Gout is the most common inflammatory arthritis, affecting approximately 9 million Americans. It is a chronic metabolic disease characterized by monosodium urate (MSU) crystal deposition in the joints and elsewhere. Gout causes its major morbidity through acute disabling arthritis flares that represent the most common cause of arthritis visits to US emergency departments; gout can also cause tophi, bone erosions, and a chronic arthropathy with joint damage, and is associated with cardiovascular-metabolic complications. Acute gout flares can be treated effectively with anti-inflammatory medications. When flares are frequent and burdensome enough, urate lowering therapy (ULT) can be administered to reduce the frequency, reduce tophi, and prevent other complications. Using ULT to reduce serum urate (SU) levels below 6.0 mg/dL (below the MSU saturation point) should dissolve MSU crystals, the likely culprit of gout flares, and mitigate other complications. This ?treat to target? serum urate (TTT-SU) approach has been advocated by rheumatologists. However, the majority of gout cases are seen in primary care and many rheumatologists have concerns that primary care management of gout is not aggressive enough, with too high a threshold to initiate ULT, and use of insufficient doses of ULT to achieve the ?target.? Under-treatment of gout may lead to impairments in patient function due to frequent flares and chronic tophaceous arthropathy with joint damage. However, the TTT-SU approach to manage gout is largely based on pathophysiologic rationale, rather than clinical trials. A recent systematic review for the American College of Physicians' (ACP) Clinical Guidelines Committee confirmed the effectiveness of anti-inflammatory medications for gout flares, and effectiveness of ULT for lowering the risk of acute attacks, but acknowledged, ?treatment to a specific target level has not been tested? and ??we remain uncertain about the value of a treat- to-target strategy compared with a strategy of basing treatment intensity on minimizing symptoms.? The ACP gout management guideline neither recommended a specific threshold for the initiation of ULT, nor a specific SU treatment target. The rheumatology community reacted negatively to the ACP guideline, with the main concern being it might worsen the already suboptimal management of gout in primary care. To attempt to resolve this controversy, we convened an NIH-funded meeting in Boston in the Spring of 2018 that included key stakeholders in gout care. The consensus of this meeting was that a comparative effectiveness trial of strategies of gout management would be the best way to resolve the controversy in an evidence-based manner. Thus, our overarching goal is to design a trial that will fill critical evidence gaps and directly inform current practice. In this application, we propose the following aims to plan such a trial: 1) to conduct a Delphi Panel process to determine the optimal design and parameters for the proposed trial. 2) to prepare trial details, including the U01 proposal (which will be submitted during year two of the planning period) with a study protocol, training documents, manual of operating procedures, consent form, and investigator brochure, and perform a mock recruitment.
We will design a trial to answer a fundamental question in gout management by comparing two accepted gout treatment strategies to determine which is most beneficial for gout outcomes and its direct sequelae, as well as associated cardiometabolic and renal outcomes. We will build on our successful NIH R13-funded conference to conduct a Delphi panel process among gout experts, patients, and other key stakeholders, design a clinical trial, and assess its feasibility, which will culminate in submitting a U01 grant. Such evidence and its effective implementation hold promise to improve care and answer a fundamental clinical question.