Common Rheumatic Disease Research Articles

Knee Acoustic Emissions as a Digital Biomarker of Disease Status in Juvenile Idiopathic Arthritis.

In this paper, we quantify the joint acoustic emissions (JAEs) from the knees of children with juvenile idiopathic arthritis (JIA) and support their use as a novel biomarker of the disease. JIA is the most common rheumatic disease of childhood; it has a highly variable presentation, and few reliable biomarkers which makes diagnosis and personalization of care difficult. The knee is the most commonly affected joint with hallmark synovitis and inflammation that can extend to damage the underlying cartilage and bone. During movement of the knee, internal friction creates JAEs that can be non-invasively measured. We hypothesize that these JAEs contain clinically relevant information that could be used for the diagnosis and personalization of treatment of JIA. In this study, we record and compare the JAEs from 25 patients with JIA−10 of whom were recorded a second time 3–6 months later—and 18 healthy age- and sex-matched controls. We compute signal features from each of those record cycles of flexion/extension and train a logistic regression classification model. The model classified each cycle as having JIA or being healthy with 84.4% accuracy using leave-one-subject-out cross validation (LOSO-CV). When assessing the full JAE recording of a subject (which contained at least 8 cycles of flexion/extension), a majority vote of the cycle labels accurately classified the subjects as having JIA or being healthy 100% of the time. Using the output probabilities of a JIA class as a basis for a joint health score and test it on the follow-up patient recordings. In all 10 of our 6-week follow-up recordings, the score accurately tracked with successful treatment of the condition. Our proposed JAE-based classification model of JIA presents a compelling case for incorporating this novel joint health assessment technique into the clinical work-up and monitoring of JIA.

Concerns, Healthcare Use, and Treatment Interruptions in Patients With Common Autoimmune Rheumatic Diseases During the COVID-19 Pandemic.

To assess concerns and healthcare-related behaviors of patients with autoimmune rheumatic diseases during the coronavirus disease 2019 (COVID-19) pandemic. Adults from the United States with rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), and systemic lupus erythematosus (SLE) from the ArthritisPower Patient-Powered Research Network and CreakyJoints patient community completed surveys. Concerns and behaviors were compared among patients with different autoimmune conditions, disease-modifying antirheumatic drug (DMARD) use, and geographic measures of urban status, income, education, and COVID-19 activity. Among 1517 participants (925 RA, 299 PsA, 185 AS, 108 SLE), mean age was 55.1 years, 88.3% were female, and 89.5% were White. COVID-19 concerns were similar across the country and were higher in biologic users (P < 0.001). Avoidance of doctor's office visits (56.6%) or laboratory testing (42.3%) and use of telehealth (29.5%) were more common in urban areas. Among participants receiving a DMARD without COVID-19 or other respiratory illness, 14.9% stopped a DMARD, with 78.7% of DMARD interruptions not recommended by a physician. DMARD stopping was more common in participants with lower socioeconomic status (SES) and in participants who avoided an office visit (OR 1.46, 95% CI 1.04-2.04) or reported lack of telehealth availability OR 2.26 (95% CI 1.25-4.08). In the early months of the COVID-19 pandemic, patients with RA, PsA, AS, and SLE frequently avoided office visits and laboratory testing. DMARD interruptions commonly occurred without the advice of a physician and were associated with SES, office visits, and telehealth availability, highlighting the need for adequate healthcare access and attention to vulnerable populations during the pandemic.

Mini-Review: Human Microbiome and Rheumatic Diseases.

Rheumatoid arthritis and spondyloarthropathy are the most common inflammatory rheumatic diseases. As the human microbiome is involved in the immune homeostasis, it has the potential to be a key factor in the development of autoimmune diseases and rheumatic diseases. In this article, we review the role of various human microbiota on the pathogenesis of rheumatic diseases, focusing on spondylarthritis and rheumatoid arthritis.

Fused Omics Data Models Reveal Gut Microbiome Signatures Specific of Inactive Stage of Juvenile Idiopathic Arthritis in Pediatric Patients.

Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children. Herein, we evaluated the relationship between the gut microbiome (GM) and disease phenotype by an integrated omics fused approach. In a multicenter, observational cohort study, stools from Italian JIA patients were collected at baseline, active, and inactive disease stages, and their GM compared to healthy controls (CTRLs). The microbiota metabolome was analyzed to detect volatile- and non-volatile organic compounds (VOCs); the data were fused with operational taxonomic units (OTUs) from 16S RNA targeted-metagenomics and classified by chemometric models. Non-VOCs did not characterize JIA patients nor JIA activity stages compared to CTRLs. The core of VOCs, (Ethanol, Methyl-isobutyl-ketone, 2,6-Dimethyl-4-heptanone and Phenol) characterized patients at baseline and inactive disease stages, while the OTUs represented by Ruminococcaceae, Lachnospiraceae and Clostridiacea discriminated between JIA inactive stage and CTRLs. No differences were highlighted amongst JIA activity stages. Finally, the fused data discriminated inactive and baseline stages versus CTRLs, based on the contribution of the invariant core of VOCs while Ruminococcaceae concurred for the inactive stage versus CTRLs comparison. In conclusion, the GM signatures enabled to distinguish the inactive disease stage from CTRLs.

Time Trends in Opioid Use Disorder Hospitalizations in Gout, Rheumatoid Arthritis, Fibromyalgia, Osteoarthritis, and Low Back Pain.

To examine opioid use disorder (OUD)-related hospitalizations and associated healthcare utilization outcomes in people with 5 common musculoskeletal diseases (MSD). We used the US National Inpatient Sample (NIS) data from 1998 to 2014 to examine the rates of OUD hospitalizations (per 100,000 NIS claims overall), time trends, and outcomes in 5 common rheumatic diseases: gout, rheumatoid arthritis (RA), fibromyalgia (FM), osteoarthritis (OA), and low back pain (LBP). OUD hospitalization rate per 100,000 total NIS claims in 1998-2000 vs 2015-2016 (and increase) were as follows: gout, 0.05 vs 1.88 (36-fold); OA, 0.68 vs 10.22 (14-fold); FM, 0.53 vs 6.98 (12-fold); RA, 0.30 vs 3.16 (9.5-fold); and LBP, 1.17 vs 7.64 (5.5-fold). The median hospital charges and hospital stays for OUD hospitalizations were as follows: gout, $18,363 and 2.5 days; RA, $17,398 and 2.4 days; FM, $15,772 and 2.1 days; OA, $16,795 and 2.4 days; and LBP, $13,722 and 2.0 days. In-hospital mortality rates ranged from 0.9% for LBP and FM to 1.7% for gout with OUD hospitalizations. Compared to those without each MSD, age-, sex-, race-, and income-adjusted total hospital charges (inflation-adjusted) for OUD hospitalizations with each rheumatic disease were as follows: gout, $697 higher; OA, $4759 lower; FM, $2082 lower; RA, $1258 lower; and LBP, $4944 lower. OUD hospitalizations increased in all 5 MSD studied, but the rate of increase differed. Awareness of these OUD hospitalization trends in 5 MSD among providers, policy makers, and patients is important. Development and implementation of interventions, policies, and practices to potentially reduce OUD-associated effects in people with rheumatic diseases is needed.

Value of Screening for Osteoporosis among Children with Juvenile Idiopathic Arthritis

Juvenile idiopathic arthritis (JIA) is one of the most common rheumatic diseases in children. In all subtypes of JIA, a low bone mass has been detected in a high percentage of children due to failure to develop adequate bone mineralization.

Recommendations for the Management of Uveitis Associated With Juvenile Idiopathic Arthritis: The Czech and Slovak adaptation of SHARE Initiative.

Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children and uveitis is its most important extra-articular manifestation. Evidence-based recommendations are available only to alimited extent and therefore JIA associated uveitis management is mostly based on physicians experience. Consequently, treatment practices differ widely, both nationally and internationally. Therefore, an effort to optimize and publish recommendations for the care of children and young adults with rheumatic diseases was launched in 2012 as part of the international project SHARE (Single Hub and Access Point for Pediatric Rheumatology in Europe) to facilitate clinical practice for paediatricians and (paediatric) rheumatologists. The aim of this work was to translate published international SHARE recommendations for the diagnosis and treatment of JIA associated uveitis and to adapt them for use in the Czech and Slovak Republics. International recommendations were developed according to the standard methodology of the European League against Rheumatism (EULAR) by agroup of nine experienced paediatric rheumatologists and three experts in ophthalmology. It was based on asystematic literature review and evaluated in the form of an online survey and subsequently discussed using anominal group technique. Recommendations were accepted if &gt; 80% agreement was reached (including all three ophthalmologists). Atotal of 22 SHARE recommendations were accepted: 3 on diagnosis, 5 on disease activity assessment, 12 on treatment and 2 on future recommendations. Translation of the original text was updated and modified with data specific to the czech and slovak health care systems and supplemented with aproposal for aprotocol of ophthalmological dispensarization of paediatric JIA patients and atreatment algorithm for JIA associated uveitis. Conclusion: The aim of the SHARE initiative is to improve and standardize care for paediatric patients with rheumatic diseases across Europe. Therefore, recommendations for the diagnosis and treatment of JIA-associated uveitis have been formulated based on the evidence and agreement of leading European experts in this field.

IMPORTANCE OF TEMPOROMANDIBULAR JOINT EVALUATION IN JUVENILE IDIOPATHIC ARTHRITIS: A CASE REPORT

Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in childhood and often involves the temporomandibular joint (TMJ). Herein we present a case of a 9-year-old female patient who sought a rheumatologist with a main complaint of hip pain and was diagnosed with JIA. On that occasion, the TMJ was not evaluated. The disease was controlled with nonsteroidal anti-inflammatory drugs and methotrexate, and the patient was monitored through laboratory tests. Three years after the initial diagnosis, during a dental appointment, facial asymmetry was observed, without painful symptomatology. The clinical examination revealed mandibular retrognathism and malocclusion, with midline deviation to the right. Image studies showed erosion and important flattening of the right condyle. The orthodontic treatment allowed correction of malocclusion, but facial asymmetry persisted. TMJ should always be evaluated in patients with JIA, regardless of the presence of signs or symptoms, because their involvement is frequent and may occur silently.

Novel Muscle Imaging in Inflammatory Rheumatic Diseases-A Focus on Ultrasound Shear Wave Elastography and Quantitative MRI.

In recent years, imaging has played an increasing role in the clinical management of patients with rheumatic diseases with respect to aiding diagnosis, guiding therapy and monitoring disease progression. These roles have been underpinned by research which has enhanced our understanding of disease pathogenesis and pathophysiology of rheumatology conditions, in addition to their key role in outcome measurement in clinical trials. However, compared to joints, imaging research of muscles is less established, despite the fact that muscle symptoms are very common and debilitating in many rheumatic diseases. Recently, it has been shown that even though patients with rheumatoid arthritis may achieve clinical remission, defined by asymptomatic joints, many remain affected by lingering constitutional systemic symptoms like fatigue, tiredness, weakness and myalgia, which may be attributed to changes in the muscles. Recent improvements in imaging technology, coupled with an increasing clinical interest, has started to ignite new interest in the area. This perspective discusses the rationale for using imaging, particularly ultrasound and MRI, for investigating muscle pathology involved in common inflammatory rheumatic diseases. The muscles associated with rheumatic diseases can be affected in many ways, including myositis—an inflammatory muscle condition, and myopathy secondary to medications, such as glucocorticoids. In addition to non-invasive visual assessment of muscles in these conditions, novel imaging techniques like shear wave elastography and quantitative MRI can provide further useful information regarding the physiological and biomechanical status of the muscle.

Monitoring and long-term management of giant cell arteritis and polymyalgia rheumatica.

Giant cell arteritis (GCA) is the most common type of primary vasculitis in Western countries. Polymyalgia rheumatica (PMR) is the second most common inflammatory rheumatic disease of the elderly after rheumatoid arthritis. Glucocorticoids are the cornerstone of treatment for GCA and PMR, which are interrelated diseases. Glucocorticoids are effective, but adverse effects occur in a high proportion of patients. Careful use of glucocorticoids and the application of preventive strategies can minimize these adverse effects. Possible long-term complications of GCA include aneurysm and stenosis of vessels, even in patients with apparently clinically inactive disease; acute blindness is rare during glucocorticoid treatment. In PMR, whether subclinical chronic inflammation can lead to long-term damage is less clear. Management of both GCA and PMR is hampered by the lack of universally accepted definitions of remission and other disease states, such as low disease activity or vessel damage without active disease. In this Review, we outline current evidence on the monitoring and long-term management of patients with GCA and PMR, including the tapering of treatment.

Methotrexate and The Lung in Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a common systemic rheumatic disease. While the most visible manifestation of RA is articular involvement, it is a true systemic disease with the potential to affect multiple organs. Methotrexate (MTX) is the most commonly used medication to treat RA. MTX pneumonitis (MTX-pneu) is a rare disease entity reported in MTX users. It usually develops acutely or subacutely in the first year of treatment. MTX-pneu presents with cough, dyspnoea, and often fever. Pre-existing lung disease is a major risk factor and the clinical diagnosis is based on MTX exposure, symptoms, and laboratory and imaging findings. Treatment involves MTX cessation and high-dose glucocorticoids. Interstitial lung disease (ILD) is a common manifestation of RA with clinical RA-ILD affecting up to 10% of patients. RA-ILD tends to be a more indolent process than MTX-pneu and frequently develops over years but can also be acute. Similar to MTX-pneu, RA-ILD presents with cough, dyspnoea, and often fever. Risk factors include age, male sex, disease activity, seropositivity, and smoking. Treatment is aimed at optimal control of RA disease and within this strategy there may be particular roles for rituximab, tocilizumab, and abatacept. Antifibrotics may also have a role. Given the distinct pathologies, the differentiation of these two entities is crucial. The treatment approach differs significantly and what is beneficial for one may be harmful for the other. In this paper, the authors discuss and contrast contemporary knowledge of MTX-pneu and RA-ILD.

Growth parameters of Turkish children with juvenile idiopathic arthritis

Purpose: Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in childhood which could results in growth retardation. With the present study, we aimed to investigate the growth parameters in Turkish children with JIA. Materials and Methods: Clinical and laboratory data, weight, height, and body mass index of 233 JIA patients were retrospectively collected from medical files. Growth parameters and z-scores were calculated by anthropometric references in Turkish children. The patients were diagnosed according to the International League of Associations for Rheumatology classification criteria.Results: The frequency of female patients was 59.2% (138). The mean age at diagnosis was 7.40±4.54 years, the mean age at the study time was 11.20±4.45 years. While mean initial visit weight and BMI z-scores were significantly improved at last visit, initial mean height z-score was significantly decreased. The frequency of short stature at last visit was 7.3% (number, 17). Acute phase reactants, including erythrocyte sedimentation rate, C-reactive protein levels were significantly lower at last visit than initial. Last visit growth parameters did not differ according age at diagnosis, disease duration and presence or absence of remission, relapses, corticosteroid usage, and biologic agent usage. Conclusion: Suppressing ongoing inflammation in JIA patients improves both weight and BMI z-scores of those patients, however, it may be insufficient to prevent short stature.

Biologics in juvenile idiopathic arthritis-main advantages and major challenges: A narrative review.

Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in childhood. The disease is divided in different subtypes based on main clinical features and disease course. Emergence of biological agents targeting specific pro-inflammatory cytokines responsible for the disease pathogenesis represents the revolution in the JIA treatment. Discovery and widespread usage of biological agents have led to significant improvement in JIA patients’ treatment, with evidently increased functionality and decreased disease sequel. Increased risk of infections remains the main discussion topic for years. Despite the slightly increased frequency of upper respiratory tract infections reported in some studies, the general safety of drugs is acceptable with rare reports of severe adverse effects (SAEs). Tuberculosis (TBC) represents the important threat in regions with increased TBC prevalence. Therefore, routine screening for TBC should not be neglected when prescribing and during the follow-up of biological treatment. Malignancy represents a hypothetical complication that sometimes causes hesitations for physicians and patients in its prescription and usage. On the other hand, current reports from the literature do not support the increased risk for malignancy among JIA patients treated with biological agents. A multidisciplinary approach including a pediatric rheumatologist and an infectious disease specialist is mandatory in the follow- up of JIA patients. Although the efficacy and safety of biological agents have been proven in different studies, there is still a need for long-term, multicentric evaluation providing relevant data.

Rheumatic diseases in childhood and adolescence: importance of early multi-professional care

Juvenile idiopathic arthritis (JIA) is the most common chronic inflammatory rheumatic disease in children. Both the disease, which is accompanied by pain and movement restrictions, and its usually complex, long-term therapy, are associated with burdens for those affected until adulthood. Impairments can affect many areas of life. Holistic care that considers the preferences and expressed needs of patients and their families is crucial in order to achieve the desired therapeutic goals of remission and the best possible quality of life. Since JIA begins in avery early phase of life, long-term consequences due to illness and therapy are of considerable importance.The approval of new substances that specifically intervene in the inflammatory process has fundamentally changed the treatment of JIA in recent years. Above all, early effective therapy makes adecisive contribution to an improved prognosis of JIA patients. Meanwhile, JIA patients enter adulthood with good everyday function and quality of life as well as less secondary damage and concomitant diseases, although only about half achieve stable therapy-free remission. In order to support the necessary transition into adult medicine, transition programmes have been developed to prepare young rheumatics for the new form of care and to prevent gaps in care and unfavourable outcomes. Last but not least, the recording of psychological factors is important in order to support the chronically ill in dealing with their illness and the resulting challenges, if necessary.

Intestinal microbiota and juvenile idiopathic arthritis: current understanding and future prospective.

Juvenile idiopathic arthritis (JIA) characterized by arthritis of unknown origin is the most common childhood chronic rheumatic disease, caused by both host genetic factors and environmental triggers. Recent evidence has mounted to focus on the intestinal microbiota, a potentially recognized set of environmental triggers affecting JIA development. Here we offer an overview of recently published animal and human studies that support the impact of intestinal microbiota in JIA. We searched PubMed for animal and human studies publications with the search terms "intestinal microbiota or gut microbiota" and "juvenile idiopathic arthritis or juvenile chronic arthritis or juvenile rheumatoid arthritis or childhood rheumatoid arthritis or pediatric rheumatoid arthritis". Several comparative studies have demonstrated that intestinal microbial alterations might be triggers in disease pathogenesis. Alternatively, a slice of studies has suggested environmental triggers in early life might disrupt intestinal microbial colonization, including cesarean section, formula feeding, and antibiotic exposure. Aberrant intestinal microbiota may influence the development of JIA by mediating host immune programming and by altering mucosal permeability. Specific microbial factors may contribute to the pathogenesis of JIA. Intensive studies, however, are warranted to investigate the causality between intestinal dysbiosis and JIA and the mechanisms behind these epidemiologic relationships. Studies are also needed to design the best interventional administrations to restore balanced intestinal microbial communities.

Serum homocysteine level in children with Juvenile Idiopathic Arthritis

Background: Juvenile Idiopathic Arthritis (JIA) is the most common chronic rheumatic disease of childhood and a leading cause of short and long-term disability. Abnormal level of serum homocysteine (Hcy) may be found in Juvenile idiopathic arthritis (JIA) patients. Some studies were done on serum homocyestine levels in children with JIA which showed conflicting results. So far, no study regarding the Hcy level in JIA patients was done in Bangladesh.&#x0D; Objectives: The study was aimed to assess the homocysteine level in children with different subtypes of JIA.&#x0D; Methods: It was a cross sectional and case control study. Fifty newly diagnosed cases of JIA attending the Pediatric Rheumatology clinic of Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, from January 2016 to March 2017 were included. Fifty age and sex matched controls were selected. Serum homocysteine levels were measured in both cases and controls.&#x0D; Results: Among JIA patients, 36% had high serum homocysteine (Hcy) level whereas 100% of controls had normal level. Mean hcy level was significantly (p&lt;0.05) higher among cases than controls. Significantly higher number and level of hyperhomocystaeinemia was found among JIA patients having duration of illness more than 1 year than duration less than 1 year. Mean homocysteine level of polyarticular RF positive cases was found as 14.38±3.79 µmol/L and that of SJIA was found as 13.0±4.66 µmol/L. When compared with homocysteine levels of control group these two groups had significantly higher homocysteine level.&#x0D; Conclusion: More than one third of JIA patients had hyperhomocysteinaemia. Mean hcy level of JIA cases was significantly higher than that of controls. Significant association of hyperhomocysteinaemia was present with duration of illness and certain types of JIA.&#x0D; Bangladesh Med Res Counc Bull 2020; 46(1): 12-16

P1703RESULTS OF RENAL TRANSPLANTATION IN PATIENTS WITH RHEUMATIC DISEASES

Abstract Background and Aims Rheumatic diseases often involve the kidneys and it might lead to chronic kidney disease (CKD). In its final stage it must be treated with renal replacement methods such as dialysis (hemodialysis or peritoneal dialysis) or renal transplantation. Kidney transplantation is the preferred and most cost-effective treatment for the end-stage renal disease, it offers a better quality of life than dialysis. The most common types of renal pathology in rheumatic diseases include glomerular (systemic lupus erythematosus), vascular (ANCA-associated vasculitides) and tubulointerstitial (goat) diseases. According to a research conducted in 2010 at the Minsk Rheumatological Department, 25% of patients had clinical or laboratory features of CKD. The aims were to reveal the most frequent rheumatic diseases affecting the kidneys and evaluate the post-transplant period in these patients. Method 94 medical case were studied retrospectively. All these patients had the end-stage renal disease with GFR of &amp;lt;15 ml/min/1.73m2 and underwent renal transplantation between January 2011 and September 2019. Results A retrospective study of 94 kidney transplant patients was conducted on renal transplantation centers in Belarus. Among the patients that underwent renal transplantation from January 2011 till September 2019, the percentage of recipients with rheumatic diseases was 3.64%. The majority of the recipients (52 %) were females. The mean age was 44.36 years (range, 16-78 years). Of the sample, 90% of kidney allografts were received from brain-dead donors, whereas only 10% of recipients got a new kidney from living-donors. Systemic lupus erythematosus was the most common causative disease in patients with rheumatic diseases (31 cases, 33%) followed by goat (28 cases, 30%) and secondary amyloidosis (17 cases, 18%) that complicated the course of rheumatoid arthritis and seronegative spondylarthritis. The remaining part of patients suffered from ANCA-associated vasculitides (10 cases, 10.6%), anti-glomerular basement membrane disease (6 cases, 6.4%), and single cases were represented by progressive systemic sclerosis and antiphospholipid syndrome (2%). In the post-transplant period, the most common complications were arterial hypertension (38%), anemia (20%), infectious diseases (27%), among them the most frequent were urinary tract infection (20%) and cytomegalovirus infection (7%). The 1-year allograft survival rate was 86%, the 5-year rate was about 82%. The main reasons for failed outcomes were acute renal allograft rejection, postoperative complications and infection. The patient survival rate after 1 and 5 years after transplantation was 93% and 86%, respectively. Infectious diseases (44%) such as nosocomial pneumonia, sepsis and cardiovascular disease (33%) are still the two most important reasons of death. Conclusion 1. The most common rheumatic diseases causing the end-stage renal disease are systemic lupus erythematosus (33%), goat (30%), rheumatoid arthritis, and seronegative spondylarthritis that lead to secondary amyloidosis (18%). 2. The 1-year allograft survival rate was 86%, the 5-year rate was about 82%, the patient survival rate after 1 and 5 years after transplantation was 93% and 86%, respectively. 3. The survival of patients with rheumatic diseases who underwent renal transplantation is comparable to patient survival after transplantation with another kidney pathology. 4. The main causes of death following renal transplantation are infectious and cardiovascular complications. Acute renal allograft rejection, postoperative complications, and infection are the main reasons of allograft failure.

THU0122 EFFECT OF THE METABOLIC SYNDROME ON RENAL FUNCTION DECLINE IN FOUR RHEUMATIC DISEASES: AN 8-YEAR LONGITUDINAL ANALYSIS

Background:Objectives:To study the effect of the metabolic syndrome (MetS) on renal function decline in four rheumatic diseases.Methods:Consecutive patients who fulfilled the ACR/SLICC criteria for systemic lupus erythematosus (SLE), EULAR/ACR criteria for rheumatoid arthritis (RA), ASAS criteria for spondyloarthritis (SpA) and the CASPAR criteria for psoriatic arthritis (PSA) were recruited in 2009/2010. At entry, patients recruited had measurement of body weight, height, waist circumference and blood pressure. MetS was defined by the updated joint consensus criteria, using the Asian criteria for central obesity, when ≥3 of the following were present: (1) waist ≥90cm in men or ≥80cm in women; (2) blood pressure ≥130/85mmHg or requiring therapy; (3) serum triglyceride level ≥1.7mmol/L; (4) serum HDL-chol ≤1.0mmol/L in men and 1.3mmol/L in women; and (5) fasting glucose ≥5.6mmol/L. Renal function of the participants was assessed by the 4-variable MDRD formula (eGFR). Patients were followed longitudinally for eGFR change. Change in eGFR was compared between those with and without the MetS at baseline. Regression analysis was performed for the effect of MetS on eGFR decline adjusted for other confounding factors.Results:1497 patients were studied (693 RA, 577 SLE, 121 SpA and 106 PSA). The age at entry was highest in RA (53.4±12.0 years) and lowest in SpA (39.0±11.9 years). Disease duration was longest in SLE (9.3±7.2 years) and shortest in PSA (3.6±3.2 years). MetS was present in 137 RA (20%), 85 SLE (15%), 13 SpA (11%) and 39 PSA (37%) patients. Patients were followed for 91.1±12.1 months. The mean decline of eGFR (ml/min/1.73m2) at last observation from baseline was 5.00±13.5 in RA, 4.16±11.6 in SpA, 3.95±12.3 in PSA and 8.93±16.4 in SLE (p=0.03; one-way ANOVA). The proportion of patients with eGFR decline by ≥10% was also greatest in SLE (41%) compared with RA (29%), SpA (24%) and PSA (25%) patients (p&lt;0.001). Among patients with SLE, a significantly more profound drop in eGFR over 8 years was observed in patients with the MetS at baseline (-17.8±26%) than those without (-7.6±18%; p=0.002). The difference in last eGFR between patients with and without the MetS was significant after adjustment for baseline eGFR, age and sex (65.5±32.2 vs 88.4±24.4 ml/min/1.73m2; p&lt;0.001). In a linear regression model, eGFR at last follow-up was significantly associated with the baseline eGFR (slope 0.72 SE 0.03; Beta 0.77; p&lt;0.001), renal involvement (slope -4.36 SE 1.30; Beta -0.08; p=0.001) and the MetS (slope -6.88 SE 1.86; Beta -0.09; p&lt;0.001). In patients with RA/SpA/PSA, eGFR also showed a greater trend of decline over time in those with MetS than without, but the difference did not reach statistical significance.Conclusion:Among patients with common rheumatic diseases, SLE showed the greatest decline in renal function over time. The presence of MetS in SLE significantly accelerated renal function decline over time independent of the presence of renal disease. The MetS also unfavorably affected eGFR in patients with inflammatory arthritis. A more detailed analysis on the causes of eGFR decline in individual diseases and a longer period of follow-up of the renal function is needed.Acknowledgments:NILDisclosure of Interests:None declared

OP0210 EFFICACY AND SAFETY OF SM03, A RECOMBINANT ANTI-HUMAN CD22 MONOCLONAL ANTIBODY IN CHINESE PATIENTS WITH RHEUMATOID ARTHRITIS: A PHASE II RANDOMIZED, DOUBLE-BLIND, MULTI-DOSE, PLACEBO-CONTROLLED STUDY

Background:Rheumatoid arthritis (RA) is a common chronic inflammatory rheumatic disease in China. SM03 is a novel chimeric monoclonal antibody (mAb) specific to the B cell restricted antigen CD22 developed for the treatment of rheumatoid arthritis (RA) and other B cell related immunological diseases.Objectives:We aim to evaluate the efficacy and safety of SM03 in patients with moderately-to-severely active RA in China.Methods:In this 24-week Phase II randomized, double-blind, multi-dose, placebo-controlled study, 156 patients were randomized with ratio of 1:1:1 to receive 3600mg cumulative dose of SM03 (group A, 600mg * 6 infusions at 0, 2, 4, 12, 14, and 16 week), 2400mg cumulative dose of SM03 (group B, 600mg*4 infusions at 0, 2, 12, and 14 week) and placebo (group C). All patients remained on background treatment of MTX. Efficacy and safety were assessed at weeks 4, 8, 12,16 and 24.The primary efficacy end point was the American College of Rheumatology 20% improvement criteria (ACR20) response rate at week 24.Safety profile was also assessed.Results:ACR20 response rates at 24-week were significant for group A (65.3%, p=0.002) and B (56.9 %, p=0.024) versus group C (34.0%). There is no significant difference in ACR20 between group A and B(Table 1 &amp; Fig 1). We did not observe significant difference in any adverse event (AE) among group A (35.3%), B (51.9%) and C (34.6%)(Table 2). In groups A and B, 13 (12.6%) patients reported treatment-related infection, and 5 (6.8%) patients were positive in anti-drug antibodies analysis. In group A (higher dose), 3.9% patient had AE of treatment-related infections. No patients reported treatment-related severe infection or any malignancies caused by treatment in groups A and B.Table 1.Summary of ACR/DAS EULAR Responses of Patients with RA to SM03 at Week 24ResponseGroup CPlacebo+MTX(n=47)Group A SM03600mg*6+MTX(n=49)Group B SM03600mg*4 +MTX(n=51)ACR 2034.0%65.3% *56.9% *ACR 5017.0%44.9%**29.4%ACR 704.3%18.4%***9.8%EULAR response good &amp; moderate40.4%75.5%^70.6%^EULAR response good12.8%30.6%^^15.7%Change of DAS28 from baseline-0.70-1.65^^^-1.38^^^DAS28≤3.214.9%30.6%19.6%DAS28&lt;2.68.5%18.4%5.9%Compared with group C(Placebo), results of group A and B were shown respectively*P=0.002, P=0.024; **P= 0.003; ***P= 0.03;^ P&lt;0.001, P=0.003; ^^ P=0.034; ^^^P=0.008, P=0.047Table 2.Profile of Adverse EventsAdverse event, N (%)Group C(N=52)Group A(N=51)Group B(N=52)Any AE18(34.6)18(35.3)27(51.9)AE-drug related7(13.5)5(9.8)8(15.4)AE-mild16 (30.8)15(29.4)24(46.2)AE-moderate2(3.8)2(3.9)3(5.8)AE-severe-1(2.0)-AE-leading to discontinuation-2(3.9)-Serious adverse event, SAE1(1.9)1(2.0)-AE-1stcycle(week 0-12)151322AE-2ndcycle(week 12-24)9914Fig 1.Percent of Patients Achieving ACR 20 Response by VisitConclusion:In Chinese patients with active RA, both 2400mg and 3600mg cumulative doseof SM03,in combination with MTX were efficacious and well tolerated. throughout the 24 weeks of treatment.Moreover, SM03 has demonstrated a good safety profile, especially in terms of treatment-related infection, malignancy and immunogenicity.

Imbalance Between Omega-6- and Omega-3-Derived Bioactive Lipids in Arthritis in Older Adults.

Elderly-onset rheumatoid arthritis (EORA) and polymyalgia rheumatica (PMR) are common rheumatic diseases in older adults. Oxylipins are bioactive lipids derived from omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids (PUFAs) that serve as activators or suppressors of systemic inflammation. We hypothesized that arthritis symptoms in older adults were related to oxylipin-related perturbations. Arthritis in older adults (ARTIEL) is an observational prospective cohort with 64 patients older than 60 years of age with newly diagnosed arthritis. Patients' blood samples at baseline and 3 months posttreatment were compared with 18 controls. A thorough clinical examination was conducted. Serum oxylipins were determined by mass spectrometry. Data processing and statistical analysis were performed in R. Forty-four patients were diagnosed with EORA and 20 with PMR. At diagnosis, EORA patients had a mean DAS28CRP (Disease Activity Score 28 using C-reactive protein) of 5.77 (SD 1.02). One hundred percent of PMR patients reported shoulder pain and 90% reported pelvic pain. Several n-6- and n-3-derived oxylipin species were significantly different between controls and arthritis patients. The ratio of n-3/n-6 PUFA was significantly downregulated in EORA but not in PMR patients as compared to controls. The top two candidates as biomarkers for differentiating PMR from EORA were 4-HDoHE, a hydroxydocosahexaenoic acid, and 8,15-dihydroxy-eicosatrienoic acid (8,15-diHETE). The levels of n-3-derived anti-inflammatory species increased in EORA after treatment. These results suggest that certain oxylipins may be key effectors in arthrtis in older adults and that the imbalance between n-6- and n-3-derived oxylipins might be related to pathobiology in this population.