Case Study: Therapeutic Interchange in Patients Being Treated for Opioid Dependence - Rationale and Real-World Experience

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BACKGROUND

Opioid Abuse: A Growing Problem

Among all countries, the United States uses a disproportionate supply of the world’s opioid pain relievers. It has been estimated that 81% of oxycodone-based products and almost all hydrocodone-based products consumed globally are used in the United States. Opioid use has increased over time: the number of prescriptions for opioids grew from about 76 million in 1991 to nearly 207 million in 2013.1

Opioid dependence accounts for the largest proportion of addiction to prescription substances. In 2013, results of the National Survey on Drug Use and Health indicated that 1.9 million individuals in the United States have an addiction to prescription opioids and an additional 517,000 individuals were addicted to heroin.2 Moreover, an even larger segment of the population—the estimated 6 to 8 million Americans using prescription opioids for long-term management of pain—are at risk for developing opioid dependence.3 Among patients using chronic opioid analgesic therapy, the overall risk of developing opioid dependence is low; however, the risk is higher in those with a history of abuse or previous addiction.4,5

Medical Consequences of Opioid Abuse

The rising rate of opioid abuse has led to an increase in emergency department (ED) visits for nonmedical opioid use, from 144,600 visits in 2004 to 305,900 visits in 2008, and a further increase to 420,000 ED visits in 2011.1,6 Opioid use is also associated with increased overall mortality: drug overdoses are one of the most common causes of death among individuals using opioids for nonmedical purposes.7 Since 1999, the number of unintentional deaths occurring annually as a result of prescription opioid overdoses has more than quadrupled.8 In 2013, opioid pain reliever use was a factor in more than 16,000 deaths (Figure).9 In addition, nonmedical use of prescription opioids is often a gateway to use of heroin, an illicit opioid. The results of one study showed that approximately 4 out of 5 (79.5%) new heroin users reported previous nonmedical use of prescription opioids.10 More than 8000 deaths occurred in relation to heroin use in 2013.9 In 2014, more deaths occurred due to drug overdoses in the United States than during any previous year on record. Nearly 500,000 deaths due to drug overdoses were recorded from 2000 to 2014. The main drugs associated with death due to drug overdose are opioids, primarily heroin and prescription pain relievers. In 2014, the number of deaths due to drug overdose in the United States was approximately one-and-a-half times more than the number of deaths due to motor vehicle crashes. Opioids were a factor in 28,647 deaths in 2014 (61% of all deaths due to overdose). Since 2000, the rate of opioid overdoses has increased 3-fold.11 In addition, opioid use is associated with an increased risk of developing HIV and viral hepatitis due to contact with infected blood or body fluids during unprotected sex or through sharing syringes or injection paraphernalia.7 Together, these and other factors contribute to the societal burden of opioid abuse in the United States.

Economic Impact of Opioid Dependence

According to one estimate, annual opioid dependence—related costs exceed $55 billion (in 2007 dollars), including $25.0 billion in direct healthcare costs and $25.6 billion in lost productivity. Excess medical and prescription costs constituted the bulk of the healthcare costs.12 In another estimate, the Coalition Against Insurance Fraud tallied $72.5 billion in costs related to opioid dependence, including $24.9 billion each year paid by private insurers.6,13 Individuals with opioid dependence incur an average of $10,627 in excess costs per patient per year versus comparable patients without opioid dependence.14

Management of Opioid Dependence

To help address the problem of opioid abuse, the American Society of Addiction Medicine developed a national practice guideline for the treatment of opioid dependence using a combination of scientific evidence and clinical knowledge from a group of 10 multidisciplinary, multispecialty experts and researchers. This guideline is the first to include all FDA-approved medications in a single guideline document and to address the needs of special populations with opioid dependence, such as pregnant women and adolescents.15 The guidelines recommend use of a treatment regimen that takes into account many patient-specific factors, and may include pharmacologic and psychosocial interventions.15,16

The likelihood of treatment success depends on several factors. Factors associated with a greater risk of relapse include a longer duration of opioid dependence prior to detoxification and use of opioids as a young adult.17 Conversely, factors associated with success include use of medication, including buprenorphine, in combination with intensive psychosocial therapy, rather than intensive psychosocial therapy alone.18 In many cases, maintenance treatment must continue over an extended period of time.19

Available Treatments for Opioid Dependence

Currently available active ingredients in FDA-approved medications for the treatment of opioid dependence include the opioid agonists methadone and buprenorphine and the opioid antagonists naltrexone and naloxone. Methadone is a full mu opioid agonist; the administration of methadone should be monitored due to the potential for misuse and diversion until the patient’s clinical response and behavior demonstrate that the prescribing of nonmonitored doses is appropriate. The partial mu agonist buprenorphine may be preferable to methadone as it may be prescribed in the office setting. As a partial agonist, buprenorphine prevents withdrawal symptoms but limits the experience of euphoria. Both methadone and buprenorphine are associated with respiratory depression when used in association with CNS depressants including alcohol, other opioids, and illicit drugs. Finally, the fast-acting opioid antagonist naloxone and the long-acting opioid antagonist naltrexone block the effects of opioids. Naloxone is used to reverse opioid overdose and is available in injectable (for life-threatening situations) and sublingual formulations. Naltrexone is used to prevent relapse to opioid use and is available in oral and extendedrelease injection formulations.15,20 Several formulations that contain the medications buprenorphine and naloxone are available, including tablets and sublingual film. Because naloxone is not bioavailable to a clinically significant degree when administered orally, sublingually, or buccally, patients using medication-assisted treatment through the appropriate route of administration will experience the appropriate pharmacologic effect of the partial opioid agonist buprenorphine, which is bioavailable through these routes of administration. However, in patients who attempt to abuse the medication by adulterating the product and injecting it, the euphoric effect of parenterally administered buprenorphine is blocked by naloxone, which is fully bioavailable and active when administered parenterally. These patients may experience symptoms of withdrawal.20

Buprenorphine/Naloxone Combination Therapy

According to data collected by IMS Health, use of opioid dependence treatments in the buprenorphine/naloxone category has been growing at a rate of 8% to 12% over the past 5 years.21 One of these products, Suboxone® (buprenorphine/naloxone) CIII sublingual film, was the 21st most prescribed drug in the United States between July 2013 and June 2014.22 As noted in police case reports, in 2013, buprenorphine was the fourth most diverted medication in the United States for illicit use. Individuals may use diverted buprenorphine/naloxone medications to prevent withdrawal symptoms outside of a treatment program. In addition, a minority abuse these products to experience the euphoria they induce.23

ZUBSOLV® (buprenorphine and naloxone) sublingual tablet CIII formulation contains 30% less of the active buprenorphine than the Suboxone film formulation of buprenorphine/naloxone while delivering a comparable therapeutic effect.24 In this category, where substantial diversion potential exists, a formulation that contains less buprenorphine may help reduce the overall amount of buprenorphine diverted for use in a nonmedical setting. In addition to supplying less buprenorphine for potential illicit use, in a study of healthy volunteers, select attributes such as taste and mouth-feel of ZUBSOLV are preferred by more than 80% of those who tried both medications.25

CASE STUDY: THERAPEUTIC INTERCHANGE FROM SUBOXONE FILM TO ZUBSOLV TABLET—ONE PLAN’S EXPERIENCE

Editors from The American Journal of Managed Care (AJMC) sat down with Sheila Arquette, RPh, director of pharmacy at Independent Health, to learn about the experience of Independent Health with therapeutic interchange from Suboxone Film to ZUBSOLV Tablet, including the rationale for the formulary change, the impact on providers and patients, and outcomes.a

Headquartered in Buffalo, New York, Independent Health is a not-for-profit health plan serving nearly 400,000 members in the 8 counties of western New York, including 130,000 commercial members and 75,000 Medicaid members.

a Sheila Arquette is not a paid consultant of Orexo US, Inc and her comments and the data presented represent her views or interpretation and are not necessarily endorsed by Orexo US, Inc.

AJMC: Were there specific circumstances or concerns that prompted Independent Health to consider therapeutic interchange from Suboxone Film to ZUBSOLV Tablet? What was the rationale for the interchange?

Everyone has seen the information in the press about overdoses and substance abuse. As an organization, we have always been very committed and focused on appropriate opioid prescribing. Over the past 10 years or so, hydrocodone-containing products have become our numberone prescribed medication. We’re definitely focused on being good community stewards, trying to ensure that patients who are in pain are effectively treated for pain while being cognizant of the widespread societal issue of opioid abuse and diversion.

For the last probably 5 to 7 years, we’ve sponsored an annual pain medication continuing education program for primary care physicians. We bring in local thought leaders, pain management

experts, and people from the DEA and law enforcement in an effort to raise awareness regarding the huge issue that we’re having with these medications, especially with our younger folks.

We knew that a good treatment option was also something that was becoming very popular on the street. We thought, “What else could be done?” We also heard about other health plans that had made the change and the results of the switch in terms of utilization, plan savings, and appropriate prescribing.

The rationale for the change was to provide a clinically comparable, cost-effective alternative to Suboxone. As both products contain the same active ingredients, we felt the disruption to patients would be minimal. We are always looking for ways to better manage costs while continuing to provide a clinically strong and sound, value-based formulary. At the same time, we are also

looking for opportunities to reduce abuse and diversion.

ARQUETTE:

AJMC: With regard to outcomes, what were your expectations in terms of benefits of the interchange?

ARQUETTE:

We anticipated that the interchange would result in decreased pharmacy plan spend for this therapeutic category with no impact on clinical effect or patient response. As an ancillary effect, we felt that the interchange could potentially help curb abuse and diversion.

AJMC: How did the process of implementing the therapeutic interchange from Suboxone Film to ZUBSOLV Tablet get started?

ARQUETTE:

My job was to put together a comprehensive clinical overview and management plan and then present it to plan leadership, to evaluate whether there was a desire to move in this direction. We would take it further if there was interest. I must admit, initially, the interchange didn’t seem to be a big issue. I was pretty comfortable thinking, “I’m asking patients and prescribers to switch to a different product that has the same active ingredients and is within the same therapeutic category.”

AJMC: Within Independent Health, who made the final call on approving the switch and the efforts around it?

ARQUETTE:

Our Pharmacy and Therapeutics (P & T) committee approved the switch. It’s the pharmacy department’s job to put together the entire case, especially if the plan is to move a product off of the formulary and add another product in its place— something of that magnitude. We have to frame up the entire business and clinical case for the P & T committee so that they understand what we’re trying to do clinically and what we expect to see in terms of safety, efficacy, and cost-effectiveness. We also discuss the impact on members, providers, and the community.

AJMC: With regard to the action plan, what members of the P & T committee were involved in the decision-making process?

ARQUETTE:

The committee is made up of community-based physicians and pharmacists not employed by Independent Health. It’s always great to be able to meet with the people who are in the community and treating patients, because it’s the providers and patients who are impacted by any formulary change. I’m a nonvoting member of the P & T committee. I give clinical presentations, answer questions, and describe what we’re doing in the pharmacy department [and] how we’re managing the pharmacy benefit. However, I don’t vote on any of the decisions.

AJMC: Was there any particular feedback from the P & T committee? Were any specific issues or concerns brought up? Or was it a unanimous vote right from the start?

ARQUETTE:

There was really no opposition. Certainly, the committee members wanted to make sure that these patients were effectively managed and that we were going to do the necessary outreach. Ensuring a seamless transition from Suboxone to ZUBSOLV therapy was critical. Especially with this type of disease state, getting a patient to a point of detox and stabilized on a regimen is extremely difficult and the last thing you want to see is treatment failure and patient relapse. So the P & T members were very focused on making sure that we engaged all the social support and other available resources that the patients would need to make a successful transition.

AJMC: Once you received approval, how was the therapeutic interchange from Suboxone Film to ZUBSOLV Tablet implemented? What steps did Independent Health take to make the therapeutic interchange happen?

ARQUETTE:

Typically when we’re making a change like this, we reach out to the providers first so that they’re aware, because as soon as you start communicating formulary changes to members, they call their providers. We prepared a communication to the providers. We put the clinical information together and framed up why we were making the change. Also, the Orexo team met with some of the high-volume prescribers to give them a heads up. Orexo also offered their resources and said, “We’re here, we can answer any questions, we’re working with the health plan and we want to work with you.” Next, we notified members to make sure they were aware of and understood the change, and then the members started calling. We were committed to ensuring a smooth transition. If prescribers needed lists of their patients or if they needed help with the transition, we were there to help.

AJMC: How did the plan communicate with patients, providers, and pharmacies regarding the interchange? For example, via e-mails, letters, brochures?

ARQUETTE:

We sent prescribers a letter describing what we were doing and included some high-level clinical information and information regarding the product because initially not many prescribers were familiar with ZUBSOLV. For pharmacies, we publish our formulary changes on the provider page of our website. For formulary changes of this magnitude, we’ll send a blast fax to all providers and pharmacies to give them a heads up about what’s coming. Our pharmacists are on the front line and most likely to receive questions about which medications are and are not covered.

We sent letters to members explaining, “This is what you’re being treated with and this is what we’re moving to. These are the steps that you need to take to ensure a seamless transition.” We also tried to reassure them that we were not going to interrupt therapy and that we were working in conjunction with their providers. Later on, additional communications were needed with providers; for example, to explain that although Suboxone and ZUBSOLV are bioequivalent, ZUBSOLV is not available in the same exact strengths as Suboxone due to differences in bioavailability. We attempted to relieve some of their uncertainty and trepidation about the switch.

AJMC: During the implementation phase, what issues, concerns, and/or obstacles did you encounter? How were these addressed? Did any unanticipated issues come up?

ARQUETTE:

We have a clinically based formulary and make changes every year when more cost-effective medications like ZUBSOLV become available, and it seems to go pretty seamlessly. When we make a formulary change, there may be some patients who have a little bit of an issue with it, but generally it’s a smooth transition.

However, this patient population in particular can be a little bit difficult to treat. We didn’t foresee the effect this change was going to have on patients psychologically and their fear of relapsing. People incorrectly thought that we were not covering any product for opioid dependence or that what we were providing coverage of was going to be substandard.

A few physicians wanted us to reverse our decision, but we held firm to our belief that this was a good thing and that we could work through this as long as we both supported the patients and worked together to ease the transition to the new medication. Our health plan has a good reputation with physicians, and working closely with them and making sure they understood the reasons for the change helped relieve the members’ concerns in the end. We kept reinforcing the message with physicians, “There will be positive benefits to the community. It’s going to be a good thing. We just need you to work with us to get us there.”

AJMC: Did you involve case management?

ARQUETTE:

We have a case-management department. I think that there are so many touch points that these patients have: they attend meetings, they go to counseling, they’re engaged with psychosocial support, they’re following up with their doctor. Sometimes our case-management department calls and the patients don’t call back. They don’t want to engage. I think that sometimes they feel that they have enough support.

We did use our case-management team as a resource if we were having difficulty with a member transitioning; for example, if they were experiencing side effects. We worked with our casemanagement department and with the provider to address those concerns. To say, “Well, that’s normal” or “That’s not normal.” We referred them back to their physician when it was appropriate.

AJMC: In the case of this therapeutic interchange, there is a psychological component, as you noted. Other than that, would you say it was similar to other programs? For example, therapeutic interchange involving statins, angiotensin-converting enzyme inhibitors, or beta-blockers?

ARQUETTE:

This was definitely in its own category—it was definitely different than anything we’ve ever done. Initially, there was some misunderstanding regarding what we were doing. With any other formulary decision we’ve made, we’ve never had that type of response from members. The last thing that I would ever want is for it to appear that we were not trying to take care of our members or do what was in their best interest. But we have a very good reputation in our community, we’re very highly regarded, and there were third parties who publically supported our decision.

AJMC: The interchange went into effect on January 1, 2015, so you’ve had nearly a year of experience with the formulary change. What are some of the outcomes of the therapeutic interchange?

ARQUETTE:

In the first couple of months, we received a lot of prior authorization requests for Suboxone. Suboxone was now nonformulary, so providers were going to have to request an authorization to get Suboxone for their patients. We worked with provider offices when patients felt that they were intolerant of the medication. That was very common in the first 2 1/2 to 3 months of the year; then it just started to taper off.

Now, it’s a nonissue. A physician thanked us for making the change, as this has made it much easier for him to address some of his drug-seeking patients. ZUBSOLV is the formulary medication for Independent Health. I have also spoken with patients who prefer ZUBSOLV, and the change had very little impact on them. I think it’s been a tremendous success. There are some patients that we’ve approved Suboxone for, and it may be more of a psychological issue with them, but that is not for me or my team to decide. They feel that they don’t tolerate ZUBSOLV, they don’t feel well on it, they’re not doing well. At the end of the day you have to review each request on a case-by-case basis and determine what’s in the best interest of that patient. We have definitely seen an overall reduction in prescription utilization. An evaluation of our prescription data showed a 24% reduction in utilization (20% in commercial plans and 27% in managed Medicaid plans) and about 18.5% overall unit reduction. From January until the end of October, we saw a net savings of $1 million. That’s impactful. The million dollars saved was due to the reduction in units and the decrease in the number of prescriptions. We don’t have as many prescriptions being filled, and they’re not using as many units of ZUBSOLV as they did of Suboxone. I feel confident that we did a good thing for the community, as well. We may have had a subset of the patient population who were filling these prescriptions, not needing them themselves, and selling them on the street. I’m hoping that we had an impact on this as well.

AJMC: Have you received any feedback from practitioners?

ARQUETTE:

I think physicians sometimes feel their hands are tied. They’re trying to do what’s in the best interest of the patient and practice medicine. I have a personal friend who’s a physician, and he said that he loves the fact that people are not coming in now demanding Suboxone because they know they can’t get it. So it’s now back to the physician to decide whether the patient needs this therapy. It’s just a whole different conversation. Patients know they can’t have it, so it’s taken away the burden of dealing with patients who are demanding something that they may or may not need.

AJMC: Knowing what you know now, would you do anything differently? What recommendations would you offer to other plans that might be looking to implement a similar therapeutic interchange?

ARQUETTE:

I believe that we kicked this off in the fourth quarter of 2014 with a January 1, 2015, effective date. Looking back, I would have started the process sometime in the summer. Also, I would have engaged the prescribers much sooner. I would have met with them, explained to them what we were considering, framed up the entire case, and then asked for their feedback. Also, I would have met with patient advocacy groups to help alleviate the members’ fears along with the prescribers’ fears, so that the transition would have been more seamless. Reaching out to all involved sooner

would have given patients and providers more time to digest the information, ask questions, and be comfortable with the decision we were making. I think the prescribers needed a little bit more time to get the patients into the office, to talk to them about the interchange and provide counseling. Multiple conversations are required in some cases. It’s not going to be a 10- or 15-minute visit. It’s going to be 30 or 45 minutes because more time is needed to talk through all of this. I think maybe being a little bit more proactive like that would have helped a lot.

AJMC: Any final thoughts for others interested in this type of program?

ARQUETTE:

I definitely would do it again. I would just have done it maybe a little bit differently. Had I understood that there was much more to this than just simply switching a patient’s medication from one product to another, then I think it would have been a little bit easier for everybody involved. At the end of the day, I consider it a success and I’m very glad that we did it.

HIGHLIGHTS: IMPACT OF CONVERSION FROM SUBOXONE FILM TO ZUBSOLV TABLETa

-Conversion effective January 1, 2015

-Rationale for conversion:

  • Provide a clinically comparable, cost-effective alternative to Suboxone
  • ŸŸOpportunity to address the potential of abuse and diversion

-24% reduction in utilization of buprenorphine/ naloxone class:

  • ŸŸ20% in commercial plans ŸŸ
  • 27% in managed Medicaid plans
  • $1 million in net savings

a The data presented represent Independent Health’s experience during the time period from January 1, 2015, to September 30, 2015.