Psoriatic arthritis treatment guidelines have evolved significantly in the past decade, reflecting a growing recognition of the limitations of traditional disease-modifying antirheumatic drugs (DMARDs) and the superior efficacy of biologic therapies. Dr. Saakshi Khattri, a rheumatologist at the Icahn School of Medicine at Mount Sinai, has observed this shift firsthand in her clinical practice in New York City, where she now routinely initiates biologic therapy for patients with active psoriatic arthritis without requiring a prior trial of methotrexate or other conventional synthetic DMARDs. This approach marks a departure from earlier treatment paradigms, which often mandated a stepwise progression from oral medications to injectable biologics only after failure of first-line agents. The change is driven by accumulating evidence that biologics not only provide more consistent disease control but also address the complex nature of psoriatic arthritis, which affects joints and skin.
The adoption of biologics as first-line therapy is not limited to academic medical centers or urban practices. Dr. Philip Mease, a rheumatologist at Swedish Medical Center and the University of Washington, has noted that this trend extends to community-based clinics and smaller healthcare systems, where patients frequently encounter difficulties with methotrexate. These challenges include gastrointestinal side effects, liver toxicity, and variable efficacy, particularly in patients with more severe or rapidly progressing disease. Methotrexate, while effective for some forms of inflammatory arthritis, often fails to achieve adequate control of both joint and skin symptoms in psoriatic arthritis, leading to prolonged periods of active disease and irreversible joint damage. The latest ACR guidelines now support using a biologic ahead of methotrexate.
Access and approval challenges
Despite the growing consensus among rheumatologists and updated guidelines, securing insurance approval for biologics as first-line therapy remains a persistent obstacle. Insurers often adhere to outdated step-therapy protocols, requiring patients to fail methotrexate or another conventional DMARD before approving coverage for a biologic. Dr. Khattri has developed a pragmatic workaround in her practice to circumvent these barriers. When faced with a denial for a biologic based on psoriatic arthritis diagnosis alone, she leverages the patient’s concurrent psoriasis diagnosis to justify the prescription. Since methotrexate is not considered the standard of care for moderate to severe psoriasis—where biologics are frequently first-line—this approach allows her to bypass initial resistance from payers. The strategy shows the disconnect between clinical guidelines and insurance policies, which often lag behind advances in medical evidence and fail to account for the overlapping manifestations of psoriatic disease.
The BE BOLD trial design
The BE BOLD trial represents a significant advancement in the comparative evaluation of biologic therapies for psoriatic arthritis. As the first head-to-head study to directly compare bimekizumab, a dual interleukin (IL)-17A and IL-17F inhibitor, with risankizumab, an IL-23 inhibitor, the trial aims to provide clarity on the relative efficacy and safety of these two mechanistically distinct agents. The Phase 3b study, presented at the 2024 European Congress of Rheumatology (EULAR) meeting in London, enrolled 553 adult participants across multiple centers. The inclusion criteria were designed to reflect real-world patient populations, encompassing both biologic-naive individuals and those who had previously failed a tumor necrosis factor (TNF) inhibitor. This dual eligibility ensures that the trial’s findings are applicable to a broad spectrum of patients, including those with refractory disease who may have limited treatment options.
Related: User Account Blocked by Moderators
Participants were randomized in a 1:1 ratio to receive either bimekizumab or risankizumab at their respective labeled dosing regimens. The trial’s primary endpoint was a joint-centric ACR50 response, a more stringent measure of clinical improvement than the traditionally used ACR20. The ACR50 threshold requires a 50% reduction in tender and swollen joint counts, along with a 50% improvement in at least three of five additional domains, including patient and physician global assessments, pain, and physical function. This raised standard reflects a growing emphasis on achieving deeper levels of disease control, which is associated with better long-term outcomes, including reduced joint damage and improved quality of life. Secondary endpoints further expanded the trial’s scope, incorporating minimal disease activity (MDA), a composite measure that assesses multiple dimensions of psoriatic arthritis, including skin involvement, enthesitis, and dactylitis. The inclusion of ACR50 combined with PASI100—a 100% reduction in psoriasis severity—highlights the trial’s focus on addressing both joint and skin manifestations, which are often inadequately controlled by conventional therapies.
An additional innovation in the BE BOLD trial was the inclusion of an early ACR50 readout at week four, a timeframe that aligns with the rapid onset of action observed with some biologic agents. This early assessment provides valuable insights into the speed of response, which is a critical factor for patients with highly active disease who may be at risk of irreversible joint damage. The trial also evaluated Disease Activity in Psoriatic Arthritis (DAPSA) low disease activity or remission, a validated tool that quantifies disease activity based on joint counts, acute-phase reactants, and patient-reported outcomes. By incorporating these diverse endpoints, the BE BOLD trial offers a full evaluation of treatment efficacy, moving beyond simplistic measures of improvement to capture the complex impact of psoriatic arthritis on patients’ lives.
Dr. Khattri emphasized that the patient population in the BE BOLD trial closely mirrors the individuals she treats in her practice, where many present with both joint and skin involvement and have either not responded to prior therapies or experienced intolerable side effects. The trial’s design, particularly its use of ACR50 as the primary endpoint and the inclusion of an early response assessment, provides a framework for setting realistic expectations with patients. Historically, clinical trials in psoriatic arthritis have relied on ACR20, a threshold that may not fully capture the degree of improvement needed to achieve meaningful disease control. By raising the bar to ACR50, the BE BOLD trial reflects a broader shift in the field toward more ambitious treatment targets, which are increasingly recognized as necessary to prevent long-term disability and improve patient-reported outcomes. The next phase of the discussion will examine the trial’s results, including how bimekizumab and risankizumab performed across these rigorous efficacy and safety measures.
