Pegloticase Treatment Associated with Bone Remodeling in Gout

Kenneth Saag, MD

Credit: The Rheumatologist

Treatment with pegloticase was linked to concomitant bone remodeling within a 1-year span, although reductions slowed or stopped following pegloticase discontinuation.¹

As previous data involving dual-energy CT (DECT) during pegloticase and methotrexate concomitant therapy are scarce, a team of investigators enrolled a cohort of patients from a randomized controlled trial to confirm bone-erosion remodeling following monosodium urate (MSU) depletion with pegloticase in patients with uncontrolled gout.¹

Pegloticase, prescribed to lower serum urate (SU) in this patient population, is sometimes combined with methotrexate to increase the SU-lowering response rate while decreasing the risk of infusion reaction.¹

In an interview with HCPLive, Kenneth Saag, MD, director of Clinical Immunology and Rheumatology at the University of Alabama at Birmingham, discusses the clinical significance of these data.

HCPLive: What inspired your team to analyze MSU deposition in patients with gout receiving pegloticase?

Kenneth Saag, MD: The deposition of MSU in bones and soft tissues is the hallmark of gout. Its presence in those areas ultimately results in damage or loss of mobility and deformity and functional limitations to people with gout. So, understanding the level of data and the response to the treatment is indicative of the effectiveness of therapy and gout.

HCPLive: How does the reduction in MSU deposition contribute to bone healing and remodeling and these patients?

Saag: First, it's important to point out that when you have deposition of uric acid crystals around bones there can be damage to the bones or changes where the bones literally get eaten away by the inflammatory reaction. And that can cause disfigurement, deformity, and can lead to loss of mobility. What we've learned is that when gout is effectively treated, and those crystals are resorbed over time, their burden is significantly reduced. Although some of the damage may persist, there's also the potential for healing and ultimately some restoration of normal function around the joint.

HCPLive: Did the results surprise you?

Saag: I think we've come to expect that uricase is, in essence, the ingredient that humans are missing and the reason that we get gout. We don't break down uric acid as many animal species do and we don't easily excrete it. Providing this externally rapidly reduces the uric acid in the blood and ultimately leads to its resorption from soft tissues and around bones. Understanding that better over time using newer imaging modalities is really state-of-the-art in trying to get a sense of how effectively we can control really bad gout.

HCPLive: What implications do these results have for both clinical practice and patient care?

Saag: It further confirms that, for patients with refractory gout, the use of a drug like pegloticase is remarkably effective in lowering serum urate from around the bones and then the soft tissues, which can ultimately result in some healing around those areas when we use newer imaging modalities like DECT, which is just a way to actually visualize the deposition of monosodium urate around the joints.

HCPLive: In your opinion, how do these findings fit into the broader landscape of gout treatment and management strategies?

Saag: Most rheumatologists have gained some familiarity and comfort with the use of pegloticase in their very severe gout patients and this is further confirmatory that this therapy, when used selectively in patients with bad gout, not only will reduces serum urate to often unmeasurable levels initially, but can ultimately result in some improvement around the soft tissues and in the bones where there's been damage from the gout.

HCPLive: Were there any notable challenges or limitations encountered during your trial analysis process?

Saag: Not really. For most patients, it's generally well tolerated and has a rather fast onset of action that leads ultimately, over a relatively short period of time—much, much shorter than with any other existing urate lowering therapies—to improvement in in gout and a subsequent reduction in flares in the soft tissues and the bones.

HCPLive: What are the next steps for your team?

Saag: There will undoubtedly be additional studies to try to better characterize longer term effects. Clinical trials are often insufficiently large, long enough, and practiced often enough to apply to patients that we seek and the people that get included. But I think we need more population-based data to look at how we can even more effectively utilize a drug like pegloticase in the real world.

HCPLive: Is there anything else that you would like our audience to know?

Saag: Gout is the most common form of inflammatory arthritis and the most common type of inflammatory arthritis in men—up to 10% of men in their later years develop gout— but it's often viewed by many as kind of a nuisance condition. However, it can cause severe chronic arthritis and it has associations with other serious medical conditions like hypertension, chronic kidney disease, and cardiovascular disease. So, we're glad that there's increasing attention being paid to it and new therapies and existing therapies are being studied further.

Disclosures: Saag is a funded investigator and consultant of Amgen and lgchemnis.

References

1. ^{Dalbeth N, Botson J, Saag K, et al. Examination of monosodium urate crystal depletion and bone erosion remodeling during pegloticase treatment in patients with uncontrolled gout: exploratory dual-energy computed tomography findings from MIRROR RCT. Joint Bone Spine. Published online March 4, 2024. doi:10.1016/j.jbspin.2024.105715}