Gout Flare Prophylaxis & Therapy Use in Patients With CKD

Gout is often linked with other comorbidities that are clustered within the metabolic syndrome, but it is also frequently associated with renal impairment. “Chronic kidney disease (CKD) is a highly prevalent comorbidity in patients with gout,” says Angelo Gaffo, MD. Research shows that slightly more than 70% of Americans with gout have stage 2 or higher CKD, and approximately 20% have stage 3 or higher CKD (Table). Gout is also highly prevalent in patients with preexisting CKD.

A Glaring Need for Evidence-Based Guidance

The degree of renal impairment—especially in advanced CKD—plays an important role in treatment decisions when managing patients with gout. Current guidelines list colchicine, NSAIDs, and parenteral/oral glucocorticoids as preferred first-line treatments for gout flares, but the use of these options as prophylaxis in people with CKD is not always straightforward. These therapies may require dose adjustments and close patient monitoring for efficacy and safety. “Healthcare professionals caring for patients with gout lack evidence-based guidance on the efficacy and safety of drugs that are commonly used to treat gout flares and for flare prophylaxis in patients with CKD,” Dr. Gaffo says.

For a study published in Arthritis Research & Therapy, Dr. Gaffo and colleagues explored the best currently available evidence on the efficacy and safety of gout flare prophylaxis and therapy in patients with stage 3, 4, and 5 CKD. “Our goal was to evaluate the existing literature on the topic to identify key areas for future research,” says Dr. Gaffo. Specifically, the investigators reviewed studies that provided efficacy and/or safety analyses for patients diagnosed with gout with stage 3 or higher CKD who were exposed to gout flare prophylaxis or therapy. These treatments included colchicine, interleukin-1 (IL-1) inhibitors (eg, anakinra, canakinumab), NSAIDs, and glucocorticoids.

Insufficient Data in Patients With Gout & Advanced CKD

The study team reviewed 33 studies with efficacy and/or safety analyses stratified by renal function. “The most important finding from our research was the confirmation that we lack data on the efficacy and safety of drugs used to treat gout flares,” Dr. Gaffo says. “We have even less data for gout flare prophylaxis in patients with CKD. Almost all clinical trials excluded patients with advanced CKD, which precludes the development of evidence-based recommendations to treat this patient population.” Data were also lacking regarding efficacy and safety outcomes of gout flare prophylaxis and therapy use when stratified by renal function.

The dearth of high-quality data reporting in this high-risk comorbid population is concerning. “Future gout studies should deliberately include patients with different stages of CKD,” says Dr. Gaffo. “In addition, clinicians treating patients with gout and CKD should actively encourage their patients to participate in clinical studies.”

 

Addressing Gout Flare & Advanced CKD Research Deficiencies

Dr. Gaffo and colleagues noted that future gout research should aim to profile drug safety by comparing patients with and without CKD whenever possible. “Our study has identified multiple deficiencies that need to be studied further,” Dr. Gaffo says. “Some of these areas include analyses of the safety, effectiveness, and dosing of colchicine in CKD, the duration of glucocorticoid use in CKD, and the safety of IL-1 inhibitors in CKD. Furthermore, we need research that investigates the need for dosing adjustments in the context of CKD. Future studies must also seek to determine if gout flare prophylaxis is needed in all patients with CKD starting urate-lowering therapies.”

The study team added that it is important to have an accurate and validated definition and assessment of gout flare in all clinical studies. By incorporating a standardized definition of a gout flare, clinicians can fairly and efficiently compare outcomes across studies of different options for gout flare prophylaxis and therapy. Ideally, future research will also place a greater emphasis on stratifying renal function. “By addressing these key steps, results from future gout flare prophylaxis and treatment studies can better guide clinicians in their management of gout flares and prophylaxis in patients with advanced CKD,” says Dr. Gaffo.