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Objectives: Patients with rheumatoid arthritis (RA) have reduced serum low-density lipoprotein cholesterol (LDL-c), which increases following therapeutic IL-6 blockade. We aimed to define the metabolic pathways underlying these lipid changes., Methods: In the KALIBRA study, lipoprotein kinetic studies were performed on 11 patients with severe active RA at baseline and following three intravenous infusions of the IL-6R blocker tocilizumab. The primary outcome measure was the fractional catabolic rate (FCR) of LDL., Results: Serum total cholesterol (4.8 vs 5.7 mmol/L, p=0.003), LDL-c (2.9 vs 3.4 mmol/L, p=0.014) and high-density lipoprotein cholesterol (1.23 vs 1.52 mmol/L, p=0.006) increased following tocilizumab therapy. The LDL FCR fell from a state of hypercatabolism to a value approximating that of the normal population (0.53 vs 0.27 pools/day, p=0.006). Changes in FCR correlated tightly with changes in serum LDL-c and C-reactive protein but not Clinical Disease Activity Index., Conclusions: Patients with RA have low serum LDL-c due to hypercatabolism of LDL particles. IL-6 blockade normalises this catabolism in a manner associating with the acute phase response (and thus hepatic IL-6 signalling) but not with RA disease activity as measured clinically. We demonstrate that IL-6 is one of the key drivers of inflammation-driven dyslipidaemia., Competing Interests: Competing interests: IM, NS, DM, CP and DP have received honoraria from or provided consultancy services for Roche / Chugai. JR has received personal fees from Janssen outside the submitted work. MC reports no relevant conflicts of interest., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Psoriatic arthritis is a common inflammatory arthropathy that occurs in approximately 25% of psoriasis patients. Due to significant advances in therapeutics--mainly the advent of biologic therapy--the disease has been subject to intense investigation recently. This review summarizes recent investigations of disease pathogenesis and clinical treatment. Clinical responses to tumor necrosis factor-blocking agents appear robust and superior to traditional disease-modifying drug responses, whereas other interventions, such as costimulation blockade, require more investigation. The pathogenesis of the disease appears related to T helper 17-polarized immune responses that target skin, joints, and the enthesial compartment. Finally, new insights into the disorder's genetic antecedents are emerging as more cohorts of patients undergo advanced genetic screening methods.

Objective: Evaluation of a complex and variable disease such as rheumatoid arthritis (RA) poses a challenge particularly over the medium to long term. A practical framework to evaluate clinically relevant outcomes over the long term is the "5D" approach of Fries, described in 1980. We describe the 20 year outcome in 52 survivors of a 123 patient cohort in terms of change in discomfort, disability, drug side effects, dollar costs, and deaths., Methods: We studied 123 patients with RA allocated to their first disease modifying antirheumatic drug (DMARD) between 1977 and 1979. All were under the overall care of one physician over the 20 years and were maintained where possible taking a single DMARD. Baseline demographic variables, the Ritchie Articular Index (RAI), Lee functional index, and erythrocyte sedimentation rate (ESR) were initially recorded. The extent to which the demographic and disease variables contributed to need for joint replacement surgery was assessed. Therapies for comorbidity were also documented., Results: At cohort inception mean age was 50 years, RAI was 35, and median disease duration 5.5 years. F:M ratio was 90:33; 96% of patients were positive for rheumatoid factor (RF). Initial median ESR was 55 mm/h. At 20 years, 9 patients (7% of original cohort, 14% of survivors) were lost to followup and 62 (50%) had died. In the 52 survivors RAI, a surrogate for disability, showed a significant improvement (p < 0.0001), but disability measured by Lee functional index showed a deterioration (p = 0.018); 50% underwent joint replacement surgery. Initial ESR and mean ESR over the first 10 years of followup were significantly higher in those who required surgery. Nonsteroidal antiinflammatory drug (NSAID) use declined, but at least 2 deaths and 4 renal deaths that may have been related to therapy were attributed to NSAID use. No unexpected DMARD toxicity or mortality occurred. Concomitant therapy for comorbidity, in particular for cardiovascular disease, osteoporosis, and gastrointestinal disease, increased: more than 60% were on these therapies at 20 year followup., Conclusion: Strategies to improve the outcome of RA in all dimensions should include: earlier referral for expert assessment; avoidance of NSAID gastrointestinal and nephrotoxicity; a more intensive effort to identify effective management of comorbidity and those likely to have a poor outcome. Such patients require sustained, intensive therapy to minimize later disability.