Challenges in PsA Management
Psoriatic arthritis (PsA) occurs in about 30% of people with psoriasis.1 Jeffrey Stark, MD, spoke with us about the challenges that can arise when treating patients with PsA. Dr Stark is the US head of medical immunology for UCB based in Atlanta, GA.
Jessica Bard: How should patients with PsA be managed?
Dr Stark: PsA is a potentially serious, heterogeneous disease. Although it primarily affects 2 domains—the joints and the skin—it is a chronic, systemic inflammatory condition with many manifestations. It is common, affecting about 0.25% of the US population.2 Specifically, among patients with psoriasis, the lifetime risk of developing PsA may be as high as 40%.2 Other than these 2 main domains of disease leading to arthritis, as well as skin plaque psoriasis, there are many other manifestations of the disease, such as dactylitis and enthesitis.
While over time physicians and health care providers have been delighted to see the treatment landscape for PsA evolve, there are still patients today who, despite the options available to them, experience disability, poor quality of life, residual pain, residual skin manifestations, and so forth. Even now, we are certainly in need of new therapeutic options for these patients. There are a few key principles to approach the management of PsA that are common to all inflammatory diseases. It is important that these patients receive a quick diagnosis and, after diagnosis, receive early and effective therapy. In inflammatory diseases like PsA, there is a window of opportunity during which treatment outcomes can be optimized. And if that window is missed, either because diagnosis is delayed or treatment is delayed, those patients may never achieve the same level of outcomes that they could have, had their diagnosis and treatment been optimized.
Jessica Bard: What would you say are the challenges in the management of PsA?
Dr Stark: Treatments for PsA have come a long way in the last couple of decades, but there are some important challenges that the medical community still aspires to conquer. One of those is a need for a more rapid diagnosis. Having plaque psoriasis, for example, is a significant risk factor for the development of PsA. The medical community needs ways to more consistently and systematically screen patients with psoriasis for potential PsA, so those musculoskeletal manifestations can be detected and managed appropriately and early.
With a heterogeneous disease like PsA, with disease domains that stretch across different organ systems, there is a benefit from collaborative care between diff erent members of the health care community. For example, with PsA, patients may benefit from a close collaborative care model between a dermatologist and a rheumatologist. Although this happens in some academic centers or specialized medical centers, it is something that is difficult to orchestrate in the general medical community. New ways for different specialties to collaborate in patients’ care are certainly important to continue exploring, so these patients achieve the best possible outcomes.
Another important challenge in PsA is how to make informed medication choices. The treatment options for PsA have certainly multiplied over the last few decades, and that leaves medical practitioners with the choice of how to choose the right medication for the right patient. At this point, there are no good tools to predict a response, but that research is underway. Many individuals across the health care community and the scientific establishment, and even in areas of government like the National Institutes of Health, are working to collaborate and shed some light on this question, so the right medication can be chosen for a particular patient from the outset.
Jessica Bard: You mentioned the need for new options in treatment. Can you give us an overview of the BE COMPLETE study, and why it is important?
Dr Stark: The BE COMPLETE study is a study of a molecule in development at UCB called bimekizumab.3 The study was a randomized, multicenter, double-blind, placebo-controlled, parallel-group, phase 3 study that was designed to evaluate the efficacy and safety of bimekizumab for treating active PsA in adults, specifically adults with a history of inadequate response to tumor necrosis factor-α (TNF-α) therapies. TNF-α inhibitors are an established treatment mechanism for PsA, but some patients do not respond to some of the available therapies and need additional options. The BE COMPLETE study was designed specifically to evaluate such a patient population. A total of 400 participants with activePsA were enrolled in the study.
What was exciting was that the BE COMPLETE study met its primary end point of an American College of Rheumatology (ACR) 50 response at week 16. This is a rather stringent end point that goes beyond the traditional ACR 20 threshold that is seen in most PsA clinical trials and aims to establish a higher threshold or higher expectations for what treatment outcomes could look like in clinical trials in the interest of advancing those outcomes for patients in the real world.
In addition to meeting its primary end point, BE COMPLETE also met all its ranked secondary end points intended to capture the range of manifestations or ways in which PsA can impact patients today. Those ranked secondary end points included physical function, skin clearing, physical health status, and low disease activity as measured by the Minimal Disease Activity Index. This is an important measure of disease that can be used in clinical practice and aims to capture some of the heterogeneous manifestations of disease that PsA patients are known to experience.
The BE COMPLETE study is the second phase 3 study with positive results for bimekizumab in active PsA. An earlier study of PsA in biologic-naïve patients met its primary and all ranked secondary end points.4 These results emerging from the bimekizumab PsA clinical program are eagerly anticipated, as clinicians and their patients are continuing to seek options that may more effectively address the many manifestations of the disease.
Jessica Bard: What other medications are in the pipeline to treat PsA?
Dr Stark: While there are some small molecules being explored in this space, few biologics beyond bimekizumab are in development for PsA at this time. There is an opportunity and an interest in the bimekizumab data that can continue to speak to unmet needs.
In addition to bimekizumab, UCB also has an approved treatment for PsA, a medication called certolizumab pegol, which is an anti-TNF therapy, with a different mechanism of action than bimekizumab. As various options are available to patients today and those that may still be in development are being considered, it is important to remember that every patient with PsA is unique. It is a strength of the clinical community to have this multiplicity of options available to choose for their patients who may need different options depending on their responses to therapy and the different manifestations of their disease.
Bimekizumab is part of an ongoing large, heterogeneous clinical program at UCB. There are ongoing clinical programs examining the efficacy and safety of bimekizumab in plaque psoriasis, PsA, ankylosing spondylitis, nonradiographic axial spondyloarthritis, and hidradenitis suppurativa. The data will emerge from the ongoing clinical trials with the goal of understanding the ways in which bimekizumab may be a solution for patients living with many impactful inflammatory diseases.
Jessica Bard: What is next for research in the management of PsA?
Dr Stark: Some great work is being done around management challenges, looking at things like biomarkers and algorithms to help predict response to therapy and inform medication choice for the individual patient. UCB is certainly moving forward with the bimekizumab clinical program. Ultimately, we hope to bring bimekizumab to market as a solution for patients with PsA in the future.
References
1. About psoriatic arthritis. National Psoriasis Foundation. Updated November 24, 2021. Accessed May 31, 2022. https://www.psoriasis.org/about-psoriatic-arthritis
2. Mease PJ, Armstrong AW. Managing patients with psoriatic disease: the diagnosis and pharmacologic treatment of psoriatic arthritis in patients with psoriasis. Drugs. 2014;74(4):423-441. doi:10.1007/s40265-014-0191-y
3. A study to evaluate the effi cacy and safety of bimekizumab in the treatment of subjects with active psoriatic arthritis (BE COMPLETE). US National Library of Medicine. April 1, 2019. Updated March 15, 2022. Accessed May 24, 2022. https://www.clinicaltrials.gov/ct2/show/NCT03896581
4. A study to test the efficacy and safety of bimekizumab in the treatment of subjects with active psoriatic arthritis (BE OPTIMAL). March 29, 2019. Updated May 20, 2022. Accessed May 24, 2022. https://www.clinicaltrials.gov/ct2/show/NCT03895203
