Relationship Between Adalimumab Concentrations, Antidrug Antibodies, and Disease Activity in Rheumatoid Arthritis: A Cross-Sectional Observational Study.

OBJECTIVES: To determine the influence of patient characteristics and disease activity on adalimumab (ADA) concentrations; to assess the relationships between ADA concentrations, the presence of antidrug antibodies (ADAb), and disease activity in rheumatoid arthritis (RA); and to determine the association between cytokine concentrations and ADA concentrations. METHODS: A cross-sectional study of people with RA receiving ADA for at least 4 weeks was undertaken. Disease activity was assessed by the Disease Activity Score in 28 joints (DAS28), with responders defined as DAS28 ≤ 3.2. Serum and plasma were obtained for ADA concentrations and ADAb, and a panel of cytokines were obtained for a subgroup. ADA concentrations were compared between demographic and clinical subgroups using ANOVA. The independent associations between clinical and demographic features were analyzed using a general linear model. Variables significantly associated with ADA concentrations from the univariate analyses were entered into multivariate analyses. RESULTS: Of the 156 participants, 69.2% were female and the mean age was 57.4 (SD 12.7) years. Multivariate analysis revealed that higher C-reactive protein (P < 0.001) and higher weight (P < 0.004) were independently associated with lower ADA concentrations. ADA concentrations were higher in those with DAS28 ≤ 3.2 compared to those with DAS28 > 3.2 (median 10.8 [IQR 6.4-20.8] mg/L vs 7.1 [IQR 1.5-12.6] mg/L, P < 0.001). There was a significant negative correlation between interleukin 6 (IL-6) and ADA concentrations (r = -0.04, P < 0.01). CONCLUSION: ADA concentration correlates negatively with markers of inflammatory disease activity in RA, including IL-6. ADA concentration in the range 5 to 7 mg/L over the dose interval are associated with better disease control.

Plasma interleukin-23 and circulating IL-17A+IFNγ+ ex-Th17 cells predict opposing outcomes of anti-TNF therapy in rheumatoid arthritis.

OBJECTIVES: TNF-α inhibitors are widely used in rheumatoid arthritis (RA) with varying success. Response to TNF-α inhibition may reflect the evolution of rheumatoid inflammation through fluctuating stages of TNF-α dependence. Our aim was to assess plasma concentrations of Th-17-related cytokines and the presence of circulating effector T-cells to identify predictors of response to TNF-α inhibitors. METHODS: Ninety-three people with RA were seen prior to and 4-6 months after commencing etanercept or adalimumab. Plasma concentrations of Th17-related cytokines, circulating effector T-cells, their production of relevant transcription factors and intracellular cytokines were measured at baseline. EULAR response criteria were used to define poor (ΔDAS28 ≤ 1.2 and/or DAS28 > 3.2) and good (ΔDAS28 > 1.2 and DAS28 ≤ 3.2) responders. Multivariate logistic regression was used to identify predictors of response. RESULTS: Participants with plasma IL-23 present at baseline were more likely to be poor responders [15/20 (75%) of IL-23+ versus 36/73 (49.3%) of IL-23-; p = 0.041]. While frequencies of Th1, Th17, ex-Th17 and Treg cell populations were similar between good and poor responders to anti-TNF therapy, IL-17A+IFNγ+ ex-Th17 cells were more prevalent in good responders (0.83% of ex-TH17 cells) compared to poor responders (0.24% of ex-Th17 cells), p = 0.023. Both plasma IL-23 cytokine status (OR = 0.17 (95% CI 0.04-0.73)) and IL-17A+IFNγ+ ex-Th17 cell frequency (OR = 1.64 (95% CI 1.06 to 2.54)) were independently associated with a good response to anti-TNF therapy. Receiver operator characteristic (ROC) analysis, including both parameters, demonstrated an area under the ROC curve (AUC) of 0.70 (95% CI 0.60-0.82; p = 0.001). CONCLUSIONS: Plasma IL-23 and circulating IL-17A+IFNγ+ ex-Th17 cells are independently associated with response to anti-TNF therapy. In combination, plasma IL-23 and circulating IL-17A+IFNγ+ ex-Th17 cells provide additive value to the prediction of response to anti-TNF therapy in RA.

An association of smoking with serum urate and gout: A health paradox.

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.

Improving gout education from patients' perspectives: a focus group study of Maori and Pakeha people with gout.

INTRODUCTION Gout is a common form of arthritis that is typically managed in primary care. Gout management guidelines emphasise patient education for successful treatment outcomes, but there is limited literature about the educational experiences of people living with gout in New Zealand, particularly for Maori, who have higher gout prevalence and worse gout outcomes than Pakeha. AIM To explore gout patient education in primary care from the perspectives of Maori and Pakeha people with gout. METHODS In total, 69 people with gout were recruited through primary care providers in three locations across New Zealand. Nine semi-structured focus groups were run with Maori and Pakeha participants in separate groups. RESULTS Thematic analysis yielded two themes in relation to gout education: (i) 'Multiple sources of gout education'; and (ii) 'Gaps in gout knowledge'. Participants received education from general practitioners, educational resources, family and friends, and their own experiences. Maori participants preferred information to be kanohi-ki-te-kanohi (face-to-face) and with significant others present where necessary. Participants disclosed gaps in gout's epidemiology and management. Pakeha and Maori participants reported limited understanding of the genetic basis of gout or the biological underpinnings of the condition and its treatments, but learned treatment adherence through experience. DISCUSSION Despite improved gout patient education, knowledge gaps remain and may contribute to poor medication adherence. Gout patient education interventions need to be tailored to culture and incorporate suitable methods of disseminating information about gout management.

Education Preferences of People With Gout: Exploring Differences Between Indigenous and Nonindigenous Peoples from Rural and Urban Locations.

OBJECTIVE: Gout typically responds well to medications, but adherence might be improved by education that meets individuals' needs in a way that is inclusive of their ethnicity and rurality. The aim of this study was to compare education preferences of Maori and New Zealand European (NZEuropean) individuals with gout, and of those living in rural or urban areas. METHODS: People with gout managed in primary care were recruited from 2 rural regions and 1 city within Aotearoa/New Zealand. Focus groups were held with 26 Maori and 42 NZEuropean participants (44 rural, 24 urban). Participants discussed education preferences for diet, medication, and ways of communicating. The nominal group technique was employed, whereby the group compiled a list of ideas and then participants individually ranked the 3 most important ideas for each topic. RESULTS: The most frequently prioritized ideas for the 3 topics were knowing one's own food triggers, knowing side effects of medications, and communicating via a general practitioner (GP) or specialist. More Maori participants prioritized natural remedies, easy to understand information, and communicating via television. More NZEuropean participants prioritized knowing the kinds of alcohol that trigger gout, communicating via GP/specialist, and receiving written information. More urban participants prioritized knowing to stay hydrated and medication doses as important information. CONCLUSION: Maori and NZEuropean individuals with gout report different understandings and education preferences around personal triggers of gout, treatment options, and ways of receiving information about gout. Further research is required to develop ethnicity-specific gout education resources internationally.

Fructose malabsorption in people with and without gout: A case-control study.

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 (iAUC0-240) compared to controls 0.97 (0.56) vs. 4.78 (0.55); p < 0.001. Cmax 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 iAUC0-240 or Cmax 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.