Faculty Bibliography

OBJECTIVE:Disagreement exists between rheumatology and primary care societies regarding gout management. This paper describes a formal process for gathering input from stakeholders in the planning of a trial to compare gout management strategies. METHODS:We recruited patients, nurses, physician assistants, primary care clinicians, and rheumatologists to participate in a modified Delphi panel (mDP) to provide input on design of a trial focused on optimal management for primary care patients with gout. The 16 panelists received a plain-language briefing document that discussed the rationale for the trial, key clinical issues in gout, and aspects of trial design. The panelists also received information and considerations on nine voting questions (VQs), judged to be the key design questions. Cognitive interviews with panelists ensured that the VQs were understood by the range of panelists involved in the mDP. Panelists were asked to score all VQs from 1 (definitely no) to 9 (definitely yes). Two voting rounds were conducted-round 1 by email and round 2 by video conference. RESULTS:The VQs were modified through the cognitive interviews. The round 1 voting resulted in consensus on eight items, with consensus defined as median voting score in the same tercile (1-3, 4-6 or 7-9). Re-voting at the meeting (round 2) reached consensus on the remaining item. CONCLUSION/CONCLUSIONS:An mDP with various stakeholders facilitated consensus on the design of a trial of different management strategies for chronic gout. This method may be useful for designing trials of clinical questions with substantial disagreement across stakeholders.

PURPOSE OF REVIEW/OBJECTIVE:Although gout is a common, well-recognized, and extensively researched rheumatologic disease, it continues to be underappreciated and undertreated. Although the prevalence of gout has been rising over the past several decades, adherence to urate lowering therapy continues to be suboptimal. Recent studies have underscored the potential success of guideline-directed therapy. RECENT FINDINGS/RESULTS:Adherence to gout treatment continues to be suboptimal according to multinational metaanalyses. Moreover, studies measuring adherence are prone to overestimation and each methodologic approach has intrinsic limitations. Adherence may be analyzed from the perspective of patient adherence to taking a medication, or provider adherence to treatment guidelines. In addition to considering traditional risk factors, adherence should be viewed through the lens of healthcare disparities. The RAmP-Up trail and Nottingham Gout Treatment trial demonstrate the success of protocolized gout treatment using existing guidelines for reference. SUMMARY/CONCLUSIONS:Standardized gout treatment protocols should be established for all primary care and specialty practices. Two successful methods of improving adherence include using nonphysician providers to coordinate urate lowering therapy titration and monitoring serum urate. Having more frequent outpatient visits to focus on direct patient care and education has also been successful.

INTRODUCTION/BACKGROUND:Pegloticase is a recombinant PEGylated uricase that converts relatively insoluble urate to highly water-soluble allantoin, which is readily excreted by the kidneys. It is the first and only biologic treatment indicated for refractory or uncontrolled gout. Clinical trials showed a 6-month pegloticase responder rate of 42%, with the non-responder rate largely being attributed to the development of high-titer anti-drug antibodies (ADAs) against pegloticase. Immunomodulation attenuates ADA formation to biologics in a number of autoimmune conditions, but their use with pegloticase for uncontrolled gout is less established. This systematic review examined published cases of refractory gout patients treated with immunomodulation in combination with pegloticase. METHODS:Published cases of immunomodulation with pegloticase were identified in a PubMed search and in abstract databases of major rheumatology society meetings (2012-2020). Duplicate and review articles were excluded, as were those that did not include cases of pegloticase use with immunomodulation. Cases with off-label pegloticase administration schedules were also excluded. Pegloticase response was defined according to each study's specified standard. RESULTS:Ten publications describing 82 cases of pegloticase use in the setting of immunomodulation were identified. Overall pegloticase response rate was 82.9%. Patients co-treated with an individual immunomodulator had the following response rates: methotrexate: 87.5% (35 of 40 patients), mycophenolate mofetil: 86.4% (19 of 22 patients vs. pegloticase monotherapy [placebo]: 40% [4 of 10 patients]), azathioprine: 63.6% (7 of 11 patients), and leflunomide: 66.7% (4 of 6 patients). A single patient was co-treated with cyclosporin and was a responder. The two patients treated with more than one immunomodulator were both responders. CONCLUSION/CONCLUSIONS:Published reports suggest that immunomodulation co-therapy has the potential to markedly improve pegloticase responder rates in patients with uncontrolled gout.

OBJECTIVE:Intra-articular (IA) injections of glucocorticoids (GCs) have been shown to decrease pain, increase mobility, and improve quality of life in patients with osteoarthritis (OA) of the knee. Concerns about cartilage loss with IA GCs have prompted reconsideration of their use in knee OA. This review has three objectives: 1) critically review the clinical, molecular, and structural effects of IA GCs in knee OA; 2) provide a design for a clinical trial aimed at improving our understanding of the long-term consequences of IA GCs; and 3) provide practical guidance on the use of IA GCs in patients with knee OA based on current information. DESIGN:A narrative review of current literature on the use of IA GCs for OA of the knee. RESULTS:Important questions remain to be fully answered with respect to IA GCs, including long-term effects on all aspects of the structural and molecular environment of the knee, and identification of factors that can reliably predict a positive or negative response to IA GCs. CONCLUSIONS:While awaiting results from an appropriately designed study, several provisional statements regarding IA GCs can be put forward: 1) IA GCs appear to be a relatively safe option that is effective in specific patients with symptomatic knee OA; 2) there is no definitive evidence that IA GCs accelerate joint deterioration to an important extent or hastens the requirement for knee replacement; and 3) there are few contraindications to IA GCs and injection-associated complications are rare when IA GCs are delivered with proper technique.

PURPOSE OF REVIEW/OBJECTIVE:Gout is the most common inflammatory arthritis in the USA, affecting about 4% of all adults. The American College of Rheumatology (ACR) released a new guideline in 2020 to help with the management of gout. This guideline serves as an update to the previous set of guidelines which the ACR published in 2012. The purpose of this review is to compare the 2012 ACR gout guidelines to the newly released 2020 ACR gout guidelines. RECENT FINDINGS/RESULTS:There are many similarities between the two guidelines, and also several key differences. The 2020 guidelines assist in the clinical management of gout by healthcare providers. Additionally, the new guidelines utilize newer literature to help create an evidence-based approach to the treatment for gout. We discuss the methodological approach to each guideline (RAND versus GRADE), as well as the final recommendations for gout flare treatment, use of imaging, urate-lowering therapy, lifestyle changes, and genetic testing prior to initiation of allopurinol in each guideline, as well as lingering issues that the 2020 guidelines have not addressed. We dissect both the 2012 and 2020 ACR gout guidelines to summarize the key similarities and differences between the two as well as discuss how the authors came to the recommendations that they did for each set of guidelines.

BACKGROUND:Inflammation is associated with coronary artery disease (CAD) and myocardial infarction (MI). Patients with gout are at increased risk of MI, and colchicine is associated with a reduced risk of MI. The objective of this study was to determine whether colchicine prevents incident development of CAD in patients with gout. METHODS:This retrospective study followed a cohort of male gout patients without known CAD at the time of gout diagnosis in the VA New York Harbor Healthcare System. The association between colchicine use and development of incident CAD, defined as evidence of ischemia or obstructive CAD on stress test or angiography, was determined using an inverse probability weighted (IPW) cox proportional hazard model. RESULTS:Among 178,877 patients, 1,638 met gout criteria, of whom 722 patients without known CAD at baseline (446 colchicine users and 276 non-users) were followed for a median of 96 months [57-117]. A trend toward association between colchicine use and reduced incident CAD was observed but not statistically significant (IPW HR 0.49 [0.23-1.05]). In patients without chronic kidney disease, colchicine use was associated with a lower rate of incident CAD (interaction p=0.005, IPW HR 0.31 [0.14-0.70]). Colchicine was also associated with a lower rate of the composite of incident CAD and MI (IPW HR 0.37 [0.16-0.83]). CONCLUSIONS:In male patients with gout and no known CAD, a trend of reduced incident CAD was observed with colchicine use that was not statistically significant. Larger, prospective studies will be required to definitively assess the primary prevention benefit of colchicine.

Background/Purpose: Spinal gout is reported as a rare event, presenting as acute back pain, neuropathy, and spinal compression. Diagnosis is commonly based on identification of a mass, followed by tissue confirmation of monosodium urate (MSU) deposition. It is likely that many more cases of gout involve the spine asymptomatically or with non-specific or under-recognized symptoms.
Method(s): Using dual-energy CT (DECT), we are determining the prevalence/extent of MSU deposition in the lumbosacral spines of patients with gout vs without gout, and with tophaceous vs non-tophaceous gout. We are recruiting 25 controls, 25 non-tophaceous and 25 tophaceous gout patients, 50-80 years old. Exclusion criteria include known CPPD disease, RA, spondyloarthropathy or active spinal malignancy. All gout subjects meet ACR classification criteria and have entry serum urate (sU) of >6.8 mg/dL, or sU >6.0 mg/dL on ULT for < 6 months. Demographics, gout history, Aberdeen back pain scale, sU, ESR, and CRP are collected. Subjects undergo DECT of the lumbosacral spine to assess for MSU deposition and osteoarthritic changes.
Result(s): 61 subjects are enrolled to date (25 control, 24 non-tophaceous and 12 tophaceous gout). Control and gout (all pooled) subjects have similar mean age in years (controls, 61.8+/-3.8 vs gout, 64.1+/-7.32, p=0.15), but differ in BMI (controls, 28.3+/-6.5 kg/m 2 vs gout, 32.35+/-6.9 kg/m 2, p=0.02) and creatinine (controls, 1.0+/-0.2 mg/dL vs gout, 1.5+/-0.7 mg/dL, p< 0.05). Mean sU and ESR are higher in gout subjects (sU-controls, 5.3+/-1 mg/dL vs gout, 8.7+/-1.7 mg/dL, p< 0.05; ESR-controls, 13.7+/-13.8 mm/h vs gout, 25.3+/-18.3 mm/h, p< 0.05). Using default threshold settings for MSU visualization, greater MSU deposition is observed in the spine of gout patients (controls, 2.2+/-1.2 cm 3 vs gout, 10.8+/-32.2 cm 3, p=0.18; Fig 1). When a single gout outlier with excessively high sU and spinal MSU is excluded, spinal MSU deposition between controls and gout patients becomes significant (controls, 2.2+/-1.2 cm 3 vs gout, 5.6+/-7.8 cm 3, p=0.04). Reanalysis of several scans using narrower threshold settings to limit possible artifact confirms increased MSU signal among gout patients. Although many subjects in each group do not have excessive MSU deposition, deposition is more common in both gout groups (Fig 2). Thus far, MSU deposition is not different between non-tophaceous and tophaceous gout patients (non-tophaceous, 12.3+/-2.92 cm 3 vs tophaceous, 7.9+/-3.2 cm 3, p = 0.7). No subject demonstrated a frank spinal tophus. Gout patients report higher back pain scores (controls, 5.7+/-8.3, vs gout, 11.8+/-14.3, p=0.06). Across all groups deposition is greater in patients with higher sU.
Conclusion(s): Based on preliminary results, gout patients have higher inflammatory markers, more spinal MSU deposition, and increased back pain versus controls. Preliminary results with more stringent DECT threshold settings suggests these differences are not artifact, but analysis is ongoing. These data suggest that non-tophaceous MSU deposition in the spine occurs in a subset of gout patients, is associated with sU level, and may be associated with low back pain

BACKGROUND:Patients with aortic stenosis are nearly twice as likely to have a diagnosis of gout compared with individuals without aortic valve disease. METHODS:, and/or decrease in left ventricular ejection fraction due to aortic stenosis. RESULTS:/year [-0.16, -0.01], p=0.09); annualized change in peak velocity and mean gradient did not differ between groups. CONCLUSIONS:Progression to severe aortic stenosis was more frequent in patients with gout versus those without gout supporting the hypothesis that gout is a risk factor for aortic stenosis.