Buprenorphine-Naloxone Advised Over Extended-Release Naltrexone for Opioid Use Disorder

December 18, 2018

By Will Boggs MD 

NEW YORK—Buprenorphine-naloxone should be favored over extended-release naltrexone as first-line treatment for opioid use disorder (OUD) in adults, according to a cost-effectiveness analysis.

"Both medications were effective at treating opioid use disorder with regard to time abstinent from opioid use and health-related quality-of-life," Dr. Sean M. Murphy from Weill Cornell Medical College, New York City, told Reuters Health by email. "However, the higher cost of extended-release naltrexone and additional costs associated with detoxification prior to administering this medication, resulted in buprenorphine-naloxone being the better value to the healthcare sector, among patients who require detoxification before initiating extended-release naltrexone."

Buprenorphine-naloxone is an oral combination, whereas naltrexone is commonly administered as a monthly extended-release injection. There is limited evidence regarding the relative economic value of these treatments.

Dr. Murphy's team evaluated the cost-effectiveness of these two pharmacotherapies as 24-week interventions with 12 additional weeks of observation, using cost per quality-adjusted life-year (QALY) from the healthcare sector and societal perspectives as primary outcomes.

The estimated cost of extended-release naltrexone was $704, and the average costs of generic buprenorphine-naloxone were $1.20 per 4 mg and $2.17 per 8 mg.

From the healthcare sector perspective, the average total costs for 24 weeks of treatment were significantly higher for extended-release naltrexone ($18,923) than for buprenorphine-naloxone ($13,606), and both outcomes were slightly better for buprenorphine-naloxone (0.797 annualized QALYs and 0.533 annualized abstinent years) than for extended-release naltrexone (0.790 and 0.476, respectively).

The cost differences between the treatments decreased by 36 weeks and became statistically nonsignificant, according to the December 17th Annals of Internal Medicine online report.

Results were similar from the societal perspective, although the total costs and outcomes did not differ significantly between the groups at 24 or 36 weeks.

The incremental cost-effectiveness ratio point estimates indicated that buprenorphine-naloxone dominated extended-release naltrexone, and acceptability curves indicated low likelihoods that extended-release naltrexone would be considered cost-effective relative to buprenorphine-naloxone from either the healthcare sector or societal perspectives if the recommended range of $100,000-$200,000 per QALY were used.

"These are both very effective medications for the treatment of opioid use disorder," Dr. Murphy said. "Narrowing the cost gap by identifying the best possible patients for each medication, lowering the cost of extended-release naltrexone, and shortening or eliminating the induction period could improve its relative economic value, thereby increasing its attractiveness to payers and allowing more people to access either alternative according to their clinical needs and preferences."

"In addition to the clinical trial on which Murphy and colleagues based their study, other evidence is mounting that buprenorphine-naloxone is more efficacious and safer than extended-release naltrexone in the real world," write Dr. Joshua A. Barocas and Dr. Richard Saitz from Boston University School of Medicine, in an editorial.

"We should evaluate treatment for opioid addiction as we do for other chronic medical diseases, by assessing efficacy, costs, risks, and the likelihood of success, and not on the basis of beliefs, which partly underlie regulations that restrict access," they conclude. "Like treatment for many other chronic disorders, OUD treatment comes in many forms and is often lifelong. Basing medical decisions on beliefs about medications does nothing to help the growing pool of those with OUD, who if untreated are likely to fall victim to an overdose."

Dr. Andrew J. Saxon, director of University of Washington School of Medicine's Center of Excellence in Substance Abuse Treatment and Education, in Seattle, told Reuters Health by email, "The main factor in the choice remains the patient's willingness to undergo complete withdrawal from opioids and remain abstinent for up to 7-10 days (although as noted in the paper oftentimes this interval can be shortened)."

"If the patient is interested in undertaking this withdrawal, the patient is a candidate for extended-release naltrexone," he said. "If the patient does not have interest in pursuing withdrawal, then, per force, the initial choice should be buprenorphine/naloxone, and this choice will be the one appropriate for the majority of patients. If we have a patient who has had prior experience with one or both of these medications, prior history of response can be taken into account."

"I am not so impressed by the cost differences that I would use that as a large factor in my clinical decision making," Dr. Saxon said.

"New products that are 30-day extended-release formulations of buprenorphine are being introduced," he added. "The recent and upcoming availability of these formulations may change the decision-making process about which formulations and which medications to use for which patients as we learn more about these new formulations."

Dr. Walter Ling from University of California, Los Angeles, who has extensively researched treatments for cocaine dependence, told Reuters Health, "This is not surprising. It corresponds with the just released findings of the Institute for Clinical and Economic Review (the other ICER), which, incidentally, puts the annual cost per QALY gained for extended-release naltrexone at approximately one million dollars."

"Still, there continues to be efforts . . . to promote extended-release naltrexone by minimizing the upfront difficulties of successful extended-release naltrexone induction," he said. "This serious upfront cost is borne not by the health care system or by society, but by the patients themselves in the form of risk for relapse, incarceration, overdose death, etc., etc."

"Some select patients do benefit from extended-release naltrexone; most don't," Dr. Ling said. "And most patients, given all the facts and the choices, would rather not take naltrexone in all forms. Perhaps intuitively they know something. Unlike the agonists and partial agonists, we have no data on the long-term treatment of naltrexone. We don't know that it is a good idea to have our endorphin system chronically blocked by an antagonist."

Dr. Saxon noted that he recently served on an advisory board for Alkermes, the company that makes extended-release naltrexone.

SOURCE: http://bit.ly/2A3M4xH

Ann Intern Med 2018.

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I have successfully treated hundreds of addicts with Vivitrol over a 1-2 year treatment period with no ill effects.  Authors statement regarding prolonged opioid anatagonist exposure is unfounded and says nothing of well documented effects of prolonged opioid usage.  These studies comment nothing on compliance, which is a significant issue in oral buprenorphine, as well as risk with benzodiazepenes.  Nor does it comment on costs related to residential treatment modalities in buprenorphine vs vivitrol treatment.  Other studies have shown equivalence in treatment.