When it comes to treating patients with chronic diseases, we know that one size doesn’t fit all. A regimen that works for one patient may not work as well for another. Like many rheumatologists, solving the puzzle to find answers for each patient is a favorite part of my job. And a key piece to each patient puzzle is reviewing maturing bodies of data, scientific guidelines, and new insights collected from evolving clinical practice.
Gout is a particular focus in my practice in Alaska. It’s a challenging, misunderstood disease because patients often don’t seek care unless they’re experiencing pain. But in between flares, we know from decades of research that the consequences of gout persist. Gout is not just pain and the damage we see in the joints; it also has acute and chronic inflammatory impacts as well as exacerbates comorbidities. The consequences of gout warrant ongoing, thoughtful disease management. This is especially the case in uncontrolled gout, a severe form of gout in which patients do not respond to oral urate-lowering therapies.
The uncontrolled gout patient population has very few treatment options to address the challenges associated with the disease. When the biologic agent pegloticase was approved in 2010, we were armed with a new option that could effectively reduce serum uric acid levels, allowing us to proactively control the impact of the condition in a way that was not previously possible.
Despite being an important advancement for uncontrolled gout patients, some patients developed anti-drug antibodies in response to pegloticase, preventing them from gaining the full benefit of therapy. So, with other rheumatology specialists, I wondered whether adding an immunomodulatory treatment could improve the patient response rate. Rheumatologists often use immunomodulators like methotrexate in combination with biologics for other conditions, and we’ve seen success in reducing the immune reaction so that patients can remain on treatment. After we started this co-treatment approach, we noticed a significant difference. Month-over-month, we could see that our patients were experiencing improved outcomes, including remaining on treatment longer and fewer infusion reactions.
Following multiple case series investigating the co-administration of these two therapies, we launched an open-label trial, and then a randomized controlled trial that completed in 2021, ultimately validating the approach. The primary endpoint of the randomized controlled trial evaluated data at Month 6, but provided a look at data through Month 12.
These 12-month results offered striking insights to inform how we think about treating uncontrolled gout. Patients in the trial not only maintained progress with low serum uric acid levels through Month 12, but we saw evidence of continued improvements in tophaceous deposits through exams and imaging, indicating this longer duration might confer greater benefit. Perhaps more importantly, we observed strong tolerability and safety outcomes.
These outcomes got us thinking about the typical course of pegloticase therapy for people with uncontrolled gout and how we can help more patients reach the goal of controlled serum uric acid levels and a meaningful reduction in tophaceous deposits. Physicians should be encouraged to consider the appropriate length of therapy for each individual, whether it be 6 months, 12 months, or somewhere in between.
In the context of patient care, the findings add more to our toolbox for how we as rheumatologists can continue to solve the puzzle for each patient, and the importance for us as physicians to follow new data to learn more about how we treat chronic disease.
John K. Botson M.D., R.Ph., C.C.D.
John K. Botson M.D., R.Ph., C.C.D., president, Alaska Rheumatology Alliance and rheumatologist, Orthopedic Physicians Alaska.