{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T22:33:11Z","timestamp":1790289191607,"version":"4.1.0"},"reference-count":53,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2019,1,16]],"date-time":"2019-01-16T00:00:00Z","timestamp":1547596800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Gastro and Hepatol"],"published-print":{"date-parts":[[2019,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Aim<\/jats:title><jats:p>Opioid\u2010induced constipation (OIC) is a frequent adverse event (AE) that impairs patients' quality of life (QOL). Peripherally acting \u03bc\u2010opioid receptor antagonists (PAMORAs) have been recognized as a treatment option for OIC, but the effect consistent across the studies has not been evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We conducted a quantitative meta\u2010analysis to explore the efficacy of PAMORA for OIC (registered with PROSPERO: CRD42018085298). We systematically searched randomized controlled trials (RCTs) in Medline, Embase, and Central databases. Change from baseline in spontaneous bowel movements, pooled proportion of responders, QOL, and AEs were calculated and compared with results in placebo cases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We included 31 RCTs with 7849 patients. A meta\u2010analysis revealed that patients under PAMORA therapy had considerably improved spontaneous bowel movement from baseline compared with those given placebo (20 RCTs; mean difference, 1.43; 95% confidence interval [CI], 1.18\u20131.68; <jats:italic>n<\/jats:italic>\u00a0=\u00a05622) and more responded (21 RCTs; risk ratio [RR], 1.81; 95% CI, 1.55\u20132.12; <jats:italic>n<\/jats:italic>\u00a0=\u00a04821). Moreover, QOL of patients receiving PAMORA was significantly better (8 RCTs; mean difference, \u22120.22; 95% CI, \u22120.28 to \u22120.17; <jats:italic>n<\/jats:italic>\u00a0=\u00a02884). AEs were increased significantly in the PAMORA group (26 RCTs; RR, 1.10; 95% CI, 1.06\u20131.15; <jats:italic>n<\/jats:italic>\u00a0=\u00a07715), especially in gastrointestinal disorders, whereas serious AEs were not significant (17 RCTs; RR, 1.04; 95% CI, 0.85\u20131.28; <jats:italic>n<\/jats:italic>\u00a0=\u00a05890).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Peripherally acting \u03bc\u2010opioid receptor antagonist has been shown to be effective and durable for patients with OIC and is the only drug with confirmed evidence in meta\u2010analysis. The possibility of publication bias was the limitation of this study.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jgh.14586","type":"journal-article","created":{"date-parts":[[2018,12,31]],"date-time":"2018-12-31T22:18:38Z","timestamp":1546294718000},"page":"818-829","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Peripherally acting \u03bc\u2010opioid antagonist for the treatment of opioid\u2010induced constipation: Systematic review and meta\u2010analysis"],"prefix":"10.1111","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0171-0218","authenticated-orcid":false,"given":"Kenichi","family":"Nishie","sequence":"first","affiliation":[{"name":"Department of Respiratory Medicine Iida Municipal Hospital  Iida Nagano Japan"},{"name":"The First Department of Internal Medicine Shinshu University School of Medicine  Matsumoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhei","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Shinshu University Hospital  Matsumoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayoshi","family":"Yamaga","sequence":"additional","affiliation":[{"name":"Department of Occupational Therapy Health Science University  Fujikawaguchikomachi Yamanashi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoto","family":"Horigome","sequence":"additional","affiliation":[{"name":"Department of Digestive Surgery Iida Municipal Hospital  Iida Nagano Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayuki","family":"Hanaoka","sequence":"additional","affiliation":[{"name":"The First Department of Internal Medicine Shinshu University School of Medicine  Matsumoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,1,16]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.14694\/EdBook_AM.2015.35.e593"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajgsup.2014.7"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.3111\/13696998.2013.851082"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11894-013-0344-2"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.2165\/11634970-000000000-00000"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/15360280903098440"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.5055\/jom.2009.0014"},{"key":"e_1_2_5_9_1","first-page":"613","article-title":"Management of opioid\u2010induced bowel dysfunction in cancer patients","volume":"12","author":"Tamayo AC","year":"2004","journal-title":"Support Care Cancer"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/ijcp.12718"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9610(01)00782-6"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.12417"},{"key":"e_1_2_5_13_1","first-page":"1837","article-title":"Opioid\u2010induced constipation and bowel dysfunction: a clinical guideline","volume":"18","author":"Muller\u2010Lissner S","year":"2017","journal-title":"Pain Med."},{"key":"e_1_2_5_14_1","first-page":"e123","article-title":"Preferred reporting items for systematic reviews and meta\u2010analyses: the PRISMA statement","volume":"3","author":"Moher D","year":"2009","journal-title":"Open Med."},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2017.73.0853"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.70.8453"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-1253(17)30105-X"},{"key":"e_1_2_5_18_1","unstructured":"HigginsJPT GreenS.Cochrane handbook for systematic reviews of interventions version 5.1.0: the Cochrane collaboration 2011."},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.283.3.367"},{"key":"e_1_2_5_20_1","doi-asserted-by":"crossref","first-page":"S94","DOI":"10.1016\/j.jpain.2016.01.456","article-title":"(479) A phase 2a, randomized, double\u2010blind, placebo\u2010controlled, single ascending\u2010dose study to evaluate the safety and efficacy of naldemedine in patients with chronic non\u2010cancer pain and opioid\u2010induced bowel dysfunction","volume":"17","author":"Webster L","journal-title":"J. Pain"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/pm\/pnw325"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2007.11.008"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2013.04.024"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0707377"},{"key":"e_1_2_5_25_1","first-page":"39","article-title":"Methylnaltrexone for treatment of opioid\u2010induced constipation in advanced illness patients","volume":"7","author":"Slatkin N","year":"2009","journal-title":"J. Support Oncol."},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2012.07.085"},{"key":"e_1_2_5_27_1","unstructured":"RossV Yu\u2010PingL UllrichS NeilS LynnW DanielC.Phase 2b evaluation of TD\u20101211 in opioid\u2010induced constipation. American Academy of Pain Management 2012 Annual Clinical Meeting. Phoenix AZ American Academy of Pain Management 2012."},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/papr.12535"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpain.2004.12.001"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpain.2010.11.008"},{"key":"e_1_2_5_31_1","article-title":"Long\u2010term safety and efficacy of naldemedine for the treatment of opioid\u2010induced constipation in subjects with chronic non\u2010cancer pain receiving opioid therapy: results from a 52\u2010week phase 3 clinical trial in PAINWeek Abstract Book 2016","volume":"128","author":"Lynn WS","year":"2016","journal-title":"Postgrad. Med."},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpain.2010.06.012"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpain.2010.06.013"},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1310246"},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.1089\/jpm.2014.0362"},{"key":"e_1_2_5_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/jhm.943"},{"key":"e_1_2_5_37_1","unstructured":"Efficacy and Safety Study of CB\u20105945 for the Treatment of Opioid\u2010Induced Constipation.https:\/\/ClinicalTrials.gov\/show\/NCT01901302."},{"key":"e_1_2_5_38_1","unstructured":"The Efficacy and Safety Study of CB\u20105945 for the Treatment of Opioid\u2010Induced Constipation.https:\/\/ClinicalTrials.gov\/show\/NCT01901341."},{"key":"e_1_2_5_39_1","unstructured":"Safety Study of CB\u20105945 for the Treatment of Opioid\u2010Induced Constipation.https:\/\/ClinicalTrials.gov\/show\/NCT01696643."},{"key":"e_1_2_5_40_1","doi-asserted-by":"crossref","first-page":"S513","DOI":"10.14309\/00000434-201110002-01341","article-title":"TD\u20101211 demonstrates constipation\u2010relieving effects, including decrease in rescue laxative use, in patients with opioid\u2010induced constipation 2011 ACG presidential poster","volume":"106","author":"Vickery R","year":"2011","journal-title":"Am. J. Gastroenterol."},{"key":"e_1_2_5_41_1","unstructured":"RoennJ. TackJ. BarkerP. LoweE. FleischmannCMS.Challenges in patient recruitment during KODIAC\u201006 a randomized placebo\u2010controlled multicentre phase III trial of naloxegol in patients with neoplasia and opioid\u2010induced constipation (OIC).MASCC\/ISOO International Symposium on Supportive Care in Cancer. Berlin Germany: Support Care Cancer2013."},{"key":"e_1_2_5_42_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1526-4637.2002.02045.x"},{"key":"e_1_2_5_43_1","doi-asserted-by":"publisher","DOI":"10.1213\/ANE.0b013e31820568af"},{"key":"e_1_2_5_44_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdw317"},{"key":"e_1_2_5_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2018.01.021"},{"key":"e_1_2_5_46_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1526-4637.2008.00495.x"},{"key":"e_1_2_5_47_1","doi-asserted-by":"publisher","DOI":"10.2147\/CEOR.S61602"},{"key":"e_1_2_5_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpainsymman.2010.02.019"},{"key":"e_1_2_5_49_1","doi-asserted-by":"publisher","DOI":"10.1080\/00325481.2016.1149017"},{"key":"e_1_2_5_50_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40273-016-0454-4"},{"key":"e_1_2_5_51_1","unstructured":"Food and Drug Administration Center for Drug Evaluation and Research (2008)"},{"key":"e_1_2_5_52_1","doi-asserted-by":"publisher","DOI":"10.1097\/SLA.0b013e31824a36cc"},{"key":"e_1_2_5_53_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.sla.0000232538.72458.93"},{"key":"e_1_2_5_54_1","doi-asserted-by":"publisher","DOI":"10.1177\/1074248418760239"}],"container-title":["Journal of Gastroenterology and Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjgh.14586","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jgh.14586","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jgh.14586","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jgh.14586","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,10]],"date-time":"2023-09-10T20:11:35Z","timestamp":1694376695000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jgh.14586"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,1,16]]},"references-count":53,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2019,5]]}},"alternative-id":["10.1111\/jgh.14586"],"URL":"https:\/\/doi.org\/10.1111\/jgh.14586","archive":["Portico"],"relation":{},"ISSN":["0815-9319","1440-1746"],"issn-type":[{"value":"0815-9319","type":"print"},{"value":"1440-1746","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,1,16]]},"assertion":[{"value":"2018-05-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-12-22","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-01-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}