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Objective We aimed to evaluate the associations between response to algorithm‐directed treat‐to‐target conventional synthetic disease‐modifying antirheumatic drug therapy and potentially modifiable lifestyle factors, including dietary fish oil supplementation, body mass index (BMI), and smoking history in a rheumatoid arthritis (RA) inception cohort. Methods Patients with RA with a duration of less than 12 months were reviewed every 3 to 6 weeks to adjust therapy according to disease response. All patients received advice to take fish oil supplements, and omega‐3 status was measured as plasma levels of eicosapentaenoic acid (EPA). Lifestyle factors and other variables potentially prognostic for 28‐joint Disease Activity Score (DAS28) remission and DAS28 low disease activity (LDA) at the 12‐month visit were included in multivariable logistic regression models. Results Of 300 participants, 57.7% reached DAS28 LDA, and 43.7% were in DAS28 remission at 1 year. Increase in plasma EPA was associated with an increase in the odds of being in LDA (adjusted odds ratio [OR] = 1.27; P < 0.0001) and remission (adjusted OR = 1.21; P < 0.001). There was some evidence that the effect of BMI on LDA might be modified by smoking history. An increase in BMI was associated with a decrease in the odds of being in LDA in current and former smokers but had no impact on LDA in patients who had never smoked. There were no meaningful associations between BMI or smoking history and remission. Conclusion Omega‐3 status, BMI, and smoking history are potential predictors of outcome in early RA. The possibility of an effect modification by smoking on the predictive value of BMI merits further investigation.

Leflunomide is a commonly used disease-modifying drug in the treatment of rheumatoid arthritis (RA). Its effects are mediated via inhibition of dihydroorotate dehydrogenase (DHODH) by its active metabolite teriflunomide, and the pharmacokinetics of teriflunomide are highly variable. Our objective was to examine the association between the DHODH haplotype and plasma teriflunomide concentration with response to leflunomide in patients with RA where leflunomide was added to an existing disease-modifying drug regimen after failure to achieve an adequate response with conventional triple therapy.Patients with RA who were taking, or were about to initiate, leflunomide were included. Participant characteristics, including the DHODH haplotype, were determined. Up to 5 plasma samples were collected after leflunomide was initiated for assays of total and free teriflunomide concentration. Disease activity was determined via the 28-joint Disease Activity Score (DAS28). The association between DAS28 scores and patient covariates was determined by linear mixed-effects modeling.A total of 67 patients were included in the study. The DAS28 score after initiation of leflunomide was associated with the baseline DAS28 score (β = 0.70, P0.001) and was higher in those who carried the DHODH haplotype 2 (β = 0.56. P = 0.01) and did not carry the shared epitope (β = 0.56, P = 0.013). As total and free plasma teriflunomide concentration increased, the DAS28 score was significantly lower (P0.001 and P = 0.001, respectively). When considering threshold concentrations, teriflunomide concentrations16 mg/liter were associated with a DAS28 score that was 0.33 lower, and when free teriflunomide concentration was35 µg/liter, the DAS28 score was 0.32 lower.Teriflunomide concentration and carriage of the DHODH haplotype 2 are associated with response to leflunomide in patients with RA, and a total plasma teriflunomide concentration of at least 16 mg/liter is needed to maximize the likelihood of response.

Aim: To Investigate the prevalence of seroconversion to ACPA after commencement of triple disease-modifying anti-rheumatic drug (DMARD) treat-to-target therapy. Background: Anti-citrullinated peptide antibody (ACPA) and rheumatoid factor (RF) define ‘seropositive’ rheumatoid arthritis (RA). Both predict unfavourable disease course, development of extra-articular features and treatment outcomes. We investigated the prevalence of seroconversion to ACPA after commencement of triple disease-modifying anti-rheumatic drug (DMARD) treat-to-target therapy. Methods: DMARD-naïve patients with RA according to the 1987 American College of Rheumatology criteria and disease duration of

Background: Identification of key determinants of medication adherence may assist with designing interventions to improve this important parameter. The aim of the study was to determine the rate and predictors of self-reported medication adherence in patients with rheumatoid arthritis (RA) over one-year follow-up. Methods: Socio-demographic, disease, therapy and patient-related factors were obtained from a longitudinal observational cohort of RA patients between May 2014 and June 2016. Medication adherence was measured using self-reported Compliance Questionnaire for Rheumatology (CQR) at baseline, 6 and 12 months. Mixed-effects modelling was used to investigate the relationship between adherence and potential predictors. Result: Of 185 patients invited, 110 were included in the study. The median level of adherence was 71%-74% during the study period. Around 27%-30% of patients achieved > 80% adherence, while roughly one-fifth reported a CQR score within the lower quartile (CQR

Anaplastic large cell lymphomas (ALCL) comprise a group of rare, related T-cell neoplasms that typically present on the extremities. Infrequently, cutaneous ALCL can involve the breast, where it is near ubiquitously associated with breast implants. Here, we present the rare case of a 70-year-old woman with primary cutaneous ALCL of the breast with no history of breast augmentation. This serves as an important reminder that in some instances, breast ALCL can be idiopathic. Further, given the potential for malignancy, any changes to the breast skin should be diagnosed quickly in order to ensure rapid delivery of the appropriate treatment.

This author accepted manuscript (post print) is made available following a 12 month embargo from the date of publication (26 October 2016) in accordance with the publisher copyright policy.

Psoriatic arthritis (PsA) may develop in up to a third of people with psoriasis and can be erosive in 40-60% of patients early on, resulting in functional impairment and reduced quality of life. In recent years with the introduction of new medications and wider use of musculoskeletal ultrasound (US) imaging in clinical practice, the possibility of earlier US diagnosis in patients with psoriasis in the pre-clinical phase of PsA has been examined. US detection of subclinical synovitis and enthesitis in psoriasis patients without musculoskeletal involvement will be discussed. The clinical spectrum of PsA is broad with five target areas of joints, tendons, entheses, skin and nails. Each domain will be discussed with their relevant US findings, focussing on synovitis, enthesitis and dactylitis. Specifically, features of enthesitis on US can be divided into those of reversible soft tissue inflammation and irreversible tissue damage. There is increasing use of US in evaluating nail involvement in psoriasis as this feature increases the probability of developing PsA. In patients with predominantly hand involvement, US enables differentiation of PsA from other inflammatory arthritides, such as rheumatoid arthritis, using specific extra-synovial US patterns of inflammation. Examples include peritenonitis of the extensor digitorum tendon at the metacarpophalangeal joints. Thickening of the flexor tendon pulleys may be predictive of PsA in the setting of early arthritis. Psoriatic related polyenthesitis without clinically swollen joints or increased inflammatory markers can mimic fibromyalgia with multiple tender points. US detection of enthesitis especially if power Doppler positive may assist by providing an objective assessment of disease activity. More recently, the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) US Working Group has developed a PsA US enthesitis scoring system, addressing the elementary inflammatory and structural components and determining which entheseal sites should be scanned. The utility of US in monitoring disease activity in PsA to support clinical assessment will be discussed, including guidance in tapering therapy in clinical remission. The ongoing prospective US in PsA Treatment Study (UPSTREAM) aims to identify clinical and US predictors of treatment response in PsA. Future research should address issues such as the optimal combination for US screening of joints, tendons and entheses, the predictive value of subclinical US inflammatory lesions for future development of PsA and whether US provides any added prognostic value in PsA in those achieving minimal disease activity on therapy.

Medication adherence is believed to be a major contributor to treatment outcomes yet studies quantifying this relationship as rare in rheumatoid arthritis (RA). To determine the association of adherence to DMARD therapy with treatment outcomes among new and existing DMARD users over 2 years. Relevant clinical parameters were obtained from a longitudinal cohort of RA patients, most of who were treated with combination therapy. Patients were classified as adherent if the proportion of days covered for each DMARD was ≥80%. Outcome measures were the change in the disease activity score in 28 joints (DAS28), simplified disease activity index (SDAI), modified health assessment questionnaires (mHAQ) and proportion of patients who achieved response criteria. An inverse propensity-score weighting method was used to estimate the association of adherence with each outcome. Of 194 patients invited, a total of 111 patients (new = 45 and existing = 66 DMARD users) met study eligibility. DMARD-naive patients demonstrated relatively higher rates of adherence compared to existing users. After controlling for confounding variables, adherence was significantly associated with reduction in DAS28 (β = −1.5, 95% CI of β = − 2.17 to −0.83, p < 0.0001), SDAI (β = −9.44, 95% CI of β = −15.53 to −3.35, p = 0.002) and mHAQ (β = −0.269, 95% CI of β, −0.462 to −0.077, p = 0.017) over 2 years among new patients and adherent patients were more likely to achieve most response criteria compared to non-adherent patients. Such associations were not replicated among existing DMARD users. Adherence to combination DMARD therapy was associated with improvements in disease activity and functional outcomes in the first 2 years of therapy. Refereed/Peer-reviewed

Objective:To determine the minimum cut-points for rate of physician compliance with a treat-to-target (T2T)strategy needed to achieve optimal rates of remission or low disease activity (LDA) Method:In this analysis of longitudinal observational data from patients with early RA, physician compliance with a T2T treatment protocol was determined for each clinic visit over 3 years. Remission and LDA were measured by Disease Activity Score in 28 joints (DAS28), simplified disease activity index (SDAI) and clinical disease activity index (CDAI). The minimum physician compliance rates for predicting these outcomes were calculated using receiver operating characteristic (ROC) curves Result:Overall, 149 patients completed 3078 clinic visits over 3 years of follow-up. Treatment decisions com-plied with the T2T protocol in 2343 of these visits (76.1%). The minimum cut-points for physician compliance rates that predicted remission and LDA according to DAS28 were 81.1% and 70.7%, respectively, and to predict remission and LDA according to SDAI, the respective cut-points were 92.7% and 77.4%. Based on these cut-points, three categories of physician compliance with T2T were proposed: high (to maximize the likelihood of achieving remission,>80% according to DAS28 or>90% according to SDAI/CDAI); medium (the minimal physician compliance to achieve LDA, 70–79% according to DAS28 or 75–89% for SDAI/CDAI); and low(

Objective: To identify the disease activity trajectories during intensive triple disease modifying anti-rheumatic drug (DMARD) therapy over 3 years in rheumatoid arthritis (RA) patients and to evaluate the association with treatment persistence. Methods: Disease Activity Score in 28 joints, baseline risk factors and medication usage were obtained from a longitudinal observational cohort of early RA patients, most of whom were treated with combination DMARD therapy consisting of methotrexate, sulfasalazine and hydroxychloroquine. Persistence of each DMARD was defined as the duration of time from initiation to cessation. A group-based trajectory modelling technique was used to identify disease activity trajectories. Result: Three disease activity trajectories (good [43.8%], moderate [39.7%] and poor [16.5%]) were identified in a cohort of 297 patients. Most baseline risk factors, medication usage, the rate of treatment persistence and the effect of persistence on disease activity differed among patients in each of the three trajectories. Although the rate of persistence was higher in the trajectory with a good outcome, the association with persistence was more pronounced among patients who were in the poor outcome trajectory. Persistence with at least two or all three baseline DMARDs was associated with a decrease in disease activity to a broadly similar degree in all trajectories. Conclusion: After correction for other baseline prognostic factors, persistence with initial DMARDs contributes to heterogeneity in disease activity trajectory and there was an association between persistence with initial DMARD therapy and lower long-term disease activity. Refereed/Peer-reviewed

Summary Objectives The purpose of this study was to pilot a brief (6-week) group curriculum for providing mindfulness training to obese individuals, called Mindful Eating and Living (MEAL). Setting and design Participants were recruited through a local Young Men's Christian Association (YMCA) in spring 2006. Data was collected at three time points: baseline, completion of intervention (6 weeks), and 3-month follow-up (12 weeks). Intervention Six weekly two-hour group classes (with two monthly follow-up classes). Content included training in mindfulness meditation, mindful eating, and group discussion, with emphasis on awareness of body sensations, emotions, and triggers to overeat. Main outcome measures Key variables assessed included changes in weight, body-mass index (BMI), eating behavior, and psychological distress. In addition, physiological markers of cardiovascular risk were evaluated including C-reactive protein (hsCRP), adiponectin, low-density lipoprotein (LDL), and plasminogen activator inhibitor-1 (PAI-1). Results Ten obese patients enrolled with a mean BMI of 36.9kg/m 2 [SD±6.2]. The mean weight was 101kg/m 2 and the mean age was 44 years (SD=8.7; range=31–62). Compared to baseline data, participants showed statistically significant increases in measures of mindfulness and cognitive restraint around eating, and statistically significant decreases in weight, eating disinhibition, binge eating, depression, perceived stress, physical symptoms, negative affect, and C-reactive protein. Conclusions This study provides preliminary evidence that a eating focused mindfulness-based intervention can result in significant changes in weight, eating behavior, and psychological distress in obese individuals.

Introduction: Treat-to-target (T2T) strategies using a protocol of pre-defined adjustments of disease-modifying anti-rheumatic drugs (DMARDs) according to disease activity improve outcomes for patients with rheumatoid arthritis (RA). However, successful implementation may be limited by deviations from the protocol. The aim of this study was to determine the prevalence of protocol deviation, explore the reasons and identify subsets of patients in whom treatment protocols are more difficult to follow. Methods: In this retrospective cohort study, treatment-naïve patients with RA of less than one years duration, attending a dedicated early arthritis clinic between 2001 and 2013, were followed for three years from initiation of combination therapy with conventional DMARDs which was subsequently modified according to a T2T protocol. At each clinic visit, whether deviation from the protocol occurred, the type of deviation and the reasons for deviation were assessed. The relationship between protocol deviations and baseline variables was determined using linear regression analysis. Results: In total, 198 patients contributed 3,654 clinic visits. The prevalence of protocol deviations was 24.5% and deviation in at least at one clinic visit was experienced by 90.4% of patients. The median time to first deviation was 30 weeks. Continuing existing treatment rather than intensifying therapy was the most common type of deviation (59.9%). Patient and physician related factors were the most common reasons for deviation, each accounting for 24.7% of deviations, followed by toxicities (23.3%) and comorbidities (20.0%). The prevalence of protocol deviations was lower among patients who achieved remission after three years (13.1%; 162 deviations out of 1,228 visits) compared with those who were not in remission (30.9%; 523/1692) (P

Introduction: Low copy number (CN) of the Fc gamma receptor 3B (FCGR3B) gene has been associated with systemic autoimmune disease. This receptor for IgG is present almost exclusively on neutrophils and plays a role in their interaction with immune complexes. At present the relationship between FCGR3B and rheumatoid arthritis (RA) is unclear. The aim of the present study was to investigate whether low CN of the FCGR3B gene is associated with susceptibility to RA. Method: The FCGR3B CN was determined using a custom Taqman® CN assay (Hs04211858; Applied Biosystems, Foster City, CA, USA) in 197 RA patients, recruited from a tertiary setting, and in 162 population matched controls. Odds ratios for low CN (< 2) and high CN (> 2), both relative to the normal diploid 2CN, were estimated by logistic regression. Results: A significant association between RA and low FCGR3B CN was observed, with frequencies of 13.7% in RA patients compared with 6.2% in controls (odds ratio 2.5, 95% confidence interval 1.2 to 5.4, P = 0.017). No association was observed between low CN and the presence of rheumatoid factor, anti-cyclic citrullinated peptide antibodies or radiographic erosions in RA patients. A meta-analysis including six previous studies confirmed an association between RA and low FCGR3B CN (odds ratio 1.47, 95% confidence interval 1.13 to 1.92, P = 0.004). Conclusions: The present study confirms that a low CN of the FCGR3B gene is associated with susceptibility to RA. The association may be stronger in patients recruited from a tertiary setting, which may relate to disease severity and/or complications. The mechanism of susceptibility remains unclear and further study is required.