Philip Mease, MD, Discusses Head-to-Head BE BOLD Clinical Trial

Early this month, UCB announced the commencement of the BE BOLD study, a pivotal phase 3b clinical trial aimed at comparing the efficacy of bimekizumab (Bimzelx; UCB) against risankizumab (Skyrizi; AbbVie) in treating adults with active psoriatic arthritis (PsA). Following this news, Dermatology Times spoke with lead investigator of the BE BOLD study, Philip Mease, MD, director of Rheumatology Research at Providence Swedish Medical Center.

Transcript

Philip Mease: Hi, I'm Philip Mease. I'm director of Rheumatology research at Providence Swedish Medical Center, and I conduct clinical practice at Seattle rheumatology associates.

Dermatology Times: What implications might the results of head-to-head studies such as this have on clinical practice?

Mease: We have more medications that have become and are becoming available for the treatment of PsA. Many of the medicines are quite successful in being able to achieve low disease activity or remission, which is our treatment goal in patients with PsA. Not only to achieve low disease activity or remission in musculoskeletal elements, such as the joints, the enthesis, the spine, but also in the skin and nails. PsA is a really impactful disease to have, because not only is the patient troubled by this cosmetically and uncomfortable psoriasis that's covering that'simpacting their skin and very visible in in the world, but alsothey've got the double whammy of having musculoskeletal pain and physical dysfunction as a result of it. Having treatments available that can render this kind of benefit, that actually both of these drugs can yield, then that's a great boon for patients, clinicians, the workforce where the patients are working, the family members who are with these patients. There is a tendency for medications that have been used historically to wear off in their effect over time. That's why we continually need new medications. There have been very few actual head-to-head studies in psoriatic arthritis. Head-to-head studies are important because they are the gold standard for telling us the relative effectiveness as well as relative safety of drugs for treating the different clinical medical domains of PsA that I've just previously listed. Part of the reason head-to-head studies aren't done is that it's expensive. You need lots and lots of patients in order to be able to show statistical separation between 1 drug and another, but it is so invaluable for clinicians to be able to have this information to teach their patients andmake choices of treatments.We do have a number of head-to-head studies and psoriasis, just the skin aspect.For example, bimekizumab has been tested head-to-head successfully, meaning it has bested TNF inhibitor, IL-12/23 inhibitor and an IL-17A inhibitor. As you know, bimxizumab is an IL-17A and F inhibitor. Its a unique new mechanism exploiting the fact that itwe've learned that not only is IL-17A, but also IL-17F important in inflammation. We have that historical record with those other mechanisms, but we don't have any trial that compares bimekizumab with an IL-23 inhibitor. That's what this BE BOLD study is about. It's to to see whether or notthere's a difference between the effect of bimekizumab and the effect of risankizumab, 1 of the IL-23 inhibitors in PsA. So important and could be a landmark study and will really help guide dermatologists and rheumatologists as they go about making choices for their patients.

DT: How does using ACR50 as the primary endpoint aid in assessing the effectiveness of these therapies?

Mease: ACR50 is a higher threshold of response than has been the primary endpoint in many studies. Historically, we've looked at the ACR20 - a 20% improvement in multiple different aspects of the clinical disease. ACR50 is much closer to getting to a state of low disease activity, which is more satisfactory for patients. It’s appropriate target of treatment, a higher hurdle to get to, but appropriate, I think, at this point in time. To really try to show a difference between the 2 agents, it's focused a little bit more on the articulate musculoskeletal aspects of the disease. The skin response will, of course, be measured as a secondary measure, but we're really focusing on how well do these 2 drugs work in the in the arthritis component, as well as patient global to achieve success.

DT: Do you believe this paired with secondary endpoints such as PASI100 will lead to a fuller understanding of efficacy?

Mease: In PsA trials, we do measure all of these things. We measure the arthritis response, the enthesitis response, seeing whether there's resolution of pain and the anti-inflammation. We measure dactylitis, which is a swelling of a whole digit. We measure skin and nail changes. We measure improvements in fatigue. One that has become a favorite of ours, the minimal disease activity criteria we employ this in our clinic, in every patient where there are 7 items, including an assessment of the joints, the skin, the enthesis, patient global, patient pain and if the patient has achieved very high thresholds. If they achieve5 of the 7 items that make up this criteria, then they're in a state of quite a high rate of satisfaction for treatment response. It's associated with other good outcomes, like improvement of quality of life, better work productivity, achievement of inhibition of structural damage progression, as measured by x-ray. So really good target.That will be measured and what we've seen with bimekizumab historically in the placebo-controlled trials, is high rates of achievement of MDA in the 45% range at primary endpoint.

DT: How do you believe the different mechanisms of action between these drugs will compare?

Mease: We'll be looking at each of the domains and seeing whether or not there's a statistical differentiation between the 2 different mechanisms.We know that IL-17A and F inhibitors tend to work pretty quickly.So it is anticipated that at the week 16 primary endpoint, it would not be a surprise if the effect was better in the IL-17A and F inhibitor compared to the IL-23 mechanism. We tend to see a slightly lower rates of response early on, but then ultimately, with time, the IL-23 inhibitors get to be at a better place. It'd be really fascinating, not only to see the results at the primary endpoint of week 16, but at other time points as well.

DT: How might the results of this study affect existing treatment guidelines?

Mease: Every 4 years or so, the various associations that come out with treatment guidelines, such as GRAPPA (Group for Research and Assessment of Psoriasis and Psoriatic Arthritis), which I'm part of, or the EULAR (European Alliance of Associations for Rheumatology) guidelines, I've also been part of that set of treatment recommendations. There's a new ACR (American College of Rheumatology) evaluation of PSA treatment guidelines coming out. We would expect that the results of this trial, when available, will be worked into those guidelines. I think all both of these drugs are seen quite favorably in the guidelines, and this will just give us a little bit more guidance about relative effectiveness of these 2 mechanisms.

DT: Are there any other notes about the study you would like to add?
Mease: We're so appreciative of the ability to use a number of different drugs that have been in development and approved and new drugs that are being developed. This is a complex disease. It's a very impactful disease. We know that we need new therapies in order to keep patients in a state of low disease activity.I’m just highly appreciative.Almost 27 years ago was the first trial that I ran an independent study using a TNF inhibitor known as etanercept, that really kicked off the testing of biologic medications. We've seen a sea change in our ability to get good results and really be able to treat patients. I'm very grateful for this.

[This transcript has been edited for clarity.]