most pronounced effect was seen for abdominal pain in IBS-C patients.

Systematic review with meta-analysis: lubiprostone efficacy on the treatment of patients with constipation / Revisão sistemática com metanálise: eficácia da lubiprostona no tratamento de pacientes com constipação

ABSTRACT BACKGROUND: Lubiprostone is a type 2 chloride channel activator that has been shown to be efficacious and safe in the treatment for chronic constipation. OBJECTIVE: To systematically review randomized clinical trials (RCTs) assessing efficacy of lubiprostone for patients with chronic idiopathic constipation (CIC), irritable bowel syndrome with predominant constipation (IBS-C) and opioid-induced constipation (OIC). METHODS: Searches were conducted in PubMed, LILACS, Cochrane Collaboration Database, and Centre for Reviews and Dissemination. Lubiprostone RCTs reporting outcomes of spontaneous bowel movements (SBM) and abdominal pain or discomfort were deemed eligible. Meta-analysis was performed calculating risk ratios and 95% confidence intervals, using the Mantel-Haenszel method and random effects model. RESULTS: Searches yielded 109 records representing 93 non-duplicate publications, and 11 RCTs (978 CIC, 1,366 IBS-C, 1,300 OIC, total = 3,644) met inclusion criteria. Qualitative synthesis showed that for CIC patients, lubiprostone is superior to placebo in terms of SBM outcomes. Meta-analysis for CIC was feasible for full responder and SBM within 24h rates, indicating superiority of lubiprostone over placebo. For IBS-C, lubiprostone was significantly superior for all SBM outcomes in follow-ups ranging from 1 week-3 months. In terms of abdominal pain, lubiprostone provided significantly better symptoms relief, particularly after 1 month of treatment. For OIC, lubiprostone was more effective than placebo for both SBM and discomfort measures. CONCLUSION: Our findings demonstrated that lubiprostone is superior to placebo in terms of SBM frequency for CIC, IBS-C and OIC. In terms of abdominal symptoms, the most pronounced effect was seen for abdominal pain in IBS-C patients.

RESUMO CONTEXTO: Lubiprostona é um ativador de canal de cloreto tipo 2 que tem se demonstrado eficaz e seguro no tratamento da constipação crônica. OBJETIVO: Revisar sistematicamente ensaios clínicos randomizados (ECRs) avaliando a eficácia da lubiprostona para pacientes com constipação idiopática crônica (CIC), síndrome do intestino irritável com constipação predominante (IBS-C) e constipação induzida por opioide (OIC). MÉTODOS: Buscas foram conduzidas no PubMed, LILACS, Cochrane Collaboration Database e Centre for Reviews and Dissemination. ECRs de lubiprostona relatando desfechos de movimentos intestinais espontâneos (SBM) e dor ou desconforto abdominal foram considerados elegíveis. Metanálise foi realizada calculando razão de riscos e intervalos de confiança de 95%, utilizando o método de Mantel-Haenszel e modelo de efeitos aleatórios. RESULTADOS: As buscas identificaram 109 registros representando 93 publicações não-duplicadas e 11 ECRs (978 pacientes de CIC, 1366 de IBS-C e 1300 OIC, total = 3644) preencheram os critérios de inclusão. Síntese qualitativa mostrou que, para pacientes com CIC, a lubiprostona foi superior ao placebo em termos de desfechos SBM. Metanálise para CIC foi possível para os desfechos de responder completo e taxa de SBM em 24 horas, indicando superioridade da lubiprostona sobre o placebo. Para IBS-C, lubiprostona foi significativamente superior para todos os desfechos de SBM em tempos de seguimento variando de 1 semana a 3 meses. Em termos de dor abdominal, lubiprostona proporciono alívio dos sintomas significativamente melhor, particularmente após 1 mês de tratamento. Para OIC, lubiprostona foi mais efetiva do que placebo tanto para medidas de SBM quando de desconforto abdominal. CONCLUSÃO: Nossos achados demonstraram que lubiprostona é superior ao placebo em termos de frequência de SBM para CIC, IBS-C e OIC. Em termos de sintomas abdominais, o efeito mais pronunciado foi visto para dor abdominal em pacientes com IBS-C.

Medications for constipation in 2020.

PURPOSE OF REVIEW: Chronic constipation is a common problem that substantially impacts the quality of life of patients and families, healthcare professionals, and resources. The purpose of this review is to discuss the medications that are available for management of chronic constipation, including medications that have been approved by the FDA for adults, other been studied in pediatrics now, and might become available within the upcoming years. RECENT FINDINGS: Recent developments in the evaluation of childhood constipation are providing a better understanding into defecation disorders in children and not only new therapies are becoming available, including medications, but also other therapies, such as biofeedback for treatment of functional defecation disorders, electrical stimulation, and surgeries. The aim of this article is to provide an update on the medications that are available for management of chronic constipation, especially with the development and study of newer medications, such as Linaclotide and Lubiprostone with promising results in both adult and pediatric patients. SUMMARY: This review will help us identify and have a better understanding regarding what medications are available for use and the indications, so that we can better manage patients with chronic constipation. VIDEO ABSTRACT.

Effect of lubiprostone on vinca alkaloid-induced constipation in patients with hematological malignancies: a propensity score-matched analysis.

Patients receiving vinca alkaloids for hematological malignancies frequently experience constipation that is unresponsive to laxatives. Research on treatment of vinca alkaloid-induced constipation is limited. This study aimed to determine whether the chloride channel activator lubiprostone ameliorates vinca alkaloid-induced constipation in patients with hematological malignancies. In this retrospective cohort study, vinca alkaloid-induced constipation (grade ≥ 3 using the Common Terminology Criteria for Adverse Events) was investigated in patients treated for hematological malignancies between July 2014 and June 2019 who had already been prescribed osmotic laxatives and additionally received either a stimulant laxative or lubiprostone. Univariate and multivariate analyses were performed to identify the risk factors for persistent constipation after introduction of the second laxative. A propensity score model was used to match 67 patients taking a stimulant laxative and 67 treated with lubiprostone, and the occurrence of intractable constipation was compared between groups. Overall, 203 patients were included, among whom 50 (25%) had constipation. On multivariate analysis, body mass index, opioid use, and addition of lubiprostone were independently associated with constipation. Patients treated with lubiprostone were significantly less likely to experience intractable constipation than did those treated with stimulant laxatives (10% vs. 34%, P = 0.002). Moreover, post-constipation diarrhea was significantly less frequent among patients treated with lubiprostone (42% vs. 63%, P = 0.024). Lubiprostone was more effective than stimulant laxatives at treating vinca alkaloid-induced intractable constipation in patients with hematological malignancies, and its use could enable safe vinca alkaloid chemotherapy.