New gout treatment guidelines support the use of urate-lowering therapy, but find no place for treating patients to achieve any specific serum urate target – a dichotomy that has some rheumatologists scratching their heads.
Created by the American College of Physicians, the gout diagnosis and treatment guideline doesn’t recommend monitoring physiologic response to urate-lowering therapy or treating to specific serum urate target (Ann Int Med. 2016 Nov 1. doi: 10.7326/M16-0570). Instead, it says patients should be treated according to their symptomatic response – a recommendation that flies in the face of accepted clinical practice.
Dr. Robert McLean
“When we step back and ask the question, ‘Has a randomized, controlled trial looked at this approach?’ The answer is simply no. And we are not willing to take that leap of faith without data.”
Reliance on lower-grade clinical evidence is simply no longer a strong-enough basis for a clinical practice recommendation, Dr. McLean said in an interview. In 2011, the Institute of Medicine raised the bar for guidelines evidence in its report, “Finding What Works in Health Care: Standards for Systematic Reviews.”
That report explicitly states that a clinical guideline cannot be driven by low-grade evidence, including meta-analysis and expert opinion, Dr. McLean said. The Agency for Healthcare Research and Quality National Guideline Clearinghouse incorporated this into its 2013 revision of guidelines acceptance policy: A review must be based on the highest level of evidence – randomized, controlled studies – and not be driven by expert opinion or review articles. Additionally, the literature reviews upon which guidelines are based must be published in a peer-reviewed journal. Guidelines that don’t meet these criteria will no longer be accepted into the clearinghouse.
“The 2012 ACR guidelines didn’t meet that criteria,” he said. “The authors clearly point out in their methodology section where the evidence is weak and admit that 80% of it is low grade. How can you make a guideline that is 80% based on weak evidence? The ACP doesn’t allow us to do that.”
The argument about whether or not to treat to a specific urate target is not simply philosophical, said Dr. McLean, who authored an accompanying editorial (Ann Int Med. 2016 Nov 1. doi: 10.7326/M16-2401). In it, he argued that treating to a prespecified target would certainly help some patients but would probably hurt others.
“Treating to a target necessarily means increasing doses of medication in patients who may be asymptomatic,” he wrote. “Examples exist from other studies using intermediary biomarkers (such as elevated blood pressure or blood glucose level or low hemoglobin level), in which treating to a target resulted in more adverse effects than benefits. Thus, despite the strong biologic appeal of such a strategy and its advocacy by major specialty society guidelines, we judged the strength of evidence for monitoring to be low.”
Dr. Tuhina Neogi
“This paradigm also has not been formally tested in a randomized clinical trial, and there’s no scientific evidence to support that strategy and a lot of evidence to show its harm,” she said in an interview. “We have a large clinical experience about the ineffectiveness of that strategy. Patients eventually develop tophi, joint damage, and functional limitations when their physicians only treat their gout flares using anti-inflammatory therapy without addressing their underlying cause of gout – high uric acid. They are often dismayed and upset when they realize their physician had let their gout get to that point by just treating their gout flares.”
In other important ways, the two documents are complementary. Both put NSAIDs, corticosteroids, and colchicine at the heart of treating acute gout attacks.
According to the ACP guideline, these treatment strategies are all supported by high-level evidence, which was drawn from a review of 28 studies.