bluuebunny/crossref_metadata_2025_split huggingface dataset:
EP21 An observational study of the predictors of osteoporosis in men
Authors: Kyrtata Natalia , Davies Kristen , Nune Arvind , Bukhari Marwan 
Published: April 2020

Abstract

Background
Osteoporosis is under-recognised and under-treated in men. Previous studies and stratification tools have been limited in their generalisability and while predictors of poor bone density in men have been characterised, evidence has been contradictory. The purpose of this study is to investigate these predictors in the lumbar spine and femoral neck in men.

Methods
Data were collected from 3,901 men referred for DEXA scanning to the Royal Lancaster Infirmary, between 2004 and 2010. BMD was measured in the lumbar spine and femoral neck. Simple and multiple regression models were fitted to each measurement site, using each of the known predictors for poor bone health. The Variance Inflation Factor was used to quantify the severity of multicollinearity and the Akaike Information Criterion was employed to select co-variates.

Results
The following predictors had a significant effect in both measurement sites: age; height; weight; Body Mass Index (BMI); X-ray evidence of osteopenia; and previous fracture(s). Body fat percentage had a significant effect at the lumbar spine only, and tobacco use had a significant effect at the femoral neck only. The adjusted R squared values for the models ranged from 0.16 for the lumbar spine model, to 0.28 for the femoral neck model.

Conclusion
This study demonstrated that further work is needed in assessing the predictors of OP in men. This would open up an interesting observation in clinical practice and provide an opportunity for risk prediction and primary prevention of OP in men, reducing fracture risk. Future studies should include randomised samples and propensity score matching.

Disclosures
N. Kyrtata None. K. Davies None. A. Nune None. M. Bukhari None.
EP23 Subcutaneous methotrexate from the get-go: better adherence and tolerability
Authors: Bevington Catherine , Achilleos Katerina , Smith Jessica , Smith Victoria 
Published: April 2020

Abstract

Background
Several studies have shown subcutaneous methotrexate (s/c MTX) to be superior to oral for treatment of rheumatoid arthritis. However s/c MTX is rarely started first line.

Methods
We audited the first 67 patients started on s/c MTX at diagnosis and compared to a previous cohort of treat-to-target patients started on oral MTX.

Results
There was a significant difference in adherence: for every 1 patient staying on oral, 1.5 patients stayed on s/c MTX. There was no difference in final numbers in remission, escalation to biologics, or time to remission. Nearly half the patients on oral MTX had switched to s/c at 1 year, either for side effects or inefficacy.

Conclusion
Adherence to s/c MTX was better than adherence to oral MTX in our study. The large number of switches from oral to s/c suggests that adherence is improved due to improved tolerability and reduced side effects of s/c MTX.

Disclosures
C. Bevington None. K. Achilleos None. J. Smith Grants/research support; JS received £500 from Medac to carry out the audit. V. Smith: None.
EP28 Adenosine deaminase-genetic polymorphism and baseline serum level as a biomarker of treatment response to methotrexate in rheumatoid arthritis
Authors: Nair Harikrishnan Gangadharan , Singh Ankita , Majumder Sanjukta , Aggarwal Amita 
Published: April 2020

Abstract

Background
Despite methotrexate (MTX) being the first line therapy for RA,30% of patients do not respond to MTX. Methotrexate acts by increasing adenosine levels which lead to anti-inflammatory effects. Adenosine deaminase (ADA) enzyme converts adenosine to inosine thus reduces levels of adenosine. Thus, ADA levels and single nucleotide polymorphism (SNP) in ADA gene may affect the treatment effect of MTX. Our objective was to study if genetic polymorphism in ADA gene and baseline serum ADA levels in patients with RA is associated with methotrexate response.

Methods
207 DMARD naïve active RA (DAS28 ESR ≥3.2) patients satisfying EULAR/ACR 2010 criteria were enrolled. Genotyping was done in all patients (n = 207) by TaqMan 5' nuclease assay. In a subset of patients(n = 59) blood sample was collected at baseline and 2 months for ADA estimation by ELISA. Ethical approval and written informed consent was taken. Oral MTX was initiated at dose of 15mg/week, escalated 5mg every month till the patients had DAS28 &lt; 2.6 or a maximum dose of 25 mg/week was reached. At 4 months based on EULAR response patients were classified as responders or non-responders. Using a Chi-squared test, SNPs were associated with response to methotrexate therapy. Baseline clinical parameters and serum ADA levels were correlated with EULAR response.

Results
Among 207 patients (177females) mean age was 41.49± 12.14 years and median disease duration 24 (40) months.172 patients (83.1%) were responders and 35 (16.9%) non-responders. 197 (95.16%) patients were seropositive (RF and/or ACCP+). With regard to SNP in ADA gene,47.8% were AA,42.5% AG and 9.7% were GG genotype. Mean DAS 28 CRP was 4.76 ± 1.05 and median DAS 28 ESR was 6.00 (1.38). Mean serum baseline ADA was 10.82 ±5.33 pg/dl. Except DAS28ESR (p = 0.02), other baseline parameters like age, disease duration, ESR, CRP, DAS 28 CRP were similar between responders and non-responders. SNPs in ADA gene were not associated with EULAR response (p = 0.475). Baseline ADA levels (10.52 ± 5.37 vs 12.28 ± 5.14; p = 0.34) 2 month ADA levels (p = 0.34) and change in ADA level from baseline at 2 months, i.e. delta ADA (p = 0.55) did not show any association with MTX response. Mean ADA level was similar between the 3 genotypes of ADA(p = 0.736) Comparison of parameters between methotrexate responders and non-responders

Conclusion
ADA gene polymorphism and serum ADA levels do not affect response to methotrexate.

Disclosures
H. Gangadharan Nair: Grants/research support; Indian Rheumatology Association Research grant. A. Singh: None. S. Majumder None. A. Aggarwal None.
EP36 Vitamin D and interferon signature gene expression in systemic lupus erythematosus: a cross-sectional cohort study
Authors: Magro Rosalie , Saliba Christian , Camilleri Liberato , Scerri Christian , Borg Andrew A 
Published: April 2020

Abstract

Background
Vitamin D deficiency is more prevalent in patients with systemic lupus eythematosus (SLE) as a result of sun avoidance. The potential negative impact of vitamin D deficiency on the disease activity of SLE has been shown in a number of studies. The expression of the interferon signature genes in SLE correlates positively with disease activity, and these genes are thought to mediate the clinical manifestations of the disease. The aim of this study was to establish whether a relationship exists between serum 25-hydroxyvitamin D level and the interferon signature gene expression in whole blood of SLE patients.

Methods
Informed consent was obtained from 92 SLE patients who were over the age of 18 and who fulfilled the SLICC classification criteria for SLE. The patients were interviewed and blood tests including full blood count, renal profile, calcium, 25-hydroxyvitamin D, complement 3 (C3), complement 4 (C4) and anti-double standed DNA (anti-dsDNA) titre were carried out. SLE disease activity was measured by SLE disease activity index-2K (SLEDAI-2K). RNA extraction was performed from whole blood. QuantiGene Plex technology was used to measure the expression of 12 interferon signature genes in the extracted RNA. The study was approved by the University Research Ethics Committee.

Results
92.4% of the cohort studied were female. 58.7% were receiving vitamin D3 supplementation at a mean dose of 1031IU daily. 27.2% had vitamin D insufficiency (25-hydroxyvitamin D 21-29ng/ml) and 15.2% were vitamin D deficient (25-hydroxyvitamin D &lt; 20ng/ml). Mean serum 25-hydroxyvitamin D was 30.75ng/ml (standard deviation 9.53 ng/ml). Median SLEDAI-2K was 4 (range 0-12). Serum 25-hydroxyvitamin D had a significant negative correlation with body mass index (BMI) (R=-0.258, p = 0.006) but there was no significant negative correlation with SLEDAI-2K or with the expression of the interferon signature genes. The expression of most interferon signatures genes measured (IFI35, OAS1, MX1, IFITM1, STAT2, IFIT3, IFIT1, STAT1, SOCS1) had a significant positive correlation with SLEDAI-2K.

Conclusion
This study did not show a significant relationship between serum vitamin D level and disease activity. In keeping with this, there was no significant negative correlation between serum 25-hydroxyvitamin D and interferon signature gene expression. Further prospective studies and randomised controlled trials are required to study this relationship in greater depth.

Disclosures
R. Magro None. C. Saliba None. L. Camilleri None. C. Scerri None. A.A. Borg None.
EP40 Real world efficacy of secukinumab: a single centre experience
Authors: Blake Tim , Gullick Nicola J 
Published: April 2020

Abstract

Background
Secukinumab was approved by NICE for patients with active ankylosing spondylitis and psoriatic arthritis in 2017. Clinical trial data suggests secukinumab is a useful treatment option in both conditions, but often real world experience differs greatly from clinical trial results. In addition, patients with more refractory disease are often excluded from clinical trials.

Methods
Patients starting secukinumab at UHCW were identified from the Blueteq funding database. Medical notes were reviewed retrospectively to assess response rates using BASDAI responses in Ankylosing spondylitis and PsARC responses in PsA. Patients who had previously had inadequate response to TNF inhibitors (PsA only) and severe psoriasis received 300mg secukinumab monthly; the remainder were prescribed 150mg monthly.

Results
113 patients commenced secukinumab between June 2017 and April 2019 and had outcome data recorded. 59 patients (52%) had received previous biologic agents prior to secukinumab exposure. Patients with ankylosing spondylitis had high BASDAI (6.91.4) and spinal pain (7.71.4). 38 patients had an initial response to treatment. Secukinumab was effective in 39 patients (63%), and 37 (62%) continued treatment. In psoriatic arthritis, despite high levels of activity at baseline (mean tender joint count 10 8; swollen joint count 63, and 65% prior biologic exposure, high rates of response were seen. The majority of patients have continued treatment. Secukinumab was well tolerated in both patient groups with low rates of discontinuation due to adverse events (11 patients, 9%). Adverse events included recurrent infection (6), rash (1), mouth ulcers (1), vertigo (1), new onset cancer (1) and new onset Crohn’s (1) although rates were low overall. Patients with pre-existing uveitis did not develop exacerbations but low numbers of patients with prior uveitis were treated.

Conclusion
Secukinumab demonstrates high levels of efficacy even in a cohort of patients with longstanding PSA and AS with high rates of inadequate responses to other biologics. Secukinumab is well tolerated with low rates of discontinuation due to adverse events.
Disclosures: T. Blake: None. N.J. Gullick: Honoraria; NG has received Honoraria from Abbvie, Eli Lilly, Novartis, UCB. Grants/research support; NG has received funding for research from Abbvie and Novartis.
O18 National variation and factors associated with long-term opioid use for non-cancer pain in the first year of use
Authors: Jani Meghna , Birlie-Yimer Belay , Sheppard Therese , Lunt Mark , Dixon William G 
Published: April 2020

Abstract

Background
Physician prescribing behaviour has been described as a key driver of rising opioid prescriptions and long-term opioid use. However, the effect of prescribers requires interpretation within context. No studies have investigated the extent to which regions, practices, prescribers, vary in opioid prescribing by considering this hierarchy together, whilst accounting for case-mix. Objectives: (i)quantify and identify risk factors for the transition from new-users to long-term opioid users (ii) quantify variation of long-term use attributed to region, practice, prescriber, accounting for patient mix and chance variation.

Methods
We conducted a retrospective observational study between 2006-2017 using Clinical Practice Research Datalink. New users of opioids, ≥18 years, without cancer were identified. Long-term opioid use was defined as ≥ 3 opioid prescriptions within a 90-day period from index date, or ≥ 1 opioid prescription lasting at least 90-days in the first year. A multi-level random-effects logistic regression model was used to examine the association of patient characteristics with the odds of becoming a long-term opioid-user. To examine variation in opioid use among prescribers, GP-practices and region after adjusting for case-mix, we used a nested random-effect structure. A ‘high-risk’ region, prescriber or practice was defined as those where the entire adjusted 95% CI lay above population average.

Results
1,968,742 new opioid users were included; 14.6% transitioned to long-term use. In the fully-adjusted model, factors associated with higher-odds of long-term use included high morphine-milligram equivalents (MME)/day at first prescription, older-age, deprivation, fibromyalgia, rheumatological conditions and prior surgery (Table 1). After adjustment for case-mix, the North-West, Yorkshire and South-West were found to be high-risk regions for long-term use. 103 practices (25.6%) and 540 prescribers (3.5%) were associated with a significantly higher risk of long-term use. The odds of becoming a long-term user for patients belonging to these prescribers reached up to &gt; 3.5 times than the population average.

Conclusion
Prescribing factors, age, deprivation and conditions including fibromyalgia and rheumatological conditions were associated with higher odds of long-term opioid use. In the first UK study evaluating long-term opioid prescribing with patient-level characteristics adjustment, variation in regions, especially practices and prescribers were observed. Our findings support greater calls for action to reduce practice/prescriber variation by promoting safe practice in opioid-prescribing.

Disclosures
M. Jani: None. B. Birlie-Yimer: None. T. Sheppard: None. M. Lunt: None. W.G. Dixon: None.
O29 Methotrexate response clusters in JIA
Authors: Shoop-Worrall Stephanie J. W , Hyrich Kimme L , Wedderburn Lucy R , Thomson Wendy , Geifman Nophar ,   CLUSTER, BSPAR-ETN, BCRD
Published: April 2020

Abstract

Background
Treatment response in juvenile idiopathic arthritis (JIA) is currently viewed as a binary outcome of response versus non-response. In a heterogenous disease such as JIA, it is likely that different, identifiable clusters of children and young people (CYP) may display varying patterns of the different features of the disease. Identifying these response clusters is an important step toward stratified medicine in JIA. The aim of the study was to explore trajectories of juvenile arthritis disease activity score (JADAS) components following methotrexate (MTX) initiation for JIA.

Methods
MTX-naïve CYP with JIA were selected if enrolled prior to January 2018 in either the UK BSPAR Etanercept Register or the Biologics for Children with Rheumatic Diseases Study at point of starting MTX. JADAS components (active joint count, physician’s global assessment (0-10cm), parental global evaluation (0-10cm) and standardised ESR (0-10) were calculated based on data collected in the year following MTX initiation. Multivariate group-based trajectory models were used to explore MTX response clusters across the different JADAS components, using censored-normal (global scores, ESR) and zero-inflated Poisson (active joint count) models. Optimal models were selected based on a combination of model fit (BIC), parsimony and clinical plausibility.

Results
Of 611 CYP selected, the majority were female (69%) and of white ethnicity (85%), with RF-negative JIA the most common disease category (33%). The optimal model identified multiple patterns of disease activity following initiation of MTX, which have greater complexity than simple ‘response’ versus ‘non-response’ clusters. Differences between clusters included initial intensity of disease features and speeds of improvement over time. In addition, the components of the JADAS did not always follow similar patterns over time, even within the same outcome cluster.

Conclusion
This study has identified that within CYP initiating MTX, different patterns of disease activity are apparent, suggesting that a simple responder/non-responder analysis at a set point may be inadequate. Understanding both clinical factors associated with, and biological mechanisms underpinning, these clusters would aid stratified medicine in JIA.

Disclosures
S.J.W. Shoop-Worrall None. K.L. Hyrich None. L.R. Wedderburn None. W. Thomson None. N. Geifman None.
O30 Long non-coding RNA HOTAIR induces beta catenin expression in systemic sclerosis through EZH2 dependent repression of Axin-2
Authors: Wasson Christopher W , Abignano Giuseppina , Ross Rebecca , Galdo Francesco Del 
Published: April 2020

Abstract

Background
Fibroblasts explanted from affected tissues in systemic sclerosis (SSc) maintain their pro-fibrotic phenotype in vitro. This includes increased secretion of collagens and other extracellular matrix proteins and increased proportion of α-Smooth Muscle Actin (α-SMA) positive cells (myofibroblasts). It has been previously shown that among their profibrotic features, myofibroblasts display activation of WNT signalling, which is linked to a decreased basal expression of AXIN2. Here we aimed to determine whether specific long non-coding RNA (lncRNAs) expressed in myofibroblasts could drive the epigenetically stable decreased expression of Axin 2 in vitro.

Methods
Full thickness skin biopsies were surgically obtained from the forearms of twelve adult patients with SSc of recent onset. Fibroblasts were isolated and cultured in monolayers and protein and RNA extracted from the fibroblast cultures. Laser capture was performed to isolate cells expressing or not α-SMA as a marker of myofibroblast differentiation. LncRNA HOTAIR was overexpressed in healthy dermal fibroblasts by lentiviral induction. EZH2 was blocked in cultured fibroblasts with the specific inhibitor GSK126.

Results
HOTAIR expression was increased in SSc patients’ skin (100 fold) and in SSc explanted fibroblasts (5 fold; p &lt; 0.001 for both). Further, laser captured α-SMA expressing fibroblasts expressed in average 2.5 fold higher HOTAIR RNA levels compared to α -SMA negative cells from the same donors (P &lt; 0.05). In vitro, lentiviral induced stable overexpression of HOTAIR in healthy dermal fibroblasts led to their profibrotic activation, including significantly increased expression of Col1A1 and α-SMA both at mRNA and protein levels (2.8 and 1.8 fold respectively, p &lt; 0.05). We further showed that HOTAIR-induced profibrotic activation was due to EZH2 dependent spread of H3k27me3 methylation marker, as demonstrated by complete inhibition by treatment with GSK126. HOTAIR driven EZH2 histone methylation suppressed the expression of Axin 2 in SSc fibroblasts. The reduced Axin 2 levels led to stabilisation of beta catenin and WNT signalling pathway activation.

Conclusion
Here we show that the epigenetically stable activation of SSc dermal fibroblasts is due to HOTAIR. We also identified a major downstream target of HOTAIR is Axin-2. The results of these studies identify a new venue to modulate fibroblasts biology which could inform clinical research to resolve chronic fibrosis and re-establish tissue homeostasis in SSc.

Disclosures
C.W. Wasson None. G. Abignano None. R. Ross None. F. Del Galdo Consultancies; AstraZeneca, GSK, Boehringer-Ingelheim, Actelion, Capella Biosciences, Chemomab.
O38 The relationship between obesity and outcomes in patients with polymyalgia rheumatica
Authors: Scott Ian C , Bajpai Ram , Hider Samantha L , Helliwell Toby , Muller Sara , Mallen Christian D 
Published: April 2020

Abstract

Background
Obesity predisposes to a pro-inflammatory state. Studies have reported worse clinical outcomes in patients with inflammatory arthritis who are obese. The relationship between obesity and outcomes in patients with polymyalgia rheumatica (PMR), another common inflammatory rheumatic condition, has not been assessed. We examined this in a cohort study of primary care-recruited patients with PMR.

Methods
The PMR Cohort Study is an inception cohort of patients with incident PMR, recruited from 382 general practices. Self-completed questionnaires at 0, 12, and 24-months captured: (a) PMR-related pain (0-10 numeric rating scale [NRS]); (b) PMR-related stiffness (0-10 NRS); (c) anxiety (GAD7); (d) depression (PHQ8); (e) fatigue (FACIT-Fatigue); (f) function (mHAQ); (g) quality of life (EQ-5D-3L). Height was self-reported at baseline, and weight at baseline, 12 and 24 months. Patients were categorised as underweight (BMI&lt;18.5 kg/m2); normal weight (18.50-24.99 kg/m2); overweight (25-29.99 kg/m2); or obese (≥30 kg/m2). Piecewise, multivariable, multilevel, linear mixed-effects regression models examined relationships between BMI categories and outcomes over time, using restricted cubic spline functions. Adjustments were made for age, sex, prednisolone-use, smoking, and alcohol. Due to few underweight patients (three at 0 months; one at 12/24 months), underweight and normal weight patients were combined, as a single reference group.

Results
652 patients were included (62% female). At baseline, mean age was 72 years, median BMI 26.6 (IQR 24.0-30.2), 34% were normal/under-weight, 40% overweight, and 26% obese. Compared to normal/underweight patients, obese patients had the following significantly poorer outcomes (P&lt;0.05): higher pain scores at 12-months; higher stiffness scores at 12 and 24 months; higher depression levels at 12 and 24 months; worse fatigue at 0, 12 and 24 months; worse function at 12 and 24 months; worse quality of life at 0, and 12 months. BMI changed little over 24 months (25.7% and 25.9% obese at 0 and 24-months, respectively).

Conclusion
Obesity is associated with poorer outcomes in patients with PMR. Consideration should be given to providing weight management support to patients with PMR and obesity. Further research should examine the impacts of weight-based steroid dosing on outcomes.

Disclosures
I.C. Scott None. R. Bajpai None. S.L. Hider None. T. Helliwell None. S. Muller None. C.D. Mallen None.