Bimekizumab and Patient-Reported Outcomes and Work Productivity in Patients With Psoriatic Arthritis | Written Recap

Psoriatic arthritis (PsA) remains a complex, highly impactful disease that necessitates a treatment strategy extending beyond simple joint counts and skin clearance. In this Managed Healthcare Executive Between the Lines video series, Eingun James Song, M.D., a dermatologist and director of clinical research at Frontier Dermatology in Seattle, and Philip Mease, M.D., a rheumatologist at Providence Swedish Medical Center, which is also in Seattle, discussed the results of the pivotal phase 3 BE-OPTIMUM and BE-COMPLETE trials for bimekizumab.

Their conversation highlighted why the drug’s distinct mechanism of action, which targets both interleukin (IL)-17A and IL-17F, offers a crucial therapeutic addition, particularly for hard-to-treat symptoms such as pain and fatigue.

Understanding the disease burden

PsA is a multi-clinical domain disease that Mease described as a “full orchestra in fortissimo mode,” with various sections — the joints, skin and axial spine — all active at once. The disease encompasses not only psoriasis of the skin and nails but also arthritis, enthesitis (inflammation where ligaments and tendons attach to the bone), dactylitis (inflammation of the fingers and toes) and axial involvement (inflammation affecting the spine).

For the patient, this multifaceted inflammation translates directly into reduced quality of life, experienced as pain, stiffness and profound fatigue. This chronic burden is frequently compounded by comorbidities such as depression, cardiovascular disease and fibromyalgia.

“I think we can all agree that psoriatic arthritis is not just a matter of reducing a tender swollen joint count or improving a PASI [Psoriasis Area and Severity Index] score,” Song noted. “There are various different facets of this disease, and ultimately, at the end of the day, it's how does this disease affect a patient's quality of life and their ability to function? And that may matter even more.”

The acute symptoms bringing patients to the clinic are often joint and insertion site pain, which can severely limit function. Mease offered the example of a violinist in the Seattle Symphony who could not play due to active
dactylitis in a finger that made them unable to play. Stiffness can affect patients, particularly in the morning and make them feel like "the Tin Man in 'The Wizard of Oz,' waiting for Dorothy to come along with the oil can," he said. Another common complaint is fatigue, which contributes significantly to a sense of depression and inability to "exercise their full capacity" at work or home.

Evolution of treatment

Treatment for PsA has evolved significantly since the early 1980s, when traditional agents like gold injections and methotrexate were the standard of care; Mease characterized them as "quite patchy and quite inadequate."

The advent of the biologic era, beginning with tumor necrosis factor (TNF) inhibitors, expanded the therapeutic armamentarium by targeting key pathophysiologic drivers like TNF, IL-17 and IL-23. Although these advancements have been monumental, there remains an unmet need, Song explained, as many patients still never reach a state of low disease activity, the drugs lose efficacy over time, or treatments are discontinued due to adverse events. This ongoing challenge highlights the need for new mechanisms that offer true differentiation.

Dual mechanism of action

Bimekizumab represents an advance within the IL-17 class by uniquely inhibiting both IL-17A and IL-17F. The latest research indicates that inhibiting both IL-17A and IL-17F provides a more comprehensive blockade of the IL-17 inflammatory stimulus, distinguishing it from existing IL-17A inhibitors such as secukinumab and ixekizumab.

“What we end up recognizing when we do translational studies after getting these treatments is that there's crossover,” Mease said. “When you inhibit TNF, you get some inhibition of IL-17 going on and vice versa. There is a greater ability to reduce the inflammatory drive coming from TNF and IL-17 when using these medications.”

The biological rationale for this dual approach is strong: IL-17F is estimated to be 30 to 50 times more abundant in the skin and synovium compared with IL-17A, and it can activate the IL-17 receptor A independently of IL-17A. This difference suggests that patients who have not responded well to prior TNF-alpha or IL-17A inhibitors still have the potential for a favorable response with bimekizumab, a phenomenon already observed in clinical practice and case series.

Trial design and results

The two phase 3 trials — BE-OPTIMUM and BE-COMPLETE — were multicenter, double-blind and placebo-controlled for 16 weeks, with an active reference arm of treatment with Humira (adalimumab) used in BE-OPTIMUM. The primary end point for both was a 50% or greater improvement in the American College of Rheumatology criteria at week 16.

The BE-OPTIMUM trial included patients who had not been treated with biologics, while BE-COMPLETE included patients who either had an inadequate response to a TNF-alpha inhibitor or were intolerant of it.

The BE-OPTIMUM and BE-COMPLETE data showed minimal difference in efficacy outcomes, such as ACR50 response rates and minimal disease activity achievement, between the patients who were biologic-naïve and those who had an inadequate response to a TNF inhibitor.

The baseline patient demographics were reflective of a typical practice population: patients in their 50s, a significant degree of obesity (average body mass index just under 30), a long disease duration (six to 10 years) and high conventional synthetic disease-modifying antirheumatic drug use (nearly 70%, mostly methotrexate).

When their conversation turned to efficacy, Song and Mease focused on patient-reported outcomes. Baseline pain scores were high (approximately 60 out of 100 on a visual analog scale), indicating a highly impactful daily burden. By week 16, bimekizumab-treated patients showed a highly significant improvement compared with placebo, with many achieving thresholds of major improvement (50% reduction in pain). Patients who switched from placebo to bimekizumab “catch up” and experience a significant improvement in pain, Mease said. “We know that, unfortunately, a lot of these patients with chronic disorders that are in pain have to turn to pain medications, and that sets them up for a lot of other downstream consequences.”

Patients usually name fatigue as the second-most bothersome symptom after pain. Although clinicians often don't ask about it, fatigue can, of course, affect a person's ability to work. Patients taking bimekizumab showed significant improvement in fatigue, Mease noted. Critically, more than half of the treated patients achieved a minimal clinically important difference in fatigue.

Improvements in general health-related quality of life were observed across the Psoriatic Arthritis Impact of Disease 12-Item Questionnaire, the Psoriatic Arthritis Quality of Life Measure and the Bath Ankylosing Spondylitis Disease Activity Index.

Addressing unmet need

Mease stressed the importance of continuously bringing forward new agents to move the needle toward low disease activity or remission and to tackle critical symptoms such as pain and fatigue.

Song said that the cost of undertreating PsA is often overlooked. Patients who remain inadequately controlled not only experience symptoms and discomfort from the disease but also incur substantial long-term financial consequences.

“These patients represent, if untreated, a real burden to the healthcare network,” said Mease. “I think that one of the key things is that paying for these medications and getting such improvement in disease activity is beneficial to payers as well.”