Treating Opioid Dependence With Injectable Extended-Release Naltrexone (XR-NTX): Who Will Respond?

Edward V Nunes, Evgeny Krupitsky, Walter Ling, Jacqueline Zummo, Asli Memisoglu, Bernard L Silverman, David R Gastfriend, Edward V Nunes, Evgeny Krupitsky, Walter Ling, Jacqueline Zummo, Asli Memisoglu, Bernard L Silverman, David R Gastfriend

Abstract

Objectives: Once-monthly intramuscular extended-release naltrexone (XR-NTX) has demonstrated efficacy for the prevention of relapse in opioid dependence, providing an alternative to agonist or partial agonist maintenance (ie, methadone and buprenorphine). The question remains, for whom is this unique treatment most efficacious and can patient-treatment matching factors be identified?

Methods: A moderator analysis was conducted on a previously reported 24-week, placebo-controlled, multisite, randomized controlled trial of XR-NTX (n = 126) versus placebo (n = 124) among recently detoxified opioid-dependent adults in Russia, which showed XR-NTX superior to placebo in proportion of opioid abstinent weeks. The moderator analysis examined a dichotomous indicator of good clinical response-achieving at least 90% of weeks abstinent over the 24-week trial. A series of logistic regression models were fit for this outcome as functions of treatment (XR-NTX vs placebo), each baseline moderator variable, and their interactions. The 25 baseline variables included demographics, clinical severity (Addiction Severity Index, SF-36, and Clinical Global Impression-Severity), functioning (EQ-5D), craving, and HIV serostatus (HIV+).

Results: More XR-NTX patients achieved 90% abstinence (64/126, 51%) versus placebo (39/124, 31%; P = 0.002). There were no significant interactions between baseline variables and treatment. There was a significant main effect of Clinical Global Impression-Severity score (P = 0.02), such that higher severity score was associated with a lower rate of Good Clinical Response.

Conclusions: The absence of significant baseline by treatment interactions indicates that no patient-treatment matching variables could be identified. This suggests that XR-NTX was effective in promoting abstinence from opioids across a range of demographic and severity characteristics.

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

FIGURE 1.
FIGURE 1.
Good clinical response (1) stratified by baseline Clinical Global Impression-Severity of illness and HIV serostatus. Top panel: Clinical Global Impression-Severity (CGI-S) (2) is dichotomized into lower severity (scores 1-4: normal, borderline, mildly, and moderately ill) and higher severity (scores: 5 through 7: markedly, severely, and among the most ill). Bottom panel: HIV serostatus (positive vs negative). (1) Good Clinical Response is defined as 90% or more urine-confirmed abstinent weeks over the 24 weeks of the trial. (2) The main effect of baseline CGI-S is significant (P = 0.02); the baseline CGI-S by treatment interaction is not significant (P = 0.09). (3) Neither the main effect of baseline HIV serostatus (P = 0.06) nor the HIV serostatus by treatment interaction (P = 0.07) is significant. Values from 250 opioid-dependent patients who entered a 24-week randomized, placebo-controlled trial of extended-release naltrexone (XR-NTX) versus placebo.

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