Post-Psych Congress Recap: Drs Chepke and Goldberg Discuss New Real-World Evidence on Aripiprazole Monohydrate Every-Two-Month Formulation in Adults Living With Bipolar I Disorder - the REAL-BD Study

Drs Craig Chepke and Joseph Goldberg review new primary and secondary findings from
REAL-BD, a real-world, long-term study on use of an every-2-month long-acting injectable in bipolar I disorder.

View the Real-World, Long-Term Impact of Transitioning From Oral Antipsychotics or Aripiprazole Once-Monthly to Aripiprazole 2-Month Ready-To-Use in Adults Diagnosed with Bipolar I Disorder: The REAL-BD Study poster here.

Craig Chepke, MD: I'm Craig Chepke. I was recently at Psych Congress Annual meeting in New Orleans presenting a number of sessions, but I tried to take in and learn as much as I could as well. Unfortunately, like every congress, there were more interesting sessions and posters than I could even get to. But, one topic I wanted to spend more time on was long-acting injectables, LAIs, in bipolar I disorder. I saw that my colleague Dr Joe Goldberg was first author on 2 posters with new real-world data from the REAL-BD study, so I asked him to jump on a quick call and walk me through what I missed.

Hey Joe—it’s great to see you. Thanks for making time.

Joseph Goldberg, MD: Good to see you too, Craig. And happy to catch up.

Chepke: So, I saw the abstracts and had a peek at the posters, but I didn't get a chance to dig into the full results. Before we get to the findings, can you remind me what the question the REAL-BD study was designed to answer?

Goldberg: Well, the practical question was straightforward: what happens in clinical practice when adults living with bipolar I disorder transition from oral antipsychotics or aripiprazole monohydrate once-monthly 400 mg, that’s AOM 400, to aripiprazole monohydrate 2-month ready-to-use 960 mg LAI, that’s Ari every-2-month formulation?

Chepke: Yeah, that's what caught my attention. In maintenance treatment, we're trying to prevent recurrent mood episodes and support long-term clinical stability, and adherence, as you know, can be a challenge with daily oral medications. A longer-interval LAI changes the treatment routine, and while we have clinical trial data on Ari every-2-month formulation, real-world outcomes after that transition are really interesting.

Goldberg: Exactly. Ari every-2-month formulation is an aripiprazole LAI given once every 2 months. What’s been missing were real-world clinical outcome data describing the impact on people living with bipolar I disorder after that transition. REAL-BD was designed to help fill that evidence gap.

Chepke: Yeah, that’s great. So, how did you look at that?

Goldberg: REAL-BD was a retrospective, non-interventional, multicenter pre-post chart review. We looked at 72 adults living with bipolar I disorder who had been on either any oral antipsychotic, except clozapine, or on AOM 400 for at least a year before the index date,And that was defined as the date of initiation of Ari every-2-month formulation. Then for each patient, we compared the 12 months before the transition to Ari every-2-month formulation, the pre-index period, with the 12 months after, the post-index period. And the primary endpoint was the proportion of patients with inpatient psychiatric hospitalization due to any mood episode.

Chepke: Oh, okay, so a mirror-image study, where each patient essentially served as their own reference.

Goldberg: Right. And most of the cohort—67 of 72 people living with bipolar I disorder—transitioned from an oral antipsychotic; 5 transitioned from AOM 400. That context matters when you interpret the overall findings.

Chepke: And then the primary outcome was psychiatric hospitalization, right? Tell me about those results.

Goldberg: Yes, so in the 12 months before Ari every-2-month formulation, 13 of 72 people living with bipolar I disorder in the study, that’s 18.1%, had a hospitalization, and in the 12 months after transition, none did. That's an 18.1-percentage-point pre-post difference.

Chepke: Wow! I mean, to me, that’s the kind of result that jumps off the poster. Hospitalization is a high-impact outcome in bipolar I disorder, so seeing that difference over a full year is really notable to me.

Goldberg: It’s an encouraging real-world signal.

Chepke: Yeah, and I want to point out the value here is understanding what was observed in practice over the year after people living with bipolar I disorder transitioned to Ari every-2-month formulation.

So, the primary endpoint is clear. What else from the poster can inform us about the maintenance of clinical stability and overall round out the clinical picture?

Goldberg: So, a few things. All-cause hospitalization decreased from 23.6% pre-index to 2.8% post-index. Reported suicidal ideation was lower post-index. Any reported suicidal ideation went from 47.2% pre-index to 26.4% post-index, and active suicidal ideation went from 27.8% to 4.2%. Passive suicidal ideation decreased numerically from 34.7% to 23.6%, but that comparison was not statistically significant. 

Chepke: Got it. So, one thing that caught my eye in the abstract was the data on low clinical worsening and discontinuation rates. Can you walk me through that real quick?

Goldberg: Sure, so during the 12-month post-index period, 4 people living with bipolar I disorder in the study, that’s 5.6%, met the definition of clinical worsening, and 1 patient, that’s 1.4%, had an unscheduled psychiatric visit.

Over the post-index year, 11 people living with bipolar I disorder in the study, that’s 15.3%, discontinued Ari every-2-month formulation; loss to follow-up was the most common reason for that. None discontinued because of lack of efficacy. 

Chepke: These are really interesting findings, Joe, but just remember, we do need to be careful about what we can conclude.

Goldberg: Right. So, with no concurrent comparator, this retrospective pre-post study can’t establish causality. Also, suicidal ideation assessments may have varied across sites, and also there was a higher enrollment of study participants at 1 site, which may reduce generalizability of the findings.

Chepke: Yeah, and the takeaway for me is that REAL-BD is a useful real-world look at what happened over a year after transitioning to Ari every-2-month formulation, particularly those hospitalization findings.

Goldberg: Yes. These findings support the feasibility of transition in clinical practice and add real-world evidence to the long-term maintenance discussion.

Chepke: Well, thanks so much for the chat, Joe and for walking me through the primary and secondary findings. I’d really love to catch up again on the second poster—the exploratory analyses looking at things like healthcare resource utilization and concomitant psychotropic medications after transition to Ari every-2-month formulation.

Goldberg: Absolutely. There's a lot in that second poster that's worth unpacking.

Chepke: Awesome. I’m looking forward to it.

Craig Chepke, MD

Dr Craig Chepke is a board-certified psychiatrist in clinical practice as the medical director of Excel Psychiatric Associates in Huntersville, North Carolina. He serves as an adjunct associate professor of psychiatry for the Atrium Health Psychiatry Residency Program and is the chief medical officer of Psych Congress. As part of an interdisciplinary treatment team in his practice, he employs a person-centered care model to tailor treatments to each individual's needs, integrating traditional pharmacotherapy with psychotherapeutic and physical health and wellness interventions. His clinical and academic interests include serious mental illness, movement disorders, ADHD, and sleep medicine. Dr Chepke has been recognized as a distinguished fellow of the American Psychiatric Association and is a recipient of the National Alliance on Mental Illness Exemplary Psychiatrist Award.

Joseph Goldberg, MD

Dr Joseph Goldberg is a clinical professor of psychiatry at the Icahn School of Medicine at Mount Sinai. He is also the immediate-past president of the American Society of Clinical Psychopharmacology and deputy editor-in-chief of the Journal of Clinical Psychiatry. Dr Goldberg attended medical school at Northwestern University. He completed his residency and chief residency in psychiatry, as well as a fellowship in psychopharmacology, at the Payne Whitney Clinic, New York Presbyterian Hospital. He later served there as faculty and was the site principal investigator at Weill-Cornell Medical Center for the NIMH STEP-BD program. He has published over 260 peer-reviewed papers on bipolar disorder, as well as 5 books on bipolar disorder and psychopharmacology. Dr Goldberg is a distinguished life fellow of the American Psychiatric Association and has been listed for many years in “Best Doctors in America” and Castle Connolly's "America's Top Doctors."