Progress continues on the development of new formulations of medicines to treat opioid use disorder. One extended release formulation of buprenorphine, Sublocade, was approved for use in the U.S. in 2018, and another, Brixadi, could get final approval later this year. Work on naltrexone implants in a variety of formulations continues.
Strategies for delivery of OUD medications is evolving as well, with the COVID-19 pandemic creating a new, recent challenge in the process.
At the upcoming virtual National Conference on Addiction Disorders, Marc Fishman, MD, medical director for Maryland Treatment Centers and a faculty member at the Johns Hopkins University School of Medicine, will discuss advancements in medications for OUD, including what’s new and what’s still to come. Ahead of that session, he spoke with Addiction Professional about the state of OUD medications and medication delivery strategies, meeting patients “upstream,” and the impact COVID-19 is having on advancements in the field.
Editor’s note: This interview has been edited for length and clarity.
With regards to new medications and new medication delivery strategies that you are seeing in the pipeline, what are some key differences or improvements that differentiate these developments from what has been implemented up to this point?
The background here is that we are very lucky in our field to have such high effect-sized, FDA-approved medications for OUD. The effectiveness of these medicines, their wide availability, their increasingly wide dissemination and adoption is really very beneficial to patients and has been part of the early flattening of the overdose death curve we were starting to see. That said, there are limitations. These are not curative medicines. As good as these medicines are, we still have considerable barriers to reaching more people, and those include relatively disappointing retention and adherence in the broader population of patients with OUD. Even at their best—and these are the best medicines we have for the treatment of OUD, and we don’t even have many medicines for other specific substances—even in the best boutique research, we’re looking at a benchmark of about 50% retention at six months. Now, I’m not saying that that’s so much worse than with other chronic illnesses. We have the same issues with difficulties with retention and adherence with hypertension and diabetes, and on and on. Given that overdose deaths and this ongoing epidemic is still raging, that’s a major barrier.
The question, then, is to ask what we can do to improve on what’s already good. How do we get beyond that with retention? How do we make medicines better? How do we make delivery of medicines better, with new ways of organizing and strategies for engaging and retaining patients? And are there boosters, whether those medication boosters, augmentation strategies, additional medications that prevent relapse over and above these medicines, or behavioral strategies that can be layered on to increase effectiveness?
I have organized them into three broad categories. One is new formulations of these medicines and how there are new pharma products coming to market that improve upon the tried and true and some dosing strategies around those new products. Topic No. 2 is delivery strategies, enhancements in the ways of getting these medicines to patients. As good as the medicines are, they don’t work unless you get them into the hands of patients. So, what are some ways of getting people into care, meeting people upstream, perhaps in the cascade of care initiating points along the way, with ways of delivering the medication that support engagement, initiation, retention and adherence. The third topic is strategies for augmentation. What else can you do to improve medicines’ effectiveness? Are there medicines or other treatments to add? Treatments of co-morbid substances? People don’t only use opioids, they use other substances as well, and these FDA-approved medicines for the treatment of OUD don’t have a direct pharmacological effect on other substances of misuse.
On the topic of meeting patients upstream, are you seeing more efforts specifically around delivery of treatment in non-traditional settings?
Exactly right. It takes many steps for patients to get to the specialty care system, and of course, we’re still going to need lots of concentrated specialty and subspecialty work in that arena. But there are so many touchpoints upstream before patients make it to subspecialty care, and we have not traditionally done a good job of doing case detection and engagement and trying to get people into care at those upstream touchpoints where there are lots of people who present and there may be an opportunity.
Those kinds of places include emergency departments. I’m certainly not the first person to make that point. People come to emergency departments for opioid overdoses and soft tissue infections or opioids and other traumatic injuries. We put a Band-Aid on them and save their lives, which is very laudable, but what about treating the underlying opioid addiction? Hospitals are where people are admitted for the medical consequences of opioid use disorder, and those medical consequences are appropriately addressed, but maybe the opioid use disorder is neither identified or, if it is identified, isn’t treated. So, it’s initiating medicines from the non-addiction hospital episode of care. Incarceration is another upstream point. The criminal justice system’s overlap with OUD is well known. It’s enormous. That’s increasingly recognized as a vital touchpoint in which people who have battled opioid use disorder are not cured just by being locked up. Not only can people still use while they’re incarcerated, but just because they’ve been abstinent by confinement does not treatment make. They are at an enormously high risk of relapse upon release.
What impact has the COVID-19 pandemic had on all this? Is it slowing the development of new medications and formulations and delivery strategies?
There are a bunch of different ways COVID is making an impact. It’s obviously very early, so we don’t have huge amounts of data, but it’s very important to try to make projections not only about what’s happened during this crisis, which is going to continue for quite some time, but also what happens beyond the crisis when we eventually get a vaccine and move beyond the pandemic. One of the ways delivery strategies have been impacted is with the broad-based shift to telehealth with the relaxation of previous restrictions on HIPAA complexity and compliance and on other limitations on reimbursement including technical details like the Ryan Haight Act, which requires that people initiating buprenorphine have at least one in-person visit with a practitioner prior to initiating treatment with controlled substances like buprenorphine. With the relaxation of those and other regulatory barriers, in some ways, we’ve seen a plus in terms of lowering barriers for vulnerable populations to initiation of care and engagement in care and to be able to continue in care. Practitioners are being less restrictive with supplies of medicines, and that applies to the relaxation of restrictions around OTP methadone programs with more take-homes and the like. It will be interesting to see what continues past the pandemic and what doesn’t, but we’re learning a lot.
I do think on the other hand, there is a negative side. You lose a lot in terms of therapeutic alliance when you aren’t able to meet face-to-face with a person. Whereas lots of people are talking about a reduction of engagement barriers with the continuation of existing episodes of care where patients who are migrating from in-person care to telehealth care, there is still a major barrier for new episodes of care. This COVID pandemic increases stress for everybody and creates difficulties that are well known. Increased stress usually produces increased rates of use, decreased rates of behavior change, increased levels of ambivalence, and decreased rates of motivation as people are troubled with chaos throughout their lives. As that tipping point of ambivalence is troublesome to people, it isn’t clear whether pre-stabilized patients who are first putting their toe in the waters of care for OUD are as easily as able to access care through telehealth without in-person services. We’ve seen this, for example, with a dramatic reduction in entries and capacity for residential care, which is a vital part of the treatment continuum. That has been a major stressor on the system for patient care capacity.