Efficacy of Subcutaneous Methylnaltrexone in the Treatment of Opioid-Induced Constipation: A Responder Post Hoc Analysis

Abstract

Early response to ≥2 of first four doses of methylnaltrexone identified patients who demonstrated a particularly robust effect of treatment over the duration of use.

Opioid-induced constipation: advances and clinical guidance

“…PAC-SYM scores, specifically the stool and rectal symptoms, were improved with methylnaltrexone once daily or every other day compared with placebo, with no effect on pain scores [Iyer et al 2011]. An early response suggested excellent outcome; thus 81% had at least three RFBMs/week if there was an early response to methylnaltrexone [Michna et al 2011b]. Abdominal pain and nausea were the most common adverse events reported [Iyer et al 2011;Michna et al 2011].…”

Opioid-induced constipation in chronic noncancer pain

“…Currently available, FDA-approved treatment options include the peripheral m-opioid receptor antagonists MNTX [36][37][38]45] as a subcutaneous injectable and the orally available naloxegol [35 && ,47-49] to provide symptom relief. Furthermore, lubiprostone, a bicyclical fatty acid and activator of intestinal CIC-2 was approved for the treatment of patients with noncancer pain and nonmethadone based OIC [39,40 & ,41 && ] (https://www.amitizahcp.com/ efficacy-indication-3/#isi).…”

“…Those with RFBMs after at least two of first four doses averaged 4.8 RFBMs/week versus 2.0 RFBMs/week for those with less than two of four (P < 0.0001). Early response to at least two of first four doses of MNTX identified patients who demonstrated a particularly robust effect of treatment over the duration of use [38].…”

“…A post-hoc analysis of this RCT study [37] was conducted to identify patients who achieved maximal treatment effect based on response to initial four MNTX doses [38]. Patients with OIC and chronic noncancer pain who received 12 mg subcutaneous MNTX daily for 4 weeks were assessed if response to the first four MNTX doses predicted overall response during the study.…”

“…Methylnaltrexone (MNTX) became the first FDAapproved peripheral m-opioid receptor antagonist (PAMORA) for OIC in patients with advanced illness in 2008 [32,36] (www.accessdata.fda.gov/ drugsatfda_docs/nda/2008/021964s000TOC.cfm). More recently, in 2014 MNTX as subcutaneous injection was also FDA approved for OIC in patients with chronic, nonmalignant pain [37,38] (http://www.salix.com/products/relistor/; https:// shared.salix.com/shared/pi/relistor-pi.pdf?id=825 1081). Similarly, Naloxegol, the first orally available pegylated derivative of the m-opioid receptor antagonist naloxone, was also FDA approved for OIC in patients with noncancer pain in 2014 (http://www.fda.gov/newsevents/newsroom/press announcements/ucm414620.htm; http://www.azpi central.com/movantik/movantik.pdf) [35 && ].…”