Weight Loss for Patients With Gout and Concomitant Obesity: A Proof-of-Concept Randomized Trial.

OBJECTIVE: Despite scarce evidence, guidelines recommend weight loss as a management strategy for patients with gout. We investigated the effect of an intensive dietary intervention on body weight and clinical measures of gout severity in individuals with obesity and gout. METHODS: We conducted a 16-week randomized nonmasked parallel-group trial in Denmark, randomly assigning (one-to-one) individuals with obesity and gout to a low-energy diet or a control diet. The primary outcome was change in body weight. Key secondary outcomes were changes in serum urate (SU) level and visual analog scale-assessed pain and fatigue. RESULTS: Between December 1, 2018, and June 1, 2019, 61 participants were included in the intention-to-treat population and randomly assigned to the intensive diet group (n = 29) or control diet group (n = 32). Participants had a mean age of 60.3 (SD 9.9) years and mean body mass index of 35.6 (SD 5.0), and 59 (97%) were men. After 16 weeks, there was a significant difference in change in body weight between the diet and control groups (-15.4 vs -7.7 kg; difference -7.7 kg [95% confidence interval -10.7 to -4.7], P < 0.001). Despite results being potentially in favor of a low-energy diet, we could not confirm differences in SU level changes and fatigue between groups. No differences in pain and gout flares were observed between groups. No serious adverse events or deaths occurred during the trial. CONCLUSION: An intensive dietary intervention was safe and effectively lowered body weight in people with obesity and gout, but the weight loss did not directly translate into effects on SU level, fatigue, and pain.

Increased cancer risk in patients with cutaneous lupus erythematosus and systemic lupus erythematosus compared with the general population: A Danish nationwide cohort study.

OBJECTIVES: To investigate if patients with cutaneous lupus erythematosus (CLE) or systemic lupus erythematosus (SLE) have an increased risk of cancer compared with the general population, and furthermore to identify specific cancer types associated with increased risk. METHODS: This is an observational cohort study of 5310 patients with CLE or SLE identified in the Danish National Patient Register from 1 January 1995 to 31 December 2014. The cohort was followed up for cancer by linkage to the Danish Cancer Registry. Based on the age, sex, and calendar specific cancer rates of the general population of Denmark, standardised incidence ratios (SIRs) were calculated. RESULTS: The patients with CLE or SLE were followed for 40.724 person-years, each group's average duration of follow-up being 6.9 and 8.1 years. The SIR for overall cancer (except non-melanoma skin cancer (NMSC)) was increased in patients with CLE 1.35 (95%CI 1.15 to 1.58) and patients with SLE 1.45 (95%CI 1.30 to 1.62). Both groups had high risks of hematological - including a 3-4-fold increased risk of non-Hodgkin lymphoma -, pancreatic, and lung cancers. Several cancers associated with oncogenic viruses as liver and tongue/mouth/pharynx were increased in the SLE group, while the risk of ovarian cancer was increased 2-4-fold only in the CLE group. CONCLUSION: The overall risk of cancer was significantly increased in both patients with CLE and SLE. SIRs for hematological, pancreatic and lung cancers were elevated in both groups. Extra awareness of cancer in patients with SLE and patients with CLE should be considered.

Risk of solid cancers overall and by subtypes in patients with psoriatic arthritis treated with TNF inhibitors - a Nordic cohort study.

OBJECTIVES: To investigate whether TNF inhibitors (TNFi) are associated with increased risk of solid cancer in patients with psoriatic arthritis (PsA). METHODS: From the Nordic clinical rheumatology registers (CRR) here: SRQ/ARTIS (Sweden), DANBIO (Denmark), NOR-DMARD (Norway), ROB-FIN (Finland) and ICEBIO (Iceland) we identified PsA patients who started a first TNFi 2001-2017 (n = 9655). We identified patients with PsA not treated with biologics from (i) the CRR (n = 14 809) and (ii) the national patient registers (PR, n = 31 350). By linkage to the national cancer registers, we collected information on incident solid cancer overall and for eight cancer types. We used Cox regression to estimate hazard ratio (HR) with 95% CI of cancer (per country and pooled) in TNFi-exposed vs biologics-naïve, adjusting for age, sex, calendar period, comorbidities and disease activity. We also assessed standardized incidence ratios (SIR) in TNFi-exposed PsA vs the general population (GP). RESULTS: We identified 296 solid cancers among the TNFi-exposed PsA patients (55 850 person-years); the pooled adjusted HR for solid cancer overall was 1.0 (0.9-1.2) for TNFi-exposed vs biologics-naïve PsA from the CRR, and 0.8 (0.7-1.0) vs biologics-naïve PsA from the PRs. There were no significantly increased risks for any of the cancer types under study. The pooled SIR of solid cancer overall in TNFi treated PsA vs GP was 1.0 (0.9-1.1). CONCLUSION: In this large cohort study from five Nordic countries, we found no increased risk of solid cancer in TNFi-treated PsA patients, neither for solid cancer overall nor for eight common cancer types.

Reduction in Upper Limb Joint Surgery Among Rheumatoid Arthritis Patients: An Interrupted Time-Series Analysis Using Danish Health Care Registers.

OBJECTIVE: Joint replacement surgery is a proxy of severe joint damage in rheumatoid arthritis (RA). The aim of this study was to assess the impact of the introduction of biologic disease-modifying antirheumatic drugs (bDMARDs) on the incidence rate (IR) of upper limb joint replacements among newly diagnosed RA patients. METHODS: Using the Danish National Patient Register, patients with incident RA from 1996-2012 were identified. Each patient was matched on age, sex, and municipality, with up to 10 general population controls. The age- and sex-standardized 5-year IR per 1,000 person-years of a composite outcome of any first joint replacement of the finger, wrist, elbow, or shoulder was calculated, and an interrupted time-series analysis was undertaken to investigate trends and changes of the IR in the pre-bDMARD (1996-2001) and the bDMARD eras (2003-2012), with a 1-year lag period in 2002. RESULTS: In total, 18,654 incident patients with RA were identified (mean age 57.6 years, 70.5% women). The IR of joint replacements among patients with RA was stable at 2.46 per 1,000 person-years (95% confidence interval [95% CI] 1.96, 2.96) from 1996 to 2001 but started to decrease from 2003 onwards (-0.08 per 1,000 person-years annually [95% CI -0.20, 0.02]). Compared with patients with RA, the IR among controls in 1996 was 1/17 and increased continuously throughout the study period. CONCLUSION: The IR of upper limb joint replacements started to decrease among patients with RA from 2002 onwards, whereas it increased among controls. Our results suggest an association between the introduction of bDMARDs and a lower need of joint replacements among patients with RA.

Secular trends in the incidence and prevalence of gout in Denmark from 1995 to 2015: a nationwide register-based study.

OBJECTIVE: To investigate temporal trends in the incidence and prevalence of gout in the adult Danish population. METHODS: Using the nationwide Danish National Patient Registry, we calculated the number of incident gout patients (per 100 000 person-years) within each 1 year period from 1995 to 2015 and the prevalence of gout in 2000 and 2015. Further, we calculated age- and gender-specific incidence rates of gout from 1995 to 2015. RESULTS: We identified a total of 45 685 incident gout patients (72.9% males) with a mean age of 65 years (s.d. 16) at diagnosis. In both genders, an increase in age-standardized incidence rates was observed from 32.3/100 000 (95% CI 30.7, 33.9) in 1995 to 57.5/100 000 (95% CI 55.6, 59.5) in 2015 (P < 0.001). Similar trends were observed for 8950 cases diagnosed in rheumatology departments. We likewise observed an increase in the prevalence of gout from 0.29% (95% CI 0.29, 0.30) in 2000 to 0.68% (95% CI 0.68, 0.69) in 2015. CONCLUSIONS: The annual incidence rate of gout increased by almost 80% in Denmark between 1995 and 2015. The prevalence increased by nearly 130% between 2000 and 2015. Reasons for this are unknown but may include an increase in risk factors (e.g. obesity, diabetes mellitus), longer life expectancy and increased awareness of the disease among patients and/or health professionals.

Nutritional recommendations for gout: An update from clinical epidemiology.

OBJECTIVE: To present the evidence for nutritional lifestyle changes recommended for gout patients; an explicit focus will be on the evidence for weight loss in overweight gout patients based on a recent systematic review and to describe methodological details for an upcoming weight loss trial. METHODS: We did a pragmatic but systematic search in MEDLINE for current guidelines that had made an attempt to make nutritional recommendations for gout. The quality of the evidence for the nutritional recommendations was evaluated based on the guidelines' own ratings and converted into a common simple version based on the GRADE system. The recently published systematic review on weight loss for gout, was based on six databases from which longitudinal studies that had quantified the effects following weight loss were included. The internal validity was assessed with the ROBINS-I tool and the quality of the evidence was assessed with the GRADE approach. Based on the results of the systematic review, a trial was designed, adhering to the principles of evidence based research. RESULTS: We included 17 guidelines. Most guidelines recommend avoiding or limiting alcohol intake (15; i.e. 88%), lose weight if relevant (12; 71%), and reduce fructose intake (11; 65%). The majority of the evidence for the nutritional recommendations was rated Moderate/Low or Very Low quality. Our recent systematic review on weight loss included 10 studies and found that the available evidence indicates beneficial effects of weight loss for overweight and obese gout patients, but the evidence is of low to moderate quality. As a consequence, researchers from the Parker Institute are launching a randomized trial to explore the short-term effects related to a diet-induced weight loss in obese gout patients. CONCLUSIONS: The nutritional recommendations for gout are generally based on low quality evidence. In terms of weight loss as a management strategy, the available evidence is in favor of weight loss for overweight/obese gout patients. However, since the current evidence consists of only a few studies (mostly observational) of low methodological quality, the Parker Institute are now initiating a rigorous exploratory randomized trial. Similar efforts are needed for other nutritional management strategies for gout.

Gender differences in biologic treatment outcomes-a study of 1750 patients with psoriatic arthritis using Danish Health Care Registers.

Objective: We aimed to investigate gender differences in disease manifestations, patient-reported outcomes, comorbidities and treatment effectiveness among patients with PsA treated with their first TNFα inhibitor (TNFI). Methods: In this observational cohort study, the DANBIO register provided prospectively collected data on PsA patients who initiated their first TNFI in 2000-15. Comorbidity information was achieved from the Danish Nationwide Patient Register. Response to treatment was assessed according to EULAR and ACR criteria at 3 and 6 months. Cox and logistic regression models analysed the impact of gender on TNFI persistence and response, respectively, while adjusting for a priori selected confounders including clinical-, laboratory- and patient-reported factors, comorbidities and lifestyle characteristics. Results: A total of 1750 PsA patients (935 women) were included. At baseline, women were older (49 years/47 years), more often smokers (32%/26%), had worse patient-reported scores (e.g. global score 71 mm/65 mm) and higher frequencies of hospital-diagnosed anxiety or depression (7%/4%) and chronic pulmonary disease (7%/3%) than men (all P < 0.01). Median TNFI persistence was 3.8 years (95% CI: 3.0, 5.7) in men vs 1.4 (1.1, 1.8) in women (P < 0.001). Men had higher odds of achieving response after 3 and 6 months, for example, adjusted odds ratio = 3.2 (1.6, 6.1) for EULAR good/moderate response (vs women) at 6 months. Conclusion: Male gender was strongly associated with greater TNFI treatment effectiveness. Adjustment for baseline risk factors including patient-reported outcomes, disease activity, comorbidities and lifestyle factors did not influence this relationship, which suggests a role of biological factors.

Incidence of hip and knee replacement in patients with rheumatoid arthritis following the introduction of biological DMARDs: an interrupted time-series analysis using nationwide Danish healthcare registers.

OBJECTIVES: To study the impact of the introduction of biological disease-modifying anti-rheumatic drugs (bDMARDs) and associated rheumatoid arthritis (RA) management guidelines on the incidence of total hip (THR) and knee replacements (TKR) in Denmark. METHODS: Nationwide register-based cohort and interrupted time-series analysis. Patients with incident RA between 1996 and 2011 were identified in the Danish National Patient Register. Patients with RA were matched on age, sex and municipality with up to 10 general population comparators (GPCs). Standardised 5-year incidence rates of THR and TKR per 1000 person-years were calculated for patients with RA and GPCs in 6-month periods. Levels and trends in the pre-bDMARD (1996-2001) were compared with the bDMARD era (2003-2016) using segmented linear regression interrupted by a 1-year lag period (2002). RESULTS: We identified 30 404 patients with incident RA and 297 916 GPCs. In 1996, the incidence rate of THR and TKR was 8.72 and 5.87, respectively, among patients with RA, and 2.89 and 0.42 in GPCs. From 1996 to 2016, the incidence rate of THR decreased among patients with RA, but increased among GPCs. Among patients with RA, the incidence rate of TKR increased from 1996 to 2001, but started to decrease from 2003 and throughout the bDMARD era. The incidence of TKR increased among GPCs from 1996 to 2016. CONCLUSION: We report that the incidence rate of THR and TKR was 3-fold and 14-fold higher, respectively among patients with RA compared with GPCs in 1996. In patients with RA, introduction of bDMARDs was associated with a decreasing incidence rate of TKR, whereas the incidence of THR had started to decrease before bDMARD introduction.

Predictors of revision, prosthetic joint infection and mortality following total hip or total knee arthroplasty in patients with rheumatoid arthritis: a nationwide cohort study using Danish healthcare registers.

OBJECTIVES: To investigate predictors of 10-year risk of revision and 1-year risk of prosthetic joint infection (PJI) and death following total hip/total knee arthroplasty (THA/TKA) in (1) patients with rheumatoid arthritis (RA) compared with patients with osteoarthritis (OA); and (2) patients with RA treated with biological disease-modifying antirheumatic drugs (bDMARD) within 90 days preceding surgery compared with non-treated. METHODS: Register-based cohort study using the Danish National Patient Register, the DANBIO rheumatology register (RA-specific confounders and treatment episodes) and the Danish Hip and Knee Arthroplasty Registers. Survival analyses were used to calculate confounder-adjusted sub-HRs (SHR) and HRs. RESULTS: In total, 3913 patients with RA with THA/TKA were compared with 120 499 patients with OA. Patients with RA had decreased risk of revision (SHR 0.71 (0.57-0.89)), but increased risk of PJI (SHR=1.46 (1.13-1.88)) and death (HR=1.25 (1.01-1.55)). In DANBIO, 345 of 1946 patients with RA with THA/TKA had received bDMARD treatment within 90 days preceding surgery. bDMARD-treated patients did not have a statistically significant increased risk of revision (SHR=1.49 (0.65-3.40)), PJI (SHR=1.61 (0.70-3.69)) nor death (HR=0.75 (0.24-2.33)) compared with non-treated. Glucocorticoid exposure (HR=2.87 (1.12-7.34)) and increasing DAS28 (HR=1.49 (1.01-2.20)) were risk factors for mortality. CONCLUSION: Patients with RA had a decreased 10-year risk of revision while the risk of death and PJI was increased compared with patients with OA following THA/TKA. bDMARD exposure was not associated with statistically significant increased risk of neither PJI nor death in this study. Glucocorticoid exposure and increased disease activity were associated with an increased risk of death.