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30911335 "Come and live with my feet and you'll understand" - a qualitative study exploring the exp 2019 BACKGROUND: Foot pain and deformity are common in people with rheumatoid arthritis (RA). Previous research has identified that women with RA seek retail footwear to alleviate their foot problems. The specific footwear features that women with RA require, and what would help them to find shoes that meet these requirements, are unknown. This study aimed to determine the factors that influence the choice of appropriate retail footwear by women with RA. METHOD: An overarching qualitative approach was taken, using reflexive thematic analysis of conversational style interviews. The interviews explored experiences and use of retail footwear in 20 women with RA. The interviews were digitally recorded transcribed verbatim and analysed using a reflexive thematic framework. RESULTS: Women with RA sought retail footwear which had adequate cushioning, width, a flexible sole, lightweight, were made from breathable materials and were easy to put on and take off. However, this choice was driven by the need for comfort, cost and usability, with aesthetics being less of a priority. Despite having opinions on what criteria they felt that they needed, these women did not feel empowered to make good choices about purchasing retail footwear for symptomatic relief. Furthermore, they did not receive the necessary support from podiatrists and shoe shop staff. CONCLUSION: Women with RA have clear ideas about what features a retail shoe should have to achieve comfort. There is a constant compromise between achieving comfort and their feelings about their appearance and how they feel others perceive them. Women with RA describe negative experiences with shoe shop assistants and podiatrists leading to poor footwear choices. Both retail staff and podiatrists need increased understanding about the particular problems that women with RA experience.
31948603 Incidence and effect of insulin resistance on progression of atherosclerosis in rheumatoid 2019 Dec BACKGROUND: The continued atherosclerotic risk in rheumatoid arthritis (RA) has been inadequately explained by conventional factors. Chronic inflammation and endothelial activation seems responsible for developing insulin resistance (IR). The study was aimed to assess the role of inflammation and endothelial activation causing IR in long term RA patients leading to increased atherosclerotic risk. METHODS: Fifty (25 long-duration and 25 short-duration) RA patients and twenty-three healthy controls were recruited excluding potential confounding co-morbidities. Fasting insulin, proinflammatory cytokines, endothelial stress markers and adipokines were quantified by ELISA. Homeostasis Model Assessment (HOMA)-IR calculated using glucose and insulin values. Atherosclerotic indices were measured using ultrasound. RESULTS: Lipid profile was comparable among groups. Mean carotid intima media thickness (cIMT) was significantly higher in both RA groups (p = 0.0062) compared to controls. HOMA-IR was significantly higher in long-duration RA (p = 0.005); it showed significant associations with DAS 28 (p = 0.01) and hsCRP (p = 0.03) in this subset. Mean cIMT for short-duration RA (p = 0.02) and long-duration RA (p = 0.0006) respectively was also significantly associated with HOMA-IR. Pro-inflammatory markers like TNF-α, resistin and leptin were highest in long-duration RA, higher in short-duration RA when compared to control group respectively. HOMA-IR was significantly dependent on TNF-α (p = 0.008), resistin (p = 0.031), leptin (p = 0.0054). Mean cIMT showed association with all parameters mainly with TNF-α (p = 0.001), iNOS (p = 0.001), resistin (p = 0.008) and leptin (p = 0.04). CONCLUSIONS: Persistent inflammation leads to altered adipokine secretion promoting IR in RA patients with long disease duration. Treatment with conventional disease modifying anti-rheumatic drugs (DMARDs) is incomplete to control chronic inflammation and limit progression of atherosclerosis.
30341703 Remission rate and predictors of remission in patients with rheumatoid arthritis under tre 2019 Mar This systematic review and meta-analysis aim to evaluate the remission rate of patients with rheumatoid arthritis (RA) in real-world studies and to summarize potential predictors of remission in RA. Studies reporting remission rate in patients with RA were searched from MEDLINE, EMBASE, and Scopus databases. Two reviewers independently assessed all studies according to eligibility criteria and extracted data. Generally, observational studies reporting remission rate in adult (≥ 18 years) patients with RA were included. Quality assessments were performed using the Newcastle-Ottawa Scale. Pooled analyses of remission rate were conducted using a random-effects model and data were analyzed in subgroups to identify potential source of heterogeneity. Sensitivity analyses were performed by serially excluding each study. Potential predictors of remission were summarized. Thirty-one studies with ~ 82,450 RA patients in total were included. Using the DAS28 remission criteria, the pooled 3-, 6-, 12-, and 24-month remission rates were 17.2%, 16.3%, 21.5%, and 23.5%, respectively. Subgroup analyses showed that 11.7% and 13.8% of TNFi inadequate responders reached remission after 6- and 12-month use of non-TNFi biologics. Predictors of remission included male, higher education level, and lower baseline disease activity, while initial use of corticosteroids was negative predictors of remission. Sustained remission was rare regardless of different criteria used. Remission was a reachable target in real-world studies, while attention should also be paid to achieve sustained remission.
31430907 Galectin-9 Is a Possible Promoter of Immunopathology in Rheumatoid Arthritis by Activation 2019 Aug 19 The aetiology of rheumatoid arthritis (RA) is unknown, but citrullination of proteins is thought to be an initiating event. In addition, it is increasingly evident that the lung can be a potential site for the generation of autoimmune triggers before the development of joint disease. Here, we identified that serum levels of galectin-9 (Gal-9), a pleiotropic immunomodulatory protein, are elevated in RA patients, and are even further increased in patients with comorbid bronchiectasis, a lung disease caused by chronic inflammation. The serum concentrations of Gal-9 correlate with C-reactive protein levels and DAS-28 score. Gal-9 activated polymorphonuclear leukocytes (granulocytes) in vitro, which was characterized by increased cytokine secretion, migration, and survival. Further, granulocytes treated with Gal-9 upregulated expression of peptidyl arginine deiminase 4 (PAD-4), a key enzyme required for RA-associated citrullination of proteins. Correspondingly, treatment with Gal-9 triggered citrullination of intracellular granulocyte proteins that are known contributors to RA pathogenesis (i.e., myeloperoxidase, alpha-enolase, MMP-9, lactoferrin). In conclusion, this study identifies for the first time an immunomodulatory protein, Gal-9, that triggers activation of granulocytes leading to increased PAD-4 expression and generation of citrullinated autoantigens. This pathway may represent a potentially important mechanism for development of RA.
31822530 Meningeal rheumatoid nodules in a 55-year-old man presenting with chronic headaches and oc 2019 Dec 9 Rheumatoid arthritis (RA) is a multisystem inflammatory disease which can involve many organ systems including the central nervous system (CNS). Though not very common, the results can be severely debilitating. The spectrum of the CNS involvement includes meningitis, encephalitis and occasionally rheumatoid nodules. Its presentation is variable, though very rarely it can present as focal neurological deficits. Imaging can be suggestive, but diagnosis usually requires tissue biopsy. Treatment consists of high-dose steroids and immunosuppressants. We describe the case of a 55-year-old male patient with a history of RA presenting with a third nerve palsy and headache who was found to have rheumatoid nodules on biopsy. CNS involvement in RA should be considered in anyone with rheumatoid arthritis who presents with focal neurological deficits, though infections and space-occupying lesions should also be ruled out.
30993918 Silicon intake and plasma level and their relationships with systemic redox and inflammato 2019 Nov BACKGROUND: The nutritional significance of silicon for the human body is highlighted by a continually growing body of evidence. In conditions of excessive reactive oxygen species and upregulated immune response, silicon has been observed to provide benefits, but its role in redox and inflammatory status has not yet been examined in rheumatoid arthritis (RA). OBJECTIVES: The aim of this study was to assess the relationship of silicon intake and plasma level to systemic indices of redox status and inflammation in patients with RA. MATERIAL AND METHODS: Silicon intake and plasma levels were measured in 115 RA subjects and 129 control subjects. Serum antioxidant and oxidant levels, antioxidant enzyme activity, and albumin, uric acid, TBARS, hs-CRP, and IL-6 levels were measured and compared to the intake and plasma levels of silicon. RESULTS: Silicon intake and plasma silicon levels were higher in RA subjects than in the controls. In the RA group, a generally favorable correlation to redox and inflammatory markers was found for silicon in diet and in plasma; however, albumin level, smoking status, and gender interfered with these results. In the control subjects, a significant relationship was observed only between plasma silicon and non-enzymatic markers of redox status. CONCLUSIONS: There are suggestions of silicon's involvement in managing redox and inflammatory status in RA, though further studies are warranted.
31413866 Six-month prospective trial in early and long-standing rheumatoid arthritis: evaluating di 2019 INTRODUCTION: Standardised scoring systems for rheumatoid arthritis (RA) joint disease activity include Larsen score for radiographs, rheumatoid arthritis magnetic resonance imaging score (RAMRIS) for MRI and using the European League Against Rheumatisms-Outcome Measures in Rheumatology (EULAR-OMERACT) score for ultrasound (US) images. The aim of this prospective study was to investigate the relationship between histological synovitis and radiological synovitis, assessed by conventional X-ray, US and MRI of the wrist radiocarpal joint. METHODS: 20 patients with treatment naive early RA (ERA) and 20 with long-standing RA (LRA) were enrolled in a 6-month prospective study. Patients with RA underwent US-guided synovial biopsy, X-ray and US of the wrist at enrolment and 6 months. MRI at baseline and also at 6 months for the ERA group, and scored with the RAMRIS system. X-ray was scored by Larsen score and US by the EULAR-OMERACT system. Synovial biopsy inflammation was determined by the Krenn score. RESULTS: In the ERA group at baseline, Krenn score was correlated strongly with both US combined score (r = 0.77 p < 0.001) and MRI synovitis score (r = 0.85 p < 0.001), while uncorrelated at 6 months. In the LRA group at baseline, these scores correlated strongly (r = 0.83, p < 0.001) to moderately (r = 0.61, p = 0.002), and persisted at 6 months for US score (r = 0.81 p < 0.001). For all patients with RA, change in Krenn score between baseline and 6 months was correlated with both change in US combined score (r = 0.65, p < 0.001) and change in MRI synovitis score (r = 0.50, p = 0.03). CONCLUSION: The MRI RAMRIS synovitis score and EULAR-OMERACT US scoring system are sensitive measures of histological synovitis in LRA and ERA. After 6 months, this correlation persists in the established RA group, but not in the ERA group. Overall, decreases in MRI/US synovitis are associated with reductions in histological synovitis. The study validates the use of MRI RAMRIS and EULAR-OMERACT US scores as surrogate markers of histological synovitis in established RA and early untreated RA.
30949174 Lymphatic Function in Autoimmune Diseases. 2019 Lymphatic vessels are critical for clearing fluid and inflammatory cells from inflamed tissues and also have roles in immune tolerance. Given the functional association of the lymphatics with the immune system, lymphatic dysfunction may contribute to the pathophysiology of rheumatic autoimmune diseases. Here we review the current understanding of the role of lymphatics in the autoimmune diseases rheumatoid arthritis, scleroderma, lupus, and dermatomyositis and consider the possibility that manual therapies such as massage and acupuncture may be useful in improving lymphatic function in autoimmune diseases.
31271042 Bubbles in the Box: Recurrent Pneumothorax From Bronchopleural Fistula in Rheumatoid Arthr 2019 Jan When considering rheumatoid arthritis (RA)-associated pulmonary diseases, interstitial lung disease and pleural disease are the most common RA-associated pulmonary manifestations while spontaneous pneumothorax and bronchopleural fistula (BPF) are among the extremely rare ones. To the best of our knowledge, all the previous reports of RA-associated BPFs were attributed to peripherally located pulmonary nodules that necrotized, burst into the pleural cavity, and eventually lead to the fistula formation. However, we hereby present the first case of BPF in an RA patient that formed in the absence of any underlying rheumatic pulmonary nodules. Additionally, our patient was on chronic methotrexate therapy, and there are no data in the literature that suggest methotrexate-induced parenchymal lung disease can predispose to BPF formation. Our report is the first to introduce a probe to further investigate this association.
31669381 PTPN22 1858 C/T polymorphism is associated with alteration of cytokine profiles as a poten 2019 Dec INTRODUCTION: Rheumatoid arthritis (RA) is one of the most common prevalent autoimmune diseases. The 1858 C/T (rs2476601) single nucleotide polymorphism (SNP) within the PTPN22 gene has been associated with susceptibility to inflammatory based diseases in several populations. It is implicated that altered cytokine production has a potential pathogenic role in the development of RA. The aim of this work was to analyze the association of 1858 C/T PTPN22 polymorphism in RA patients with cytokine profiles. MATERIALS AND METHODS: This study was performed on 120 RA patients who were referred to the Rheumatology Research Centre, Shariati Hospital (Tehran, Iran), and 120 healthy controls. Genomic DNA was extracted and genotyped for 1858 C/T PTPN22 gene SNP using the PCR-RFLP technique. Serum levels of IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ as well as Anti-CCP and RF was measured by ELISA method. RESULTS: Results showed that 1858 C/T PTPN22 SNP significantly (P =  0.007, OR = 2.321, 95% CI = 1.063-5.067) associated with RA. The 1858 T allele frequency was also significantly increased in RA patients in comparison to the controls (P =  0.008, OR = 3.583, 95% CI = 1.3-9.878). Our data demonstrated a significant reduction of IL-4 and IL-10 in PTPN22 1858C/T compared to 1858C/C RA patients. In addition, upregulation of IL-6, IFN-γ, and TNF-α was observed in PTPN22 1858C/T vs. 1858C/C RA patients. DISCUSSION: Our findings implicate altered cytokine profiles as a possible pathogenic mechanism by which the 1858 T allele may contribute to the progress of RA.
31130229 Association of Changes in Anticitrullinated Protein Antibody Levels With Resource Use and 2019 Jun PURPOSE: Anticitrullinated protein antibody (ACPA) concentration, beyond ACPA positivity, is indicative of more aggressive radiographic progression in patients with rheumatoid arthritis (RA). However, there is limited information on the association of changes in ACPA with resource use measures and/or disease activity measures. We evaluate associations between changes in levels of ACPA and outcomes, including durable medical equipment (DME) use, hospitalizations, and disease activity, in patients with established RA. METHODS: Patients from the Brigham and Women's Hospital Rheumatoid Arthritis Sequential Study who had ACPA measurements at baseline and month 12 were included. Changes in ACPA levels from baseline to month 12 were categorized as a decrease (<-10%), no change (-10% to +10%), or increase (>+10%). DME use and hospitalizations were assessed twice yearly using patient questionnaires; disease activity was assessed annually. Binary multivariate logistic regression was used to analyze the association between changes in ACPA levels and DME use and hospitalizations; linear regression was used to assess the association with disease activity. FINDINGS: Of 840 patients included in the analysis, 291 (34.6%), 266 (31.7%), and 283 (33.7%) had a decrease, no change, or increase in ACPA levels, respectively. A decrease in ACPA levels was associated with a reduction in DME use (adjusted odds ratio [aOR] = 0.64; 95% CI, 0.44-0.93; P = 0.02) and hospitalizations (aOR = 0.62; 95% CI, 0.41-0.95; P = 0.03) versus no change or increase. Adjusted mean changes in disease activity score in 28 joints (C-reactive protein), total and swollen joint counts, and pain scores were significantly greater in patients with decreased ACPA levels versus those with no change or increase (P < 0.05). IMPLICATIONS: Among patients with RA, reductions in ACPA levels of >10% were associated with reductions in DME use, hospitalizations, and disease activity. ClinicalTrials.gov identifier: NCT01793103.
27028097 The relation between ischemia modified albumin levels and carotid intima media thickness i 2019 Jan BACKGROUND: Cardiovascular diseases, among which atherosclerotic heart disease, are known to be one of the most important mortality and morbidity causes in patients with rheumatoid arthritis (RA). Ischemia modified albumin (IMA) is a potential marker that can be used to assess atherosclerosis-related myocardial ischemia. Another frequently used marker for the assessment of atherosclerotic lesions is the carotid intima media thickness (CIMT). AIM: To evaluate the role that IMA has on atherosclerosis development and its clinical usability in patients with RA, by assessing the values of IMA and CIMT. METHODS AND MATERIALS: Our prospective study was conducted between June 2012 and March 2013 at the Rheumatology Department of Necmettin Erbakan Meram Medical School, Turkey. Fifty-two RA patients, diagnosed according to the 1987 criteria of the American College of Rheumatology, and an age- and sex-matched control group of 46 healthy subjects were included in this study. RESULTS: No significant difference was detected between the groups with respect to age, sex and body mass index. In the patient group the IMA and CIMT values were found to be 0.37 ± 0.12 absorbance units (ABSU) and 0.80 ± 0.22 mm, respectively, while in the control group they were 0.31 ± 0.11 ABSU and 0.51 ± 0.18 mm, respectively. The IMA and CIMT values were significantly higher in the patient group (P = 0.022 and P < 0.0001, respectively). A positive correlation was found between IMA, CIMT and Disease Activity Score of 28 joints (P = 0.016 and P = 0.002, respectively). CONCLUSION: Since the values of IMA were higher in the patient group compared to controls and because of its correlation with CIMT, we suggest the use of IMA as an early marker of atherosclerosis in RA patients.
30803720 Anti-nuclear antibody development is associated with poor treatment response to biological 2019 Oct BACKGROUND: It has been well known that TNF-α inhibitor (TNFi) treatment for patients with rheumatoid arthritis (RA) is associated with anti-nuclear antibody (ANA) development. We previously reported that ANA development was associated with poor outcomes of infliximab (IFX) treatment (1). However, no replication studies have been reported to date. In addition, whether the findings are true to general biological disease-modifying anti-rheumatic drugs (bDMARDs) is uncertain. METHODS: To evaluate an association between treatment response and ANA development during bDMARDs treatment in RA and to analyze correlates of ANA development, Japanese RA patients treated with (n = 657) or without (n = 211) bDMARDs as a first line bDMARD were enrolled from a single center cohort. ANA was measured by an indirect immunofluorescence assay at multiple time points of treatment. We analyzed associations between ANA development and insufficient response to treatment. Correlates of ANA development were also analyzed. RESULTS: ANA development (≥2 times baseline levels) at 3 months and at 6-12 months after bDMARDs initiation were significantly associated with insufficient response at 3-12 months (odds ratio (OR)=3.51, p = 0.020) and at 12-24 months (OR = 3.16, p = 0.038), respectively. The associations remained significant after conditioning on the use of each bDMARD. The use of IFX (OR = 6.24, p < 0.001) was a risk for ANA development, and other TNFi showed the same tends as infliximab. On the other hand, non-TNFi bDMARDs were not associated with ANA development. CONCLUSIONS: ANA development could be a marker of poor treatment response in RA patients undergoing bDMARDs treatment. Undefined factors might influence ANA development and subsequent poor bDMARDs outcome in RA.
30880318 Study of correlation of level of expression of Wnt signaling pathway inhibitors sclerostin 2019 This study was done with aim to assess the serum sclerostin and dickkopf-1 (DKK-1) level in patients of rheumatoid arthritis (RA) and to correlate their level with disease activity and bone mineral density. Fifty patients of RA and equal age and sex matched healthy controls were included in the study. Patients were evaluated clinically and investigated with routine blood tests along with rheumatoid factor (RF), anti-citrullinated protein antibody (anti-CCP(2)), radiographs and bone mineral density (BMD). Serum sclerostin and DKK-1 levels of both cases and controls was assayed by using enzyme-linked immunosorbent assay (ELISA) assay [RayBio(®), Georgia, USA with coefficient of variation percent (CV %), < 10%] and compared with disease activity and bone mineral density. Disease activity was measured by Disease Activity Score 28 (DAS28) along with Modified Health Assessment Questionnaire (MHAQ) score. Mean serum sclerostin and DKK-1 was significantly higher in study group as compared to control group. Serum sclerostin showed significant correlation with disease activity scores (DAS score and MHAQ score), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level. Serum sclerostin at level of 394 pg/mL was found to have diagnostic significance with sensitivity of 100% and specificity of 90%. DKK-1 level shows significantly positive correlation with larson score which denotes radiological progression (r value 0.468; p value 0.001). More studies with larger sample size of RA patients are needed for better determination of the role of sclerostin and DKK-1 in RA. Also, the correlation of these and other bone turn over markers will help decipher their role with disease progression in RA patients.
30204896 Autoantibody status is not associated with early treatment response to first-line methotre 2019 Jan 1 OBJECTIVES: In RA, the relationship between autoantibody status and treatment response to MTX remains unclear. We investigated the association between autoantibody status and early remission in newly diagnosed RA patients treated with MTX using real-world data. METHODS: RA-patients initially treated with MTX were selected from an international observational database (METEOR). Patients were stratified into autoantibody-positive (RF- and/or ACPA-positive) or autoantibody negative (RF- and ACPA-negative). The effect of autoantibody status on the chance of achieving remission within 3 to 6 months was analysed using Cox-proportional hazards regression. RESULTS: Data from 1826 RA patients were available for analysis. DAS remission was achieved in 17% (318/1826). This was similar in autoantibody-positive [17% (282/1629)] and -negative patients [18% (36/197)]. Hence, autoantibody positivity was not associated with remission [hazard ratio (HR) 0.89, 95% CI 0.57, 1.38]. Similar findings were found when stratified for MTX monotherapy (HR 0.75, 95% CI 0.41, 1.37) or combination treatment (HR 0.76, 95% CI 0.37, 1.54). Good physical function (HAQ < 0.5) was achieved in 33% (530/1590) of all patients. Autoantibody-positivity was also not associated with HAQ < 0.5 (HR 1.05, 95% CI 0.71, 1.57). CONCLUSION: Autoantibody status is not associated with early remission in newly diagnosed RA-patients receiving MTX. This indicates that MTX is effective as an initial treatment strategy regardless of autoantibody status.
32800021 Care-seeking pathways, care challenges, and coping experiences of rural women living with 2019 Jul 30 AIM: The aim of the study was to explore the care-seeking pathway of rural women living with rheumatoid arthritis (RA) and attending a tertiary health-care facility in Odisha, India. BACKGROUND: RA is the third leading chronic health condition and causes severe pain and immense psychosocial stress. The prevalence of RA is three to four times higher in women than in men. Furthermore, in India, women delay care seeking due to the prevailing sociocultural norms. Women report more severe symptoms and greater disability; however, there is a lack of information on their care-seeking pathways. METHOD: We conducted 113 in-depth interviews among RA patients those who visited specialists at the outpatients' Department of Rheumatology, SCB Medical College Hospital, a tertiary care hospital in Cuttack, Odisha, India. The grounded theory approaches were used for data analysis. FINDINGS: The key findings included physical pain and psychosocial stress in relation to RA, cultural issues in relation to RA, mapping of the health-care providers for RA, the first point of cares and changes in care-seeking pathways, the perceived challenge for seeking health-care, and coping strategies of patients and social supports. This study explored that the RA patients seek care from multiple providers - untrained, trained and specialist without any gatekeeping. However, the primary health centers were the first point of care for maximum patients due to accessibility and affordability. Furthermore, follow-up care is significant to prevent complication among RA patients; the primary health centers are the gateway for keeping RA patients. Hence, the availability of RA trained providers at primary health center including interprofessional care, such as physiotherapy providers, and proper referral system is essential to convalesce care-seeking pathways.
30677786 Outcomes of Minimally Invasive Oblique Lumbar Interbody Fusion in Patients with Lumbar Deg 2019 May PURPOSE OF STUDY:  Standard treatment protocols for lumbar degenerative lesions in the setting of rheumatoid arthritis (RA) are lacking. The purpose of this study was to evaluate the clinical and radiologic outcomes of minimally invasive oblique lumbar interbody fusion (MI-OLIF) in RA patients having degenerative lumbar spine lesions. METHODS:  This was a retrospective hospital-based case series (evidence level 4). Eight patients with degenerative lumbar disease with significant back pain and neurologic claudication underwent MI-OLIFwith polyetheretherketone cage insertion and posterior pedicle screw instrumentation. The clinical outcomes were measured by the numerical rating scale (NRS) for back and leg pain and the Oswestry Disability Index (ODI), and radiologic outcomes were studied on radiographs, computed tomography, and magnetic resonance imaging. Minimum follow-up duration was 1 year. RESULTS:  Mean NRS results for back and leg pain preoperatively were 6.3 and 7.1 that improved to 2.6 and 2 for back and leg pain, respectively, at last follow-up. The mean ODI scores preoperatively were 58.02 that improved to 39.06 at last follow-up. All patients had good functional outcomes, good fusion rates, and were able to continue their activities of daily living without much disability at last follow-up. CONCLUSION:  MI-OLIF in patients with symptomatic lumbar spine degenerative lesions with RA seems to provide good short-term clinical and radiologic outcomes.
30767874 Predictive value of ex-vivo drug-inhibited cytokine production for clinical response to bi 2019 May OBJECTIVES: To investigate ex-vivo drug-inhibited cytokine production before the start of a biological DMARD (bDMARD) as predictor of treatment response in rheumatoid arthritis (RA). METHODS: In a prospective RA cohort study [BIO-TOP], blood samples were obtained from patients before the start of a bDMARD (abatacept, adalimumab, etanercept, rituximab or tocilizumab). Peripheral blood mononuclear cells were pre-incubated for 1 hour with the therapeutic in-vivo concentration of the bDMARD and stimulated for 24 hours with heat-killed Candida albicans or Pam3Cys. Concentrations of IL-1β, IL-6, TNFα, IL-17 and IFNγ were determined by ELISA. EULAR response (good vs. moderate/no) was assessed at month 6. Area under the receiver operating characteristic curves (AUCs) were generated to evaluate the predictive value of baseline characteristics and ex-vivo cytokine production (including stimulated cytokine concentrations and absolute changes after inhibition by a bDMARD). Logistic prediction models were created to assess the added value of potential cytokine predictors. RESULTS: 277 RA patients were included with 330 blood samples. Good response was reached in 39% of the cases. DAS28-CRP was predictive for response to adalimumab (AUC 0.70, 95%CI 0.57-0.83), etanercept (AUC 0.68, 95%CI 0.58-0.78) and rituximab (AUC 0.76, 95%CI 0.65-0.86). ACPA was modestly predictive for response to abatacept (AUC 0.63, 95%CI 0.52-0.75). In the ex-vivo analysis, 4 of 64 (6%) tests showed some predictive value but these had no added value to clinical factors routinely measured in RA, such as DAS28-CRP. CONCLUSIONS: Ex-vivo inhibition of cytokine production by bDMARDs is unable to help prediction of treatment response to bDMARDs in RA.
30499417 Body Mass Index Impact on Disease Activity, Clinical and Sonographic Remission Rates in Pa 2019 AIM: To investigate the impact of body mass index (BMI) on clinical disease activity indices and clinical and sonographic remission rates in patients with rheumatoid arthritis (RA). PATIENTS AND METHODS: Sixty-three patients with RA were categorized according to BMI score into three groups: normal (BMI<25), overweight (BMI 25-30) and obese (BMI≥30). Thirty-three of them were treated with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), and 30 with biologic DMARDs (bDMARDs). Patients underwent clinical and laboratory assessment and musculoskeletal ultrasound examination (MSUS) at baseline and at 6 months after initiation of therapy. We evaluated the rate of clinical and sonographic remission (defined as Power Doppler score (PD) = 0) and its correlation with BMI score. RESULTS: In the csDMARDs group, 60% of the normal weight patients reached DAS28 remission; 33.3% of the overweight; and 0% of the obese patients. In the bDMARDs group, the percentage of remission was as follows: 60% in the normal weight subgroup, 33.3% in the overweight; and 15.8% in the obese. Within the csDMARDs treatment group, two significant correlations were found: BMI score-DAS 28 at 6th month, rs = .372, p = .033; BMI score-DAS 28 categories, rs = .447, p = .014. Within the bDMARDs group, three significant correlations were identified: BMI score-PDUS at sixth month, rs = .506, p =.004; BMI score-DAS 28, rs = .511, p = .004; BMI score-DAS 28 categories, rs = .592, p = .001. Sonographic remission rates at 6 months were significantly higher in the normal BMI category in both treatment groups. CONCLUSION: BMI influences the treatment response, clinical disease activity indices and the rates of clinical and sonographic remission in patients with RA. Obesity and overweight are associated with lower remission rates regardless of the type of treatment.
30414892 Decrease in 14-3-3η protein levels is correlated with improvement in disease activity in 2019 Mar 14-3-3η protein is a proinflammatory mediator that may represent a novel diagnostic and prognostic biomarker for rheumatoid arthritis (RA). We assessed the correlation between changes in serum 14-3-3η levels and changes in clinical disease activity measures in RA patients treated with Tofacitinib (TOF). Paired serum samples from 35 patients with RA were obtained at baseline and 5 months after the initiation of treatment with TOF. The levels of 14-3-3η were measured by JOINT stat 14-3-3η ELISA test kits (Augurex Life Sciences Corp.). The cut-off was defined as 0.19 ng/ml. 14-3-3η positivity was found in 57% of the patients at baseline and in 37% of the patients after 5 months of treatment. Mean ± SD baseline 14-3-3η levels [4.92 ± 8.86 ng/ml] were significantly higher (p < 0.005) than 14-3-3η levels following treatment [1.97 ± 4.59 ng/ml]. A statistically significant improvement (p < 0.001) of CDAI, SDAI, DAS4ESR and DAS4CRP was achieved after 5 month of treatment. Decrease in 14-3-3η protein levels was highly correlated with improvement in DAS4ESR (r = 0.50, p < 0.01), DAS4CRP (r = 0.46, p < 0.01) and ESR (r = 0.36, p = 0.03) and moderately correlated with improvement in CDAI (r = 0.32, p = 0.065) and SDAI (r = 0.33, p = 0.051). The correlation between decrease in 14-3-3η levels and improvement in DAS4ESR remained significant in a partial correlation analysis controlling for ESR (r = 0.39, p = 0.02). This study demonstrates that in RA patients who were treated with TOF, decrease in 14-3-3η levels is correlated with improvement in clinical disease activity parameters. The 14-3-3η protein may serve as an objective biomarker for monitoring of TOF therapy response.