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Objective: To compare the performance of the 2016 preliminary gout remission definition and a simplified gout remission definition in a clinical trial of nurse-led gout care., Methods: Data from a 2-year parallel arm, non-blinded, randomised controlled trial of 517 community-derived people with gout were analyzed. Participants were assigned 1:1 to receive nurse-led care or general practitioner usual care. Remission was defined using the 2016 preliminary gout remission definition and a simplified gout remission definition without patient reported outcomes. Binary logistic regression was used to compare intervention groups. General linear models were used to compare Gout Impact Scale (GIS) scores between those in remission and those not in remission using either definition., Results: Participants in the nurse-led care group were more likely to achieve remission using either definition; at Year 2 the odds ratio was 7.92 [95 % CI 4.86-12.92] using the 2016 preliminary definition and 11.88 [95 % CI 7.49-18.84] using the simplified definition. For all participants, the 2016 preliminary definition was fulfilled by 9.9 % at Year 1 and 28.4 % at Year 2, p < 0.001 and the simplified definition was fulfilled by 17.6 % at Year 1 and 42.7 % at Year 2, p < 0.001. People in remission using either definition had better gout outcomes assessed using the GIS, including greater control over their gout., Conclusion: Both definitions discriminated between the intervention groups and showed high construct validity. The simplified definition identified more people as being in gout remission at Year 1 and Year 2. The simplified definition is a feasible and valid option for defining gout remission., Competing Interests: Declaration of competing interest Nicola Dalbeth has received consulting or speaker fees from AstraZeneca, Dyve Biosciences, Horizon, Selecta, Arthrosi, JW Pharmaceutical Corporation, PK Med, LG Chem, JPI, PTC Therapeutics, Protalix, outside the submitted work. Lisa Stamp has received royalties from Up-to-Date and consulting fees from Pharmac NZ. Aliya Sarmanova was affiliated with the Nottingham University at the time of the study conduct and is currently affiliated with Roche Diagnostics International, Clinical Development and Medical Affairs. The other authors have no conflicting interests to report., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The 'treat-to target serum urate strategy' when using urate-lowering therapy has been recommended by most specialist rheumatology societies for many years. An alternative "treat-to-avoid-symptoms" in gout has been suggested, albeit without a clear definition of what this means and how it might be implemented in clinical trials or clinical practice. This has hampered efforts to design clinical trials that compare the "treat-to-target [urate]" and "treat-to-avoid-symptoms" strategies in the long-term management of gout. In this review we consider the rationale for the treat-to-target urate strategy when using urate-lowering therapy, potential definitions of a "treat-to-avoid-symptoms" strategy, or perhaps what is not "treat-to-avoid-symptoms", and approaches that might address this uncertainty., Competing Interests: Declaration of competing interest LS reports Research Funding from the New Zealand Health Research Council and consulting fees from Pharmac outside the submitted work. ND- has received consulting fees, speaker fees or grants from AstraZeneca, Novartis, Dyve Biosciences, Horizon, Selecta, Arthrosi, JW Pharmaceutical Corporation, PK Med, LG Chem, JPI, PTC Therapeutics, Protalix, Unlocked Labs, Hikma outside the submitted work., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Rheumatoid arthritis associated interstitial lung disease (RA-ILD), is an important extra-articular manifestation of rheumatoid arthritis (RA). The frequency, risk factors, and prognosis of RA-ILD are incompletely understood., Aims: To determine the prevalence and incidence, clinical characteristics and risk factors for development, and outcomes of persons with RA-ILD in the population of the Canterbury District Health Board (CDHB) catchment area., Methods: Individuals aged ≥ 18 years with RA, resident in the CDHB catchment area between 1 January 2006 and 31 December 2008 (Period One), and 1 January 2011 to 31 December 2013 (Period Two) were identified by medical record review and followed until 30 June 2019. Individuals with RA-ILD as defined by pre-specified criteria were identified. The association between demographic and clinical characteristics and RA-ILD development and mortality was examined using Cox-proportional hazards models., Results: The prevalence of RA-ILD per 100,000 was 10.97 (95 % CI 7.53,14.42) for Period One, and 14.74 (95 % CI 10.84,18.63) for Period Two. Among individuals evaluated for risk factors for RA-ILD development, the estimated cumulative incidence of ILD at 10 years was 4.47 % (95 % CI 3.14, 6.14). After adjusting for age, rheumatoid factor positivity (HR 3.73, 95 % CI, 1.32,10.56), extra-articular manifestations other than RA-ILD (HR 4.48, 95 % CI 2.36,8.48), and subcutaneous rheumatoid nodules (HR 4.66, 95 % CI 2.34, 9.26) were associated with increased risk of developing RA-ILD. The standardised mortality ratio for RA-ILD was 3.90 (95 % CI 2.55,5.72) compared to the general population. Extent of ILD on CT chest was associated with mortality (HR for >20% vs. < 20 % 4.47, 95 % CI 1.67,11.96)., Conclusions: Clinically evident RA-ILD occurred in approximately 5 % of individuals with RA. Mortality was increased almost fourfold compared to the general population. Radiologic extent was the most important prognostic factor., Competing Interests: Declaration of Competing Interest LKS has received grants or contracts to from Health Research Council of New Zealand paid to their institution, royalties or licenses from UpToDate, and payments for participation on a data safety monitoring board or advisory Board from Pharmac paid to them and their institution. DB has received a scholarship grant from University of Otago funded by Arthritis New Zealand. ELM has received grants from Abbvie Inc, royalties or licenses from UpToDate, consulting fees from Beohringer-Ingelheim GmBH, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Beohringer-Ingelheim GmBH, Participation on a Data Safety Monitoring Board or Advisory Board for Horizon Therapeutics and National Institute of Health, Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid for The American College of Rheumatology., (Copyright © 2023. Published by Elsevier Inc.)

Background: Dual energy computed tomography (DECT) allows direct visualization of monosodium urate crystal deposition in gout. However, DECT urate volume data are often highly skewed (mostly small volumes with the remainder considerably larger), making statistical analyses challenging in longitudinal research. The aim of this study was to explore the ability of various analysis methods to normalise DECT urate volume data and determine change in DECT urate volumes over time., Methods: Simulated datasets containing baseline and year 1 DECT urate volumes for 100 people with gout were created from two randomised controlled trials. Five methods were used to transform the DECT urate volume data prior to analysis: log-transformation, Box-Cox transformation, log(X-(min(X)-1)) transformation; inverse hyperbolic sine transformation, and rank order. Linear regression analyses were undertaken to determine the change in DECT urate volume between baseline and year 1. Cohen's d were calculated as a measure of effect size for each data treatment method. These analyses were then tested in a validation clinical trial dataset containing baseline and year 1 DECT urate volumes from 91 people with gout., Results: No data treatment method successfully normalised the distribution of DECT urate volumes. For both simulated and validation data sets, significant reductions in DECT urate volumes were observed between baseline and Year 1 across all data treatment methods and there were no significant differences in Cohen's d effect sizes., Conclusions: Normalising highly skewed DECT urate volume data is challenging. Adopting commonly used transformation techniques may not significantly improve the ability to determine differences in measures of central tendency when comparing the change in DECT urate volumes over time., Competing Interests: Declaration of Competing Interest Lisa Stamp reports grants or contracts from Health Research Council of New Zealand, personal royalties or licenses from UptoDate, and consulting fees from Pharmac. Nicola Dalbeth reports grants or contracts from Health Research Council of New Zealand and Novotech, personal consulting fees from AstraZeneca, Dyve Biosciences, Horizon, Selecta, Arthrosi, JW Pharmaceutical Corporation, PK Med, PTC Therapeutics, Protalix, Cello Health, JPI, Unlocked Labs, and LG, payment or honoraria from Novartis and Hikma. The other authors declare no conflicts of interest., (Copyright © 2023. Published by Elsevier Inc.)

Objective: The selection and reporting of core outcome measures in clinical trials is essential for patients, researchers, and healthcare providers for clinical research to have an impact on healthcare. In this systematic scoping review, we aimed to quantify the extent to which gout clinical trials are collecting and reporting data in accordance with the core outcome domains from Outcome Measures in Rheumatology (OMERACT) published in 2009 applicable for both acute and chronic trials and evaluate the reporting according to the core domains before and after the 2009 OMERACT endorsement., Methods: We searched multiple databases PubMed, EMBASE, the Cochrane Library including the Cochrane Central Register of Controlled Trials (CENTRAL), and Cochrane Database of Systematic Reviews (CDSR) and www., Clinicaltrials: gov for randomized controlled trials (RCTs) allocating people with gout versus an active pharmacological gout treatment or a control comparator (no date limitation). We extracted the data in accordance with the core outcome sets, focusing individually on core outcome domains and the core outcome measurements for acute and chronic trials, respectively. In this study 'Acute trials' reflect studies that describe interventions for short term management of gout flares, and 'chronic trials' describe interventions for long-term urate lowering therapy in the management of gout., Results: From 8,522 records identified in the database search, 134 full text papers were reviewed, and 71 trials were included, of which 36 were acute and 35 were chronic. Only 3 of 36 (8%) acute trials reported all five core domains and none of the 35 included chronic trials reported all 7 core domains. In the acute trials, twenty-seven unique measurement instruments across the 5 core domains were identified. For chronic trials there were 31 unique measurement instruments used across the 7 core domains. Serum urate was reported in 100% of the chronic trials and gout flares in 80%. However, other core domains were reported in <30% of chronic trials. In particular the patient-important domains such as HR-QOL, patient global assessment and activity limitations were rarely reported. A broad variety of different measurement instruments were used to assess each endorsed core domain, a minority of trials used the OMERACT endorsed instruments. For acute trials, the number reporting on all core domains was consistently low and no change was detected before and after the endorsement of the core domains in 2009. None of the included chronic trials reported on all 7 endorsed core domains at any time., Conclusion: In this study we found a low adherence with the intended endorsed (i.e., core) outcome domains for acute and chronic gout studies which represents a poor uptake of the global OMERACT efforts for the minimum of what should be measured in clinical trials. In addition, there is a significant variation in how the OMERACT endorsed outcome domains have been measured. This systematic review demonstrates the need for continuous encouragement among gout researchers to adhere to OMERACT core domains as well as further guidance on outcome measurements reporting., Registration: Prospero: CRD42019151316., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Rheumatoid arthritis associated interstitial lung disease (RA-ILD) is associated with high levels of morbidity and mortality. The primary aim of this systematic review was to determine the duration of survival, from time of diagnosis of RA-ILD., Methods: Medline (Ovid), Embase (OVID), CINAHL (EBSCO), PubMed, and the Cochrane Library were searched for studies that reported duration of survival from time of diagnosis of RA-ILD. Risk of bias of included studies was assessed based upon 4 domains of the Quality In Prognosis Studies tool. Results for median survival were presented by tabulation and discussed qualitatively. Meta-analysis of cumulative mortality at 1 year, >1y to ≤3 years, >3 years to ≤5 years, and >5 years to≤ 10 years was undertaken, for total RA-ILD population, and according to ILD pattern., Results: 78 studies were included. Median survival for the total RA-ILD population ranged from 2 to 14 years. Pooled estimates for cumulative percentage mortality up to 1 year were 9.0% (95% CI 6.1, 12.5, I 2 88.9%), >1 to ≤3 years 21.4% (17.3, 25.9, I 2 85.7%), >3 to ≤ 5 years 30.2% (24.8, 35.9, I 2 87.7%), and > 5 to ≤ 10 years 49.1% (40.6, 57.7 I 2 85.0%). Heterogeneity was high. Only 15 studies were rated as low risk of bias in all 4 domains assessed., Conclusion: This review summarises the high mortality of RA-ILD, however the strength of conclusions that can be made is limited by the heterogeneity of the available studies, due to methodological and clinical factors. Further studies are needed to better understand the natural history of this condition., Competing Interests: Declaration of Competing Interest LKS has received grants or contracts to from Health Research Council of New Zealand paid to their institution, royalties or licenses from UpToDate, and consulting fees from Pharmac paid to them and their institution. ELM has received royalties or licenses from UpToDate, consulting fees from Beohringer-Ingelheim and Alvotech Inc, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Practice Point Communications/Simply Speaking, Beohringer-Ingelheim, Novartis, Participation on a Data Safety Monitoring Board or Advisory Board for Horizon Therapeutics and National Institute of Health USA, Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid The American College of Rheumatology., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Serum urate (SU) is the most common primary efficacy outcome in trials of urate-lowering therapies for gout. Despite this, it is not formally considered a validated surrogate outcome. In this paper we will outline the definitions of biomarkers and surrogate outcome measures, respectively as well as the available frameworks and challenges in the assessment of the validity of serum urate as a surrogate in gout (i.e. a reasonable replacement for gout symptoms)., Competing Interests: Declaration of Competing Interest MBM: No conflicts declared, RC: No conflicts declared, JAS: Has received consultant fees from Crealta/Horizon, Medisys, Fidia, PK Med, Two labs Inc., Adept Field Solutions, Clinical Care options, Clearview healthcare partners, Putnam associates, Focus forward, Navigant consulting, Spherix, MedIQ, Jupiter Life Science, UBM LLC, Trio Health, Medscape, WebMD, and Practice Point communications; and the National Institutes of Health and the American College of Rheumatology. JAS owns stock options in TPT Global Tech, Vaxart pharmaceuticals and Charlotte's Web Holdings, Inc. JAS previously owned stock options in Amarin, Viking and Moderna pharmaceuticals. JAS is on the speaker's bureau of Simply Speaking. JAS is a member of the executive of Outcomes Measures in Rheumatology (OMERACT), an organization that develops outcome measures in rheumatology and receives arms-length funding from 12 companies. JAS serves on the FDA Arthritis Advisory Committee. JAS is the chair of the Veterans Affairs Rheumatology Field Advisory Committee. JAS is the editor and the Criteria subcommittee. Director of the University of Alabama at Birmingham (UAB) Cochrane Musculoskeletal Group Satellite Center on Network Meta-analysis. JAS previously served as a member of the following committees: member, the American College of Rheumatology's (ACR) Annual Meeting Planning Committee (AMPC) and Quality of Care Committees, the Chair of the ACR Meet-the-Professor, Workshop and Study Group Subcommittee and the co-chair of the ACR Criteria and Response, ND: Reports consulting fees from AstraZeneca, Dyve BioSciences, Selecta, Horizon, and Arthrosi, speaker fees from Abbvie and Janssen, and research grants from Amgen and AstraZeneca, outside the submitted work. ORCID: 0000-0003-3485-0006, KS: Reports he is an Investigator for Horizon, Sobi, LG, Dyve and consulting fees from Horizon, WJT: No conflicts declared ORCID 0000-0001-6075-8479, TN: No conflicts declared. ORCID 000-002-9515-1711, MK: No conflicts declared ORCID 0000-0002-6445-8526, BMP: No conflicts declared, GMM: No conflicts declared, BJS: Is the senior Methodologist. ORCID 0000-0002-7686-2585, CDT: No conflicts declared. ORCID 0000-0001-6275-7699, SKT: No conflicts declared, RG: personal fees from Pfizer, Cornerstones, Jannsen, and Novartis. AA: No conflicts declared, ML: No conflicts declared, AG: No conflicts declared ORCID 0000-0001-7365-7212, LSS: Serves as a consultant to Horizon Therapeutics. He serves on the Executive of OMERACT and is Chair of the Finance Committee of OMERACT and Co-Chair of It's Business Advisory Committee., AN: No conflicts declared, SMN: No conflicts declared, ML: No conflicts declared, PT: No conflicts declared ORCID 00000-0001-5062-0556, LKS: No conflicts declared ORCID 0000-0003-0138-2912, (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: Although calcium pyrophosphate deposition (CPPD) is common, there are no published outcome domains or validated measurement instruments for CPPD studies. In this paper, we describe the framework for development of the Outcome Measures in Rheumatology (OMERACT) CPPD Core Domain Sets., Methods: The OMERACT CPPD working group performed a scoping literature review and qualitative interview study. Generated outcomes were presented at the 2020 OMERACT CPPD virtual Special Interest Group (SIG) meeting with discussion focused on whether different core domain sets should be developed for different calcium pyrophosphate deposition (CPPD) clinical presentations and how the future CPPD Core Domain Set may overlap with already established osteoarthritis (OA) domains. These discussions informed development of a future work plan for development of the OMERACT CPPD Core Domain Sets., Findings: Domains identified from a scoping review of 112 studies and a qualitative interview study of 36 people (28 patients with CPPD, 7 health care professionals, one stakeholder) were mapped to core areas of OMERACT Filter 2.1. The majority of SIG participants agreed there was need to develop separate core domain sets for "short term" and "long term" studies of CPPD. Although CPPD + OA is common and core domain sets for OA have been established, participants agreed that existing OA core domain sets should not influence the development of OMERACT core domain sets for CPPD. Prioritization exercises (using Delphi methodology) will consider 40 potential domains for short term studies of CPPD and 47 potential domains for long term studies of CPPD., Conclusion: Separate OMERACT CPPD Core Domain Sets will be developed for "short term" studies for an individual flare of acute CPP crystal arthritis and for "long term" studies that may include participants with any clinical presentation of CPPD (acute CPP crystal arthritis, chronic CPP crystal inflammatory arthritis, and/or CPPD + OA)., Competing Interests: Declaration of Competing Interest KC reports a research fellowship grant from Arthritis Australia. RC is a member of the Technical Advisory Group of OMERACT. JAS has received consultant fees from Crealta/Horizon, Medisys, Fidia, PK Med, Two labs Inc, Adept Field Solutions, Clinical Care options, Clearview healthcare partners, Putnam associates, Focus forward, Navigant consulting, Spherix, MedIQ, Jupiter Life Science, UBM LLC, Trio Health, Medscape, WebMD, and Practice Point communications; and the National Institutes of Health and the American College of Rheumatology. JAS owns stock options in TPT Global Tech, Vaxart pharmaceuticals and Charlotte's Web Holdings, Inc. JAS previously owned stock options in Amarin, Viking and Moderna pharmaceuticals. JAS is on the speaker's bureau of Simply Speaking. JAS is a member of the executive of OMERACT. DG has a private equity holding in Charlotte's Web Holdings, Inc. ND reports grants and personal fees from AstraZeneca, grants from Amgen, personal fees from Dyve, personal fees from Hengrui, personal fees from Selecta, personal fees from Horizon, personal fees from Abbvie, personal fees from Pfizer, personal fees from Janssen, personal fees from Arthrosi, outside the submitted work. AA and SKT have received consultant fees from NGM Biopharmaceuticals. FB has received personal consultant fees from Horizon Therapeutics. OMERACT, an organization that develops outcome measures in rheumatology, receives arms-length funding from 8 companies. The other authors have no disclosures., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Rationale & Objective: The association between hyperuricemia and urolithiasis has been previously reported. However, this association is based on observational data, which are prone to residual confounding. The aim of this work was to use Mendelian randomization (MR) to evaluate if this relationship represents a causal effect of hyperuricemia., Study Design: MR analysis using 2 approaches: 2-stage MR and 2-sample MR., Setting & Participants: Participants aged 40-69 years from the UK Biobank Resource., Exposure: Serum urate., Outcome: Urolithiasis., Analytical Approach: An observational analysis testing for an association between serum urate level and urolithiasis was performed using logistic regression. For MR analyses, serum urate-associated single-nucleotide polymorphisms, identified from genome-wide association data, were used as instrumental variables for serum urate. In the 2-stage MR analysis, a weighted genetic urate score was calculated from the instrumental variables, and a control function estimation model was fit. In the 2-sample MR analysis, multiple-instrument MR via the inverse-variance weighted method was performed., Results: Individual-level data were available for 359,827 participants, of whom 6,398 (1.8%) reported urolithiasis. In the observational analysis, serum urate was positively associated with urolithiasis in an unadjusted analysis (odds ratio [OR], 1.47 [95% CI, 1.42-1.51]); however, after adjustment for relevant confounders, no association was observed (OR, 1.03 [95% CI, 0.99-1.08]). In the 2-stage MR analysis, no significant causal effect of serum urate level on urolithiasis was observed in the unadjusted (OR, 0.93 [95% CI, 0.81-1.08]) or adjusted (OR, 0.94 [95% CI, 0.80-1.09]) models. In the 2-sample MR analysis, multiple-instrument MR did not indicate a causal effect of serum urate on urolithiasis., Limitations: Stone composition and urinalysis data, including urine pH, were not available for this study., Conclusions: Our analyses do not support a causal effect of serum urate level on urolithiasis. The association between serum urate level and urolithiasis reported in observational studies is likely due to residual confounding., (Copyright © 2021 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: The potential effect of cigarette smoking on levels of serum urate and risk of gout has been considered by a large number of studies, either as the primary variable of interest or as a covariate., Methods: Here we systematically review the published evidence relating to the relationship of smoking with serum urate, hyperuricaemia, and gout., Results: Many studies have reported that smoking reduces serum urate, however, the evidence has not been conclusive with other studies pointing to the opposite or no effect. It has also been suggested that smoking reduces the risk of gout, although there is some evidence to contradict this finding., Conclusion: A consensus has yet to be reached as to the effect of smoking on serum urate levels and the risk of gout., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Higher fructose intake has been associated with hyperuricaemia and gout. Some individuals malabsorb fructose in the small intestine. The aims of this study were to determine the rate of fructose malabsorption and the effects of gout and fructose malabsorption on serum urate in people with and without gout., Methods: A total of 100 people with gout (cases) were age and gender matched with one control without gout. After a low fructose diet, fructose malabsorption was measured using a hydrogen and methane breath test with a 35g fructose load. In a subgroup of 35 cases and 35 controls, serum urate response to the fructose load over 240 minutes was measured., Results: There was no significant difference in the rate of fructose malabsorption between cases and controls (48% vs. 52%; p = 0.67). Cases had a significantly lower mean (SEM) serum urate cumulative incremental concentration from baseline-240 minutes (iAUC 0-240 ) compared to controls 0.97 (0.56) vs. 4.78 (0.55); p < 0.001. C max was significantly lower in cases compared to controls [0.38 (0.003) vs. 0.40 (0.003); p < 0.001]. 95% of cases were receiving allopurinol. There was no significant difference between iAUC 0-240 or C max for malabsorbers compared to normal absorbers irrespective of case-control status. The mean (SEM) increase in serum urate between baseline and 30 minutes was 0.04 (0.004)mmol/l in the controls compared to 0.009 (0.002) in the cases (p < 0.001)., Conclusion: The rates of fructose malabsorption are similar in people with and without gout. Allopurinol inhibits the increase in serum urate induced by a fructose load suggesting that people with gout receiving allopurinol may not need to restrict dietary intake of fructose., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives: Gout is one of the most common forms of arthritis. It is well established that urate-lowering therapy that aims for a serum urate less than at least 0.36 mmol/l (6 mg/dl) is required for the successful management of gout. Allopurinol, a xanthine oxidase (XO) inhibitor, is the most commonly used urate-lowering therapy. However, many patients fail to achieve the target serum urate on allopurinol; these patients can be considered to have "inadequate response" to allopurinol. Herein, we examine the potential mechanisms and implications of inadequate response to allopurinol., Methods: The literature was reviewed for potential causes for failure to reach target serum urate in patients receiving allopurinol., Results: The two most common causes of inadequate response to allopurinol are poor adherence and under-dosing of allopurinol. Adherent patients who fail to achieve target serum urate on standard doses of allopurinol form a group that could be considered to be "partially resistant" to allopurinol. There are four potential mechanisms for partial allopurinol resistance: decreased conversion of allopurinol to oxypurinol; increased renal excretion of oxypurinol; abnormality in XO structure and/or function such that oxypurinol is rendered less effective and/or drug interactions., Conclusions: It is important to determine the reasons for failure to achieve treatment targets with allopurinol, particularly as newer agents become available. The knowledge of the mechanisms for inadequate response may help guide the clinician towards making a therapeutic choice that is more likely to result in achieving the serum urate target., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objectives: To determine whether serum urate (SU) fulfills the Outcome measures in Rheumatology (OMERACT) soluble biomarker criteria., Methods: The OMERACT soluble biomarker criteria were adapted for use in chronic gout. Potential outcome measures for use in chronic gout were identified. The literature was reviewed to determine which of the potential outcome measures were appropriate and whether there was evidence within the current literature to fulfill the OMERACT biomarker criteria., Results: The assay for measurement of SU is reliable, internationally standardized, and readily accessible for use in clinical practice. The effects of sources of variability, including age, sex, ethnicity, circadian rhythms, body mass index, renal/hepatic function, and fasting, are well documented. Tophus regression was identified as appropriate structural outcome measure; however, given that not all patients have clinically apparent tophi, the number of gout flares is also identified as a key outcome measure., Conclusions: Serum urate fulfills all the OMERACT biomarker criteria with the exception of its effects on outcome measures. Further analysis of existing and new data sets to determine whether a reduction in SU predicts a reduction in gout flares, the number/size of tophi, and patient reported outcomes using validated measures for these outcomes are required., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objectives: To assess the safety and efficacy of combination therapy in recent-onset rheumatoid arthritis (RA), with dose adjustments determined by response, in a clinic setting over 3 years., Methods: Disease-modifying antirheumatic drug (DMARD)-naive patients with RA of median duration of 12 weeks (n = 61) attending an early arthritis clinic were treated with methotrexate, sulfasalazine, hydroxychloroquine, and fish oil. Dosage adjustments and additions of further DMARDs were contingent on response to therapy and tolerance. Outcome measures for efficacy were Disease Activity Score (DAS28), clinical remission, and modified Sharp radiographic score and for safety, adverse events, and DMARD withdrawal., Results: At baseline, subjects had at least moderately active disease (mean +/- SD DAS28 was 5.3 +/- 1.1), impaired function as measured by the modified Health Assessment Questionnaire (mHAQ) (0.9 +/- 0.5), and 37% had bone erosions. By 3 months, 29% were in remission; this increased to 54% at 3 years. The greatest fall in DAS28 and improvement in mHAQ scores occurred in the first 12 months. Erosions were detected in 62% at 3 years. The mean dose of parenteral glucocorticoid was equivalent to 0.1 mg/d of prednisolone. After 3 years, 48% remained on triple therapy; fish oil was consumed by 75% of patients, and 21% used nonsteroidal anti-inflammatory drugs. Gastrointestinal intolerance was the most frequent unwanted event (leading to DMARD withdrawal in 17 patients). Sulfasalazine was most frequently withdrawn (30%)., Conclusion: This implementation study demonstrates the feasibility, safety, and efficacy of combination therapy with inexpensive DMARDs, fish oil, and minimal glucocorticoid use, in routine clinical practice using predefined rules for dosage adjustment.

Introduction: Rheumatoid arthritis is a common inflammatory condition. A large number of patients seek alternative or complementary therapies of which diet is an important component. This article reviews the evidence for diet in rheumatoid arthritis along with the associated concept of oral tolerization., Methods: References were taken from Medline from 1966 to September 2004. The keywords, rheumatoid arthritis, diet, n-3 fatty acids, vitamins, and oral tolerization, were used., Results: Randomized controlled trials (RCTs) indicate that dietary supplementation with n-3 fatty acids provides modest symptomatic benefit in groups of patients with rheumatoid arthritis. Epidemiological studies and RCTs show cardiovascular benefits in the broader population and patients with ischemic heart disease. A number of mechanisms through which n-3 fats may reduce inflammation have been identified. In a small number of patients with rheumatoid arthritis, other dietary manipulation such as fasting, vegan, and elimination diets may have some benefit. However, many of these diets are impractical or difficult to sustain long term., Conclusions: Dietary manipulation provides a means by which patients can a regain a sense of control over their disease. Dietary n-3 supplementation is practical and can be easily achieved with encapsulated or, less expensively, bottled fish oil.