tbuckley/cabot-search huggingface dataset:
Benefit–Risk Profile of Sphingosine-1-Phosphate Receptor Modulators in Relapsing and Secondary Progressive Multiple Sclerosis
Authors: Giancarlo Comi, Hans-Peter Hartung, Rajesh Bakshi, Ian M. Williams, Heinz Wiendl
Journal: Drugs (2017)

Since the approval of fingolimod, several selective sphingosine-1-phosphate receptor modulators have entered clinical development for multiple sclerosis. However, side effects can occur with sphingosine-1-phosphate receptor modulators. By considering short-term data across the drug class and longer term fingolimod data, we aim to highlight the potential of sphingosine-1-phosphate receptor modulators in multiple sclerosis, while offering reassurance that their benefit–risk profiles are suitable for long-term therapy. Short-term fingolimod studies demonstrated the efficacy of this drug class, showed that cardiac events upon first-dose administration are transient and manageable, and showed that serious adverse events are rare. Early-phase studies of selective sphingosine-1-phosphate receptor modulators also show efficacy with a similar or improved safety profile, and treatment initiation effects were reduced with dose titration. Longer term fingolimod studies demonstrated sustained efficacy and raised no new safety concerns, with no increases in macular edema, infection, or malignancy rates. Switch studies identified no safety concerns and greater patient satisfaction and persistence with fingolimod when switching from injectable therapies with no washout period. Better outcomes were seen with short than with long washouts when switching from natalizumab. The specific immunomodulatory effects of sphingosine-1-phosphate receptor modulators are consistent with the low observed rates of long-term, drug-related adverse effects with fingolimod. Short-term data for selective sphingosine-1-phosphate receptor modulators support their potential effectiveness in multiple sclerosis, and improved side-effect profiles may widen patient access to this drug class. The long-term safety, tolerability, and persistence profiles of fingolimod should reassure clinicians that sphingosine-1-phosphate receptor modulators are likely to be suitable for the long-term treatment of multiple sclerosis.
AB1244-HPR Guided self-management for patients with rheumatic inflammatory diseases and fatigue – a pilot project
Authors: E Fjerstad, RH Moe, S Nymo, T Berge
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Fatigue is reported to be a common symptom in people with inflammatory rheumatic diseases. It is a complex symptom, characterized by an individual interplay of biopsychosocial factors that has been associated with factors like inflammation, deconditioning, sleep problems, decreased function, pain and psychosocial factors like depression. <h3>Objectives</h3> The main objective was to contribute to improved coping and quality of life in people with inflammatory rheumatic disease and fatigue. Cognitive therapy is one of the common psychological interventions used in the rehabilitation of people with rheumatic diseases and fatigue. The current intervention was developed as a supplement to medical treatment to strengthen coping and quality of life, and reducing fatigue, depression and pain. <h3>Methods</h3> People with inflammatory rheumatic diseases and fatigue were recruited for 6–9 sessions of cognitive therapy sessions, in addition to treatment as usual at a rheumatology outpatient clinic in Norway. The intervention aimed at reducing fatigue, depression and pain, consisted of four main elements; understanding fatigue, assessment and activity planning, mental and cognitive self-help skills. The project was developed, and data collected at the rheumatology outpatient clinic at Diakonhjemmet Hospital in 2014–2016. <h3>Results</h3> This pilot project recruited 40 people with inflammatory rheumatic disease from a rheumatologic outpatient clinic in Norway. Participants had a disease duration of mean 14 years, they were mainly women (n=36) with a mean age of 45 (Standard Deviation =10) years (Table 1). Repeated ANOVA analyses and Paired t-tests showed promising statistically significant changes on a group level for fatigue and depression, not for pain (Table 2). <h3>Conclusions</h3> This pilot project supports the idea of conducting a trial on the effectiveness of a brief cognitive therapy intervention for people with inflammatory rheumatic diseases and fatigue. ANOVA analyses and Paired t-tests showed promising statistically significant changes on a group level for fatigue and depression, but not for pain, whether these changes are clinically meaningful, and if there is a difference, compared to treatment as usual remains to be explored. <h3>Acknowledgements</h3> This project would not have been possible without the support from the national patient organization, through a grant from the Norwegian ExtraFoundation for Health and Rehabilitation. We acknowledge patients who contributed to this project and the staff at the rheumatological outpatient clinic at Diakonhjemmet Hospital. <h3>Disclosure of Interest</h3> None declared
AB0713 Uveitis secondary to spondylarthritis in an ocular inflammation interdisciplinary unit
Authors: D Peiteado, A Pieren, A Schlinker, V Hidalgo, C Millán, E De Miguel, A Balsa
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Objectives</h3> To describe the characteristics of ocular involvement in spondyloarthritis in an ocular inflammation interdisciplinary unit. <h3>Methods</h3> This descriptive study include the patients with uveitis secondary to spondyloarthritis or inflammatory bowel disease (IBD) treated by the rheumatologist from January 2012 to December 2016 in an ocular inflammation multidisciplinary unit. Demographic characteristics, aetiology, ocular involvement pattern, and systemic therapy data were collected and analysed. <h3>Results</h3> From 276 patients evaluated by the rheumatologist, 111 (40.2%) were uveitis secondary to systemic inflammatory diseases. Within this group, the uveitis associated with spondyloarthritis (including also IBD) were the most frequent (68 patients, 61%). Focusing on this group, 57.4% were male with a mean age of 49±15.8 years. 73.5% were HLAB27 positive and 76% had radiologic sacroiliitis. In 24 patients (35.3%) the diagnosis of spondyloarthritis was made after the anamnesis in the uveitis unit. The diagnosis was already known in the other cases. The spondyloarthritis subtypes are described in the table. According to the anatomical distribution, 95.6% were anterior uveitis (AU), followed by the intermediate and posterior ones (1,5% both). 85.3% has unilateral involvement and 10.3% bilateral. Relapsing acute AU was the most frequent pattern (73.5%), followed by non-relapsing acute AU (16.2%) and chronic AU (7.4%). 24 patients (35.3%) required treatment with DMARD to achieve uveitis control. The most commonly used drugs were salazopyrine (7 patients), methotrexate (6 patients), mycophenolate (1), and in another 6 patients anti-TNF treatment was started or the previous dose of the biological was adjusted. The visual acuity (VA) was not perfect (VA≠1 in both eyes) in 35% in the first collected visit. 28% (19 patients) had cataract, and 19% (13) had ocular hypertension. Only 1 patient had bilateral cystoid macular edema. Follow-up data were available for 43 patients and VA was stable in 47%, worsening in 23% and improving in 30% (median follow-up time 23 months, IQR: 6–41) <h3>Conclusions</h3> Our work confirms that in spondyloarthritis the most frequent pattern of ocular involvement is relapsing acute AU. Spondyloarthritis diagnosis was made at the uveitis unit in 35% of patients. More than one-third of patients required systemic therapy for ocular involvement control. Thirty-five percent of the patients had a reduced VA, remaining stable or improving in most, during the follow-up. <h3>Disclosure of Interest</h3> None declared
AB0193 Medical adherence in patients with tightly controlled rheumatoid arthritis
Authors: A Caliskan Uckun, FG Yurdakul, H Bodur
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Medication adherence is very important in the treatment of rheumatoid arthritis (RA). However, medication adherence of the patients with RA was not optimal in many of the studies (1–2). <h3>Objectives</h3> The purpose of this study was to investigate the medication adherence in tightly controlled RA patients and reasons of non-adherence. <h3>Methods</h3> A total of 82 RA patients (65 women and 17 men) who followed regularly in our outpatient clinic were included. Socio-demographic features and medical history were collected. The eight-item Morisky scale (MMAS-8) was used to evaluate adherence to medication. Disease activity score (DAS28), health assessment questionnaire (HAQ), mini mental state examination (MMSE) test and Beck depression inventory (BDI) were evaluated. <h3>Results</h3> According to Morisky scale, 34.1%, 15.9% and 50% of our patients were categorized as low, moderate and high adherence, respectively. The most prevalent noticed barriers for adherence were forgetting medication, inadequate information about using instructions, side effects of medications (Table 1). Socio demographic features, duration of disease, type and number of drugs used per day, the route of drug administration, co-morbid diseases, body mass index, smoking and alcohol consumption were not found to be associated with medication adherence, whereas low MMSE and high BDI score were associated with low medication adherence (p=0.009 and p=0.011, respectively). We found that the disease activity was significantly higher in non-adherent cases (p=0.00) (Table 2). <h3>Conclusions</h3> Our RA patients who were closely followed had 50% high medication adherence. This rate is quite high compared to other studies using MMAS-8. It should be kept in mind that tight control and adequate communication increase medication adherence but different parameters may also be effective. Assessing cognitive disorders and emotional problems of the patient will be beneficial for improving adherence and controlling disease activity. <h3>References</h3> Gadallah MA, Boulos DN, Gebrel A, Dewedar S, Morisky DE. Assessment of rheumatoid arthritis patients9 adherence to treatment. Am J Med Sci. 2015;349:151–6. Ferguson A, Ibrahim FA, Thomas V, Weinman J, Simpson C, Cope AP, Scott DL, Lempp H. Improving medication adherence in rheumatoid arthritis (RA): a pilot study. Psychol Health Med. 2015;20(7):781–9. <h3>Disclosure of Interest</h3> None declared
AB0435 Combination therapy in early stage of rheumatoid arthritis
Authors: SX Matchanov
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> It is known that the early period of rheumatoid arthritis (RA) has a critical role in the development and progression of immune inflammation. Allocation of early RA is due to the need for timely appointment of basic anti-inflammatory drugs to prevent the development of destructive changes in the joints and improve its current forecast. We have proposed a combination of two basic drugs for the treatment of RA, methotrexate (MTX) and leflunomide (LF). While this combination, we proceeded from the basic principles of combination therapy: each of the drugs has an independent clinical effect in early RA, the drugs have different mechanisms of action and different spectrum of side effects. <h3>Objectives</h3> Investigating of clinical efficacy of combination therapy with MT and LF in patients with RA in its early stages <h3>Methods</h3> We observed 80 patients with early RA, 50 patients of them were women and 30 patients were male. The age of patients ranged from 24 up to 42 years old (31,7±7,6), the duration of illness was 6 months. Activity of RA was corresponded to the II degree (DAS 28 &lt;4.7) in 48 patients, III degree (DAS28&gt;5,1) was in 32 patients. 1st group consisted of 40 patients and the 2nd group involved 40 patients. Patients in 1st group received combination therapy with LF in doses 20 mg/day and MT in doses 7.5 mg/week. 2nd group received just MT as a single basic anti-inflammatory drug in doses 7.5 mg/week. In order to improve portability of MT was administered to all patients folic acid in doses 1.2 mg/day, 5 days in a week. The efficiency of the intervention was evaluated after 6 months by reducing of the final value of the indicator of inflammatory activity. <h3>Results</h3> The results of observation of patients for 6 months were showed that, combination therapy with MT and LF provides a quick and pronounced clinical effect in patients in the early stages of RA. Patients of 1st group according to criteria ACR 50- 70% improvement was achieved in 50% of patients, while figure of all indicators of patients in 2nd group was 33.4%. During the treatment was indicated improvement of laboratory parameters of disease activity of RA in both groups, features of activity of 1st group were decreased up to (DAS28 =2,9), signs of 2nd group were (DAS28 =3,6). However, there were 26% of cases of clinical remission of the disease in patients of 1st group than patients of 2nd group. Known side effects of combination therapy with MT and LF in most cases have not been severe, reversible and demanded the abolition of drugs in rare (11.2%) cases. <h3>Conclusions</h3> Combined basic therapy of patients in the early stages of RA with LF and MT has more efficiency than mono therapy. <h3>Disclosure of Interest</h3> None declared
The N6-methyladenosine (m6A)-forming enzyme METTL3 controls myeloid differentiation of normal hematopoietic and leukemia cells
Authors: Ly P Vu, Brian F Pickering, Yuanming Cheng, Sara Zaccara, Diu Nguyen, Gerard Minuesa, Timothy Chou, Arthur Chow, Yogesh Saletore, Matthew MacKay, Jessica Schulman, Christopher Famulare, Minal Patel, Virginia M Klimek, Francine E Garrett-Bakelman, Ari Melnick, Martin Carroll, Christopher E Mason, Samie R Jaffrey, Michael G Kharas
Journal: Nature Medicine (2017)
SAT0661 Finger joint cartilage thickness evaluated by ultrasound in patients with rheumatoid arthritis (RA)
Authors: T Ogura, A Hirata, N Hayashi, H Ito, S Takenaka, Y Fujisawa, K Mizushina, T Katagiri, R Kujime, M Imamura, N Yamashita, H Kameda
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Joint destruction in RA includes both bone and cartilage lesions. By X-ray examination, cartilage destruction is evaluated as a joint space narrowing (JSN). However, joint space narrowing is not a direct evaluation of cartilage. <h3>Objectives</h3> We aimed to examine the finger joint cartilage thickness (CT) by ultrasound (US) imaging and clarify its clinical significance in patients with RA. <h3>Methods</h3> We enrolled 121 RA patients in low disease activity or clinical remission (DAS28-CRP &lt;2.7) in this study. The CT of metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints of 2nd to 5th fingers was bilaterally visualized and measured at the middle portion of MCP and PIP joints from a longitudinal dorsal view, with approximately 90 degrees flexion. In addition, JSN of finger were scored by van der Heijde- modified Sharp method for patients who had a hand X-ray within 2 months. <h3>Results</h3> CT in MCP joints ranged from 0.0 to 1.1 mm (median 0.5 mm), and CT in PIP ranged from 0.0 to 0.6mm (median 0.3mm), respectively. The sum of total CT from 8 fingers ranged from 4.0 to 9.4 mm (median 6.9 mm), and there was a significant difference in total CT, but not in JSN score, between male and female patients (7.4 versus 6.7, p=0.006; and 11 versus 10, p=0.899, respectively). CT was well correlated with JSN (ρ=-0.589, p&lt;0.001; ρ=-0.595, p&lt;0.001 for MCP joints andρ=-0.448, p&lt;0.001 for PIP joints), and both CT and JSN were significantly correlated with disease duration (ρ=-0.282, p=0.002, andρ=0.286, p=0.005, respectively). Notably, CT of MCP, but not of PIP, was inversely correlated with disease duration (ρ=-0.328, p&lt;0.001). Height was correlated with CT (ρ=0.244, p=0.008), but not with JSN (ρ=-0.057, p=0.589). CT and JSN were not correlated with age, functional disability, and seropositivity. <h3>Conclusions</h3> A direct visualization and quantification of finger joint CT, especially MCP joints, by US is valid and useful in RA. <h3>Disclosure of Interest</h3> None declared
Abstract 14481: Oxygen Consumption Flattening During Exercise in Heart Failure: Evidence for a Combined Low Cardiac Output and Inefficient Oxygen Extraction
Authors: Greta Generati, Francesco Bandera, Eleonora Alfonzetti, Marco Guazzi
Journal: Circulation (2016)

Background:  Cardiopulmonary exercise testing (CPET) is useful for an objective functional evaluation of heart failure (HF) patients, allowing to understand the physiological basis of exercise intolerance. A specific pattern of impaired performance and severe exercise limitation is the one showing an early flattening of oxygen uptake (VO2) to maximum.This has been though to be related to a significant cardiac output (CO) impairment but it is undefined whether an increased O2 extraction may compensate for.   Aim:  to study the relationship between CO and O2 extraction in a population of HF reduced ejection fraction (HFrEF) with or without a flattened VO2/WR.   Methods:  116 HFrEF patients (mean age 63±11 y, male 70%, ischemic etiology 69%, mean LVEF 33±9%) underwent a maximal CPET (incremental ramp protocol) combined with exercise-echo. Peripheral extraction (C(a-v)O2) was non-invasively estimated by dividing CPET measured VO2 and echo-derived CO.   Results:  Study population was divided into 2 groups according to VO2/WR relationship: Group A (n=95) linear VO2/WR and B (n=21) non-linear (flattened) VO2/WR. Despite similar rest condition (A vs B CO 3.6±1.2 vs 3.5±1.2 L/min, peak VO2 0.28±0.07 vs 0.27±0.07 L/min, C(a-v)O2 8±3 vs 9±5mL/100mL, p=ns), Group B patients had lower peak VO2 (1.04±0.33 vs 0.73±0.23 L/min, p=0.000) and slightly lower CO, even though non statistically significant (6.7±2.5 vs 5.8±2.1 L/min, p=ns), resulting in markedly reduced peak peripheral extraction (C(a-v)O2 17±5 vs 14±4mL/100mL, p=0.003) compared to Group A.   Conclusions:  In a population of HFrEF, the flattening of VO2/WR relationship phenotype was associated with worse exercise performance and a quite unfavourable hemodynamic combination, i.e. a reduced CO increase and blunted peripheral O2 extraction prospecting the necessity of complex and comprehensive therapeutic interventions integrating central and peripheral cardiovascular targets
AB0042 High expression of s100 calgranulins genes in peripheral blood mononuclear cells of patients with takayasu arteritis
Authors: J Kabeerdoss, R Goel, H Mohan, D Danda
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Takayasu arteritis (TA) is inflammatory disorder that affects aorta and its branches. Toll-like receptors (TLR) 1 to 4 are highly expressed in aorta (1). Activation of TLR4 causes transmural arteritis in human temporal artery–SCID chimera model (2). Ligand responsible for TLR4 activation is not known in TA. <h3>Objectives</h3> Aim of the study is to examine the expression of TLR4 and its endogenous ligands in peripheral blood mononuclear cells (PBMCs) of patient with TA. <h3>Methods</h3> RNA from PBMCs of 24 TA patients and 19 sex and age matched healthy controls were extracted. The mRNA expression of various endogenous TLR4 ligands, TLR4, RAGE, interleukin-6 (IL-6) and IL-8 were quantified in real time PCR using specific primers and SYBR Green qPCR master mix. Serum S100A8/A9 and S100A12 levels were measured using commercial ELISA kits. S100A8/A9 and S100A12 were measured in cell culture supernatant of un-stimulated and lipopolysaccharides (LPS) stimulated PBMCs, cultured for 4 hours. t-test was used to compare between the groups. P&lt;0.05 was considered as statistically significant. <h3>Results</h3> The mRNA of S100A8, S100A9, S100A12 and TLR4 were highly expressed in TA as compared to healthy controls, while RAGE, HSP70 and IL-6 had lower expression in TA. No difference in serum levels of S100A8/A9 and S100A12 was noted between TA and healthy controls. LPS induced high secretion of both S100A8/A9 and S100A12 levels in both TA and healthy controls (Figure-1). However, the stimulatory response in healthy controls [2.88 (1.7–3.53) fold] was significantly higher as compared to TA [1.345 (1–1.82) fold; p&lt;0.05] as measured by delta S100A12 (LPS/unstimulated control). Numerically delta S100A8/A9 was also higher in healthy controls [2.04 (1.7–5.6) fold] as compared to TA [1.38 (1.09–3.6) fold; p=0.129]. <h3>Conclusions</h3> mRNA expression of S100A8, S100A9, S100A12 and TLR4 in PBMCs of TA patients were higher as compared to healthy controls. Despite this, S100A12 secretion was lower in TA as compared to healthy controls upon LPS challenge. <h3>References</h3> Pryshchep O, Ma-Krupa W, Younge BR, et al (2008) Vessel-specific Toll-like receptor profiles in human medium and large arteries. Circulation 118:1276–1284. Deng J, Ma-Krupa W, Gewirtz AT, et al (2009) TLR4 and TLR5 induce distinct types of vasculitis. Circ Res 104:488–495. <h3>Acknowledgements</h3> This study was funded by grants-in-aid from Science and Engineering Research Board (SERB), Department of Science and Technology (DST), Government of India under young investigator scheme to JK (SB/YS/LS-14/2014). <h3>Disclosure of Interest</h3> None declared
FRI0438 Risk factors for uveitis in patients with ankylosing spondylitis: a retrospective cohort study
Authors: EE Lee, MJ Kim, EY Lee, YW Song, EB Lee
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> The uveitis is one of the most common extra-articular manifestation of ankylosing spondylitis (AS), occurring in 20–30% of the patients with AS. But it is not clear which factors are associated with the occurrence of uveitis in patients with AS. <h3>Objectives</h3> To evaluate the risk factors for uveitis in patients with AS. <h3>Methods</h3> A total of 1061 Korean patients who were diagnosed with AS at Seoul National University Hospital between January 2004 and December 2015 were evaluated in this study. Using electronic medical record review, the information on the occurrence of uveitis after AS diagnosis and the other demographic and clinical characteristic were obtained, which included age, gender, disease duration, previous history of uveitis, smoking status, Bath ankylosing spondylitis activity index, HLA-B27 positivity and level of serum inflammatory markers. After dividing the patients into those who experienced uveitis after AS diagnosis (uveitis group) and those who did not (non-uveitis group), the potential risk factors for the occurrence of uveitis were evaluated using univariable and multivariable logistic regression analysis. Receiver operating curve analysis was performed. <h3>Results</h3> Among the 1061 patients, 837 (78.9%) were male and their mean (SD) age was 27.9 (6.2) years. During the observation of 4231 patient-year, uveitis occurred in 142 (13.4%) patients (uveitis group). Patients in the uveitis group had longer disease duration than those in the non-uveitis group (10.0±6.6 vs. 8.2±6.2 years, p=0.003). The proportion of the patients with prior uveitis before diagnosis of AS or HLA-B27 positivity were higher in the uveitis group than those in the non-uveitis group. (58.5% vs. 12.1%, 95.7% vs.83.7%, respectively) There were no significant differences in ESR and CRP between the two groups. In the multivariable analysis, two most significant risk factors for new-onset uveitis was the prior uveitis before the diagnosis of AS (OR=11.18 [95% confidence interval (CI): 7.09–17.63]) and HLA-B27 positivity (OR=9.15 [95% CI: 1.23–68.41]). The area under the curve (AUC) of the final multivariable model was 0.809 (95% CI: 0.77–0.85). Multivariate analysis showed that history of uveitis and the presence of HLA-B27 as the final risk factors for the occurrence of uveitis. <h3>Conclusions</h3> Prior uveitis before the diagnosis of AS and HLA-B27 positivity were associated with the occurrence of uveitis. These results can be useful to predict occurrence of uveitis in patients with AS. <h3>Disclosure of Interest</h3> None declared