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Introduction Limited data are available on the influence of multimorbidity on the outcomes of total hip replacement for patients with hip osteoarthritis, including the rate of complications and degree of functional benefit. The aim of this study was to investigate the influence of multimorbidity on the outcomes of total hip replacement in the UK. Method A cohort study was performed, with cohort comprised of all patients over 65 years with a diagnosis of hip osteoarthritis recorded in Clinical Practice Research Datalink and receipt of primary total hip replacement recorded in Hospital Episode Statistics Admitted Patient Care. Severity of multimorbidity burden was measured using four different scores (Charlson Comorbidity Index, Electronic Frailty Index, count of drugs prescribed, count of primary care interactions). The outcomes were (i) the risks of total hip replacement, assessed by serious post-operative complications within 90 days (analysed with logistic regression), and (ii) the benefits of surgery, assessed by post-operative Oxford Hip Score (OHS) and EQ-5D quality of life score (analysed with linear regression). Results 6,682 patients were included. The rate of complications was 3.2%. Patients with severe multimorbidity burden were at 1.5 to 2.5 times increased risk of complications than patients without multimorbidity. There was no clinically meaningful difference in the benefits of surgery between patients with and without multimorbidity, irrespective of the method of scoring multimorbidity. Conclusions Even for patients with severe multimorbidity burden, the potential benefits of total hip replacement for osteoarthritis remain substantial, while the increase in risk is relatively small.

Introduction Limited data are available on the influence of multimorbidity on the outcomes of total hip replacement for patients with hip osteoarthritis. Thus, patients with multimorbidity and their clinicians across the UK are making decisions on whether or not to proceed with total hip replacement without clear information available on the potential risks and benefits. It is not known how such patients are currently managed. The aim of this study was to investigate the influence of multimorbidity on the likelihood of receiving total hip replacement in patients with hip osteoarthritis in the UK. Method A cohort study was performed, with cohort comprised of all patients over 65 years with a diagnosis of hip osteoarthritis recorded in Clinical Practice Research Datalink. Severity of multimorbidity burden was measured using four different scores (Charlson Comorbidity Index, Electronic Frailty Index, count of drugs prescribed, count of primary care interactions). The outcome was total hip replacement, evaluated using Kaplan-Meier survival and competing-risk analyses. Results 28,025 patients were included. 10,948 patients underwent total hip replacement. Increased multimorbidity burden was associated with decreased likelihood of undergoing surgery, irrespective of the method of scoring multimorbidity. Electronic Frailty Index had the largest difference between categories. Adjusted hazard ratio (‘severe multimorbidity versus ‘fit’) was 0.34 (95% CI 0.22, 0.51). Conclusions Patients with hip osteoarthritis and concurrent multimorbidity were up to two thirds less likely to undergo total hip replacement. Whether this difference in healthcare management is appropriate depends on to what extent multimorbidity influences the outcomes of total hip replacement.

The European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) CKD-MBD working group, in collaboration with the Committee of Scientific Advisors of the International Osteoporosis Foundation, published a position paper for the diagnosis and management of osteoporosis in patients with CKD stages 4-5D (eGFR < 30 ml/min 1.73 m2). The present article reports and summarizes the main recommendations included in this 2021 document. The following areas are reviewed: diagnosis of osteoporosis; risk factors for fragility fractures; fracture risk assessment; intervention thresholds for pharmacological intervention; general and pharmacological management of osteoporosis; monitoring of treatment, and systems of care, all in patients with CKD stages 4-5D. Guidance is provided for clinicians caring for CKD stages 4-5D patients with osteoporosis, allowing for a pragmatic individualized diagnostic and therapeutic approach as an alternative to current variations in care and treatment nihilism.

Background Osteoarthritis (OA) is a chronic joint disease, with increasing global burden of disability and healthcare utilisation. Recent meta-analyses have shown a range of effects of OA on mortality, reflecting different OA definitions and study methods. We seek to overcome limitations introduced when using aggregate results by gathering individual participant-level data (IPD) from international observational studies and standardising methods to determine the association of knee OA with mortality in the general population. Methods Seven community-based cohorts were identified containing knee OA-related pain, radiographs, and time-to-mortality, six of which were available for analysis. A two-stage IPD meta-analysis framework was applied: (1) Cox proportional hazard models assessed time-to-mortality of participants with radiographic OA (ROA), OA-related pain (POA), and a combination of pain and ROA (PROA) against pain and ROA-free participants; (2) hazard ratios (HR) were then pooled using the Hartung–Knapp modification for random-effects meta-analysis. Findings 10,723 participants in six cohorts from four countries were included in the analyses. Multivariable models (adjusting for age, sex, race, BMI, smoking, alcohol consumption, cardiovascular disease, and diabetes) showed a pooled HR, compared to pain and ROA-free participants, of 1.03 (0.83, 1.28) for ROA, 1.35 (1.12, 1.63) for POA, and 1.37 (1.22, 1.54) for PROA. Discussion Participants with POA or PROA had a 35–37% increased association with reduced time-to-mortality, independent of confounders. ROA showed no association with mortality, suggesting that OA-related knee pain may be driving the association with time-to-mortality. Funding Versus Arthritis Centre for Sport, Exercise and Osteoarthritis and Osteoarthritis Research Society International.

Summary This study demonstrates a substantial and persistent anti-osteoporosis treatment gap in men and women ≥50 years old who sustained major osteoporotic fracture(s) between 2005 and 2014 in Denmark. This was not substantially reduced by including hospital-administered anti-osteoporosis treatments. Strengthened post-fracture organization of care and secondary fracture prevention is highly needed. Introduction The purpose of this study was to evaluate the Danish anti-osteoporosis treatment gap from 2005 to 2014 in patients sustaining a major osteoporotic fracture (MOF), and to assess the impact of including hospital-administered anti-osteoporosis medications (AOM) on the treatment gap among these patients. Methods In this retrospective, registry-based study, we included men and women aged 50 years or older and living in Denmark, who sustained at least one MOF between 2005 and 2014. We applied a repeated cross-sectional design to generate cohorts of patients sustaining a first MOF, hip, vertebral, humerus, or forearm fracture, respectively, within each calendar year. We evaluated the treatment gap as the proportion of patients within each cohort not receiving treatment with AOM within 1 year of the fracture. Hospital-administered AOM was identified by SKS code. Results The treatment gap among MOF patients decreased from 85% in 2005 to 79% in 2014. The gap was smaller among hip and vertebral fracture patients as compared to humerus and forearm fracture patients, and it was smaller in women than in men. The use of hospital-administered AOM was relatively uncommon, with a maximum of 0.9% of MOF patients initiating hospital-administered AOM (in 2012). We observed substantial variations in this proportion between fracture types and gender. Hospital-administered AOM was most commonly used among vertebral fracture patients. Conclusion A significant treatment gap among patients sustaining a major osteoporotic fracture was present throughout our analysis, and including hospital-administered AOM did not significantly improve the treatment gap assessment. Improved secondary fracture prevention is urgently needed.

BackgroundHydroxychloroquine has recently received Emergency Use Authorization by the FDA and is currently prescribed in combination with azithromycin for COVID-19 pneumonia. We studied the safety of hydroxychloroquine, alone and in combination with azithromycin.MethodsNew user cohort studies were conducted including 16 severe adverse events (SAEs). Rheumatoid arthritis patients aged 18+ and initiating hydroxychloroquine were compared to those initiating sulfasalazine and followed up over 30 days. Self-controlled case series (SCCS) were conducted to further establish safety in wider populations. Separately, SAEs associated with hydroxychloroquine- azithromycin (compared to hydroxychloroquine-amoxicillin) were studied. Data comprised 14 sources of claims data or electronic medical records from Germany, Japan, Netherlands, Spain, UK, and USA. Propensity score stratification and calibration using negative control outcomes were used to address confounding. Cox models were fitted to estimate calibrated hazard ratios (CalHRs) according to drug use. Estimates were pooled where I2ResultsOverall, 956,374 and 310,350 users of hydroxychloroquine and sulfasalazine, and 323,122 and 351,956 users of hydroxychloroquine-azithromycin and hydroxychloroquine-amoxicillin were included. No excess risk of SAEs was identified when 30-day hydroxychloroquine and sulfasalazine use were compared. SCCS confirmed these findings. However, when azithromycin was added to hydroxychloroquine, we observed an increased risk of 30-day cardiovascular mortality (CalHR2.19 [1.22- 3.94]), chest pain/angina (CalHR 1.15 [95% CI 1.05-1.26]), and heart failure (CalHR 1.22 [95% CI 1.02- 1.45])ConclusionsShort-term hydroxychloroquine treatment is safe, but addition of azithromycin may induce heart failure and cardiovascular mortality, potentially due to synergistic effects on QT length. We call for caution if such combination is to be used in the management of Covid-19.Trial registration numberRegistered with EU PAS; Reference number EUPAS34497 (http://www.encepp.eu/encepp/viewResource.htm?id=34498). The full study protocol and analysis source code can be found at https://github.com/ohdsi-studies/Covid19EstimationHydroxychloroquine.Funding sourcesThis research received partial support from the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC) and Senior Research Fellowship (DPA), US National Institutes of Health, Janssen Research & Development, IQVIA, and by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea [grant number: HI16C0992]. Personal funding included Versus Arthritis [21605] (JL), MRC-DTP [MR/K501256/1] (JL), MRC and FAME (APU). The European Health Data & Evidence Network has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No 806968. The JU receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA. No funders had a direct role in this study. The views and opinions expressed are those of the authors and do not necessarily reflect those of the Clinician Scientist Award programme, NIHR, NHS or the Department of Health, England.

Background:Few previous studies have investigated the incidence rate (IR) and point prevalence (PP) of seropositive and seronegative rheumatoid arthritis (RA), and further, the estimates remain unknown in the Danish population.Objectives:To investigate the IR and PP of seropositive and seronegative RA in the adult Danish population from 1998 to 2018 using four register-based case definitions of RA.Methods:Nationwide register-based cohort study. Using the Danish administrative registers, patients with RA between 1998 and end of 2018 were identified. ICD-10 codes for RA were identified in the Danish National Patient Registry and information on DMARD prescriptions were obtained through the Danish National Prescription Registry using ATC codes. The used case definitions were1: Criteria A, first time M05/M06 RA diagnosis and redemption of a DMARD in the following year; Criteria B, two RA diagnoses within 90 days of each other, originating from department of rheumatology or general internal medicine, where the latest registered M05/M06 diagnosis defined the serologic status; Criteria C, a M05/M06 diagnosis recorded at any time preceded or followed by redemption of a DMARD prescription within one year, where the M05/M06 diagnosis recorded determined the serologic status; Criteria D, as Criteria A, but with the additional requirements that cases had no registration for other selected inflammatory diseases.In calculation of IRs the total Danish population from 1998 to 2018 was used as reference population for standardisation. The PP was calculated for years 2000, 2009, 2011 and 2018.Results:From 1998 to 2018 the overall IR was 18.0 (95%CI 17.7 to 18.3) per 100,000 person years (PY) for seropositive RA and 16.7 (95%CI 16.4 to 16.9) per 100,000 PY for seronegative RA using Criteria A. A higher IR for seropositive RA than for seronegative RA was found regardless of the case criteria used. Figure 1 shows the temporal IRs of seropositive and seronegative RA.Regardless of case criteria used, the PP increased from 2000 to 2018 for both seropositive and seronegative RA, and the estimates were higher for seropositive RA than for seronegative RA (Table 1).Table 1.Point prevalence of rheumatoid arthritis in Denmark in year 2000, 2009, 2011 and 2018 using four different case definitions2000200920112018SeropositiveSeronegativeSeropositiveSeronegativeSeropositiveSeronegativeSeropositiveSeronegativeCriteria AN3029274174747127871281211243711662Population3964040416629842028914269677PP, % (95%CI)0.08 (0.08 to 0.08)0.07 (0.07 to 0.07)0.18 (0.18 to 0.19)0.17 (0.17 to 0.18)0.21 (0.20 to 0.21)0.19 (0.19 to 0.20)0.27 (0.27 to 0.28)0.26 (0.25 to 0.26)Criteria BN7507489311565903312710100111633413340PP, % (95%CI)0.20 (0.19 to 0.20)0.13 (0.12 to 0.13)0.28 (0.28 to 0.29)0.22 (0.21 to 0.22)0.30 (0.30 to 0.31)0.24 (0.23 to 0.24)0.36 (0.35 to 0.36)0.29 (0.29 to 0.30)Criteria CN6701457011174912512417101491588113712PP, % (95%CI)0.18 (0.17 to 0.18)0.12 (0.12 to 0.12)0.27 (0.27 to 0.28)0.22 (0.22 to 0.23)0.29 (0.29 to 0.30)0.24 (0.24 to 0.25)0.35 (0.34 to 0.35)0.30 (0.30 to 0.31)Criteria DN272423906612598476956759108309452PP, % (95%CI)0.07 (0.07 to 0.07)0.06 (0.06 to 0.07)0.16 (0.16 to 0.16)0.15 (0.14 to 0.15)0.18 (0.18 to 0.19)0.16 (0.16 to 0.17)0.24 (0.23 to 0.24)0.21 (0.20 to 0.21)PP = Point prevalenceConclusion:In Denmark, the IR and PP estimates were higher for seropositive compared to seronegative RA during the study period. However, when applying stricter case criteria for RA (Criteria A and D) the differences in IR and PP estimates were smaller, than when using less strict criteria (Criteria B and C). The findings of such small differences between seropositive and seronegative IRs warrant further investigation.References:[1]Soussi BG et al. Incidence and prevalence of rheumatoid arthritis in Denmark: a nationwide population based study investigating the effect of four different case definitions [abstract]. Ann Rheum Dis. 2020;79(supplement 1):46Acknowledgements:The authors will like to thank The Danish Rheumatism Association for supporting this work.Disclosure of Interests:Bolette Gylden Soussi: None declared, René Lindholm Cordtz: None declared, Salome Kristensen: None declared, Christian Sørensen Bork: None declared, Jeppe Christensen: None declared, Erik Berg Schmidt: None declared, Daniel Prieto-Alhambra Grant/research support from: Grants from AMGEN, UCB Biopharma and Les Laboratoires Servier; and Janssen, on behalf of IMI-funded EHDEN and EMIF consortiums, and Synapse Management Partners have supported training programmes organised by DPA’s department and open for external participants, Lene Dreyer Grant/research support from: Grants from BMS, Galderma and Eli Lilly.

Resumen: Objetivo: Determinar si existen diferencias en la prevalencia del uso de fármacos para la osteoporosis entre pacientes diabéticos tipo 2 (DM2) y no diabéticos. Material y método: Estudio de cohortes retrospectivas con datos del Sistema de Información para el Desarrollo de la Investigación en Atención Primaria (SIDIAP), que contiene información clínica anonimizada de más de 5 millones de pacientes de Cataluña. Se seleccionaron todos los pacientes de ≥50 años de edad con diagnóstico de DM2, que fueron apareados con dos sujetos sin diabetes. Se recogió información sobre variables descriptivas, fracturas prevalentes y el uso de fármacos para la osteoporosis agrupados en bifosfonatos (BF), suplementos calcio y vitamina D (CaD), y cualquier fármaco para la osteoporosis (FPO). Mediante regresión logística se calculó la asociación entre la presencia de DM2 y el uso de FPO, ajustando por variables confusoras. Resultados: Se identificaron 166.106 pacientes con DM2 y 332.212 no diabéticos. Los DM2 tenían mayor prevalencia de fractura que los no diabéticos (1,3% vs. 0,3%). El uso de BF en los pacientes con DM2 era del 6,6%, frente al 9,3% en los no diabéticos (p

Background:Cytopenia is a known side-effect of conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) in rheumatoid arthritis (RA). There is a lack of data on the comparative risk of cytopenia with different csDMARDs.Objectives:To assess the comparative risk of leukopenia and pancytopenia for the most frequently used first-line csDMARDs: methotrexate (MTX), hydroxychloroquine (HCQ), sulphasalazine (SSZ), and leflunomide (LEF).Methods:The study used data from 7 databases from 4 countries: CCAE, MDCR, Optum, IQVIA Ambulatory EMR (US); IQVIA THIN IMRD EMR (UK); IQVIA Disease Analyzer EMR (Germany); and SIDIAP (Spain). Cohorts included adult patients with a diagnosis of RA from 2005 to 2019 with at least one-year prior follow-up, no prior inflammatory arthritis, initiaton of first-line csDMARD, and no cytopenia in the preceding 30 days. Participants were followed from one day after treatment initiation to the earliest of event occurrence, treatment discontinuation/switching plus 14 days in the on-treatment analysis, five years in the intent-to-treat (ITT) analysis, or loss to follow-up. MTX was used as reference group. Cox models were fitted with propensity score stratification for observed confounding and negative control outcomes calibration for residual error. Estimates across database were pooled where I2Results:Overall 166,347 patients were included. Pooled rates of leukopenia and pancytopenia for MTX were 10.9 and 3.2 per 1,000 person years, respectively. Figure 1 and 2 show the results for the different databases and pooled estimates where applicable. Database estimates are not reported where adequate covariate balance not attained, and meta-analysis not shown where I2>0.4. MTX showed slightly higher hazards of leukopenia and of pancytopenia compared to LEF but no consistently differential risks compared to HCQ or SSZ.Figure 1.Calibrated hazard ratios (95% CI) vs MTX, on-treatment analysisConclusion:Cytopaenia is rare, and apparently more frequent with MTX and less with LEF. Since prior full blood counts were inconsistently obtained in fewer than 50% of csDMARD new users (e.g. more frequent in MTX [42%] than HCQ [32%] in CCAE and Optum; roughly equal in MDCR), these results should inform future monitoring recommendations.Figure 2.Calibrated hazard ratios (95% CI) vs MTX, ITT analysisDisclosure of Interests:Loreto Carmona Grant/research support from: Novartis Farmaceutica, SA, Pfizer, S.L.U., Merck Sharp & Dohme España, S.A., Roche Farma, S.A, Sanofi Aventis, AbbVie Spain, S.L.U., and Laboratorios Gebro Pharma, SA (All trhough institution), James Weaver Shareholder of: J&J Shares, Grant/research support from: Full-time employment salary from Janssen, Consultant of: Janssen employee, Employee of: Janssen, Paid instructor for: Janssen employee, have instructed at conferences, Speakers bureau: Janssen employee, have spoken at conferences, Edward Burn: None declared, Ben Illingens: None declared, David Vizcaya Employee of: Bayer, Ruta Sawant Shareholder of: AbbVie, Employee of: AbbVie, Talita Duarte-Salles: None declared, Patrick Ryan: None declared, Daniel Prieto-Alhambra Grant/research support from: Professor Prieto-Alhambra has received research Grants from AMGEN, UCB Biopharma and Les Laboratoires Servier, Consultant of: DPA’s department has received fees for consultancy services from UCB Biopharma, Speakers bureau: DPA’s department has received fees for speaker and advisory board membership services from Amgen

Background:The lifetime prevalence of lower back pain is between 60% and 70%, with surgical treatments spared for those not responding to other options.Objectives:To investigate the age, gender and socio-economic status differences in back pain procedures in the UK between 2000, 2008 and 2016.Methods:Data was obtained from primary care electronic medical records (CPRD GOLD) linked to English hospital admissions data. Lower back procedures in patients aged 35+ were identified using OPCS-4 codes for Decompression (Dc), Fusion (F), Therapeutic injections (TI) and Denervation (Dn). Standardised incidence rates (IR) of each type of lower back procedures were calculated per 10,000 CPRD registered person years for each age group, gender, region and SES strata in 2000, 2008 and 2016. IR were also calculated for combinations of age and gender. Negative binomial regression calculated incidence rate ratios (IRR) and 95% confidence intervals.Results:The IR of lower back procedures was 21.5 [20.7, 22.3] per 10,000 person years in 2000. This doubled by 2008 (45.5 [44.5, 46.5]) and trebled by 2016 (62.5 [60.8, 64.2]). Number of events and incidence rates of each procedure type are shown in table 1 below. The incidence of Dn has increased 6-fold whilst Dc and F have doubled. Female (IR in 2016 of 73.99 [71.43, 76.61] vs 50.08 [47.90, 52.33] in men, IRR 1.50 [1.41, 1.59]) and age are associated with back procedure rates (figure 1). Large socio-economic differences were observed, with higher procedure rates seen in the most deprived areas. These differences did however narrow over time during the study period (figure 2).Table 1.Event numbers and incidence rates of different types of lower back procedure.FusionDecompressionTherapeutic InjectionDenervationEventsIR (95% CI)EventsIR (95% CI)EventsIR (95% CI)EventsIR (95% CI)20001090.86 (0.71, 1.04)4663.69 (3.36, 4.04)203516.11 (15.42, 16.82)910.72 (0.58, 0.88)20083331.77 (1.58, 1.97)11976.35 (6.00, 6.72)628333.35 (32.53, 34.18)5963.16 (2.91, 3.43)20161591.93 (1.65, 2.26)5256.39 (5.85, 6.96)386547.03 (45.56, 48.54)4875.93 (5.41, 6.48)Figure 1.Age and Gender stratified incidence rate ratios of all back procedures in 2000, 2008 and 2016Figure 2.Deprivation status incidence rate ratios by yearConclusion:The incidence of lower back procedures has more than trebled since 2000. Women are more likely to have lower back procedures than men, with patients aged 65-74 the most likely to have a procedure. Procedures in those aged 75+ have become more common over time, potentially increasing the risk of post-operative complications. Socio-economic differences in the incidence of low back procedures are probably related to the known higher prevalence of back pain in deprived areas. Whether the observed narrowing in socio-economic variation over time is explained by a reduced need or by lowered provision needs further research.Disclosure of Interests:Danielle E Robinson: None declared, Jennifer Lane: None declared, Richard Craig: None declared, Andrew Judge: None declared, James Bailey: None declared, Dahai Yu: None declared, Kelvin Jordan: None declared, George Peat: None declared, Ross Wilkie: None declared, Alan Silman: None declared, Victoria Y Strauss: None declared, Daniel Prieto-Alhambra Grant/research support from: Professor Prieto-Alhambra has received research Grants from AMGEN, UCB Biopharma and Les Laboratoires Servier, Consultant of: DPA’s department has received fees for consultancy services from UCB Biopharma, Speakers bureau: DPA’s department has received fees for speaker and advisory board membership services from Amgen

Background:Recent studies show possible mechanisms of microbiota alterations that lead to the development of Ankylosing spondylitis (AS). These disturbances in the microbiota can be caused by long-term and high dose intake of antibioticsObjectives:To analyze the association between antibiotic/s use and the risk of developing AS.Methods:Population based case-control study using electronic medical records data from SIDIAP, covering >80% of the population in Catalonia, Spain. AS diagnoses with 2+ years data available were matched to up to 5:1 controls of same age, sex, and GP practice, and similar follow-up. Tracking of antibiotic use in the previous two years was done through pharmacy dispensation data standardized with ATC codes, and categorized in terms of recency of use and quartiles of cumulative dose. Adjusted odds ratios were estimated using conditional logistic regression analyzing antibiotic use (yes/no), recency of intake (current, recent, past, no use) and cumulative dose (quartiles of daily defined doses in the previous two years). All analyses were adjusted for age, body mass index, smoking, co-morbidity, socio-economic deprivation and number of GP visits as a proxy for healthcare resource use.Results:The study included 4,493 cases diagnosed with AS and 22,016 controls. 46.3% of cases and 28.2% of controls had taken antibiotics. An association between taking beta-lactams (OR 1.18 [95% CI: 1.09-1.28]) and taking macrolides (OR 1.34 [95% CI: 1.18-1.52]) and getting diagnosed with AS was found. This association was stronger with current/recent use (Figure 1), but no dose-response pattern was seen (Figure 2).Figure 1.Recency of use and AS diagnosis.Figure 2.Cumulative use and AS diagnosisConclusion:There is an association between use of certain types of antibiotics and the diagnosis of AS, but no dose-response gradient. These data do not support a causal effect of cumulative antibiotic use on the development of AS. More research is needed on the impact of microbiome disturbance on the risk of developing AS.Acknowledgments:Partial support received from the Oxford NIHR Biomedical Research Centre (BRC)Disclosure of Interests:Ana Pascual-Dapena: None declared, Albert Prats-Uribe: None declared, Daniel Prieto-Alhambra Grant/research support from: Professor Prieto-Alhambra has received research Grants from AMGEN, UCB Biopharma and Les Laboratoires Servier, Consultant of: DPA’s department has received fees for consultancy services from UCB Biopharma, Speakers bureau: DPA’s department has received fees for speaker and advisory board membership services from Amgen

Background:The COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus is of particular concern for people with rheumatoid arthritis (RA), with concerns that these people may be at higher risk and have poorer outcomes. However, at present the implications of COVID-19 for people with RA remain poorly understood.Objectives:To investigate the associations between rheumatoid arthritis and the risk of COVID-19 diagnosis, hospitalisation with COVID-19 and COVID-19-related death.Methods:A population-based cohort study including all individuals registered in the Information System for Research in Primary Care (SIDIAP). SIDIAP includes primary care records covering over 80% of the population of Catalonia, Spain, and was linked to region-wide SARS-CoV-2 PCR testing, hospital and mortality records. Outpatient diagnoses of COVID-19, hospitalisations with COVID-19 and deaths with COVID-19 were identified as study outcomes between 1st March and 6th May 2020. A multi-state model was used, with cause-specific Cox survival models estimated for each transition, adjusted for age and sex.Results:A total of 5,586,565 individuals were identified in SIDIAP as of the 1st March 2020, of which 16,344 had RA. RA patients were median (IQR) 63 years (52.0, 74.0) and the majority (n=11,727, 71.8%) were female. Having RA was positively associated with being diagnosed with COVID-19 (adjusted HR 1.14 (1.03 to 1.28)), with hospitalisation with COVID-19 (HR 1.66 (1.35 to 2.04)). However, we did not find an association between RA status and the risk of worsening from outpatient diagnosis to hospitalization or death, or from hospitalization to death (see Table 1).Table 1.Estimated hazard ratios, adjusted for age and gender, for individuals with rheumatoid arthritisTransitionStudy population (RA), nTotal events (RA), nHazard Ratios(95% Confidence Intervals)From general population to diagnosed with COVID-195,586,565 (16,344)88,396 (324)1.14 (1.03 to 1.28)From general population to hospitalised with COVID-195,586,565 (16,344)10,143 (90)1.66 (1.35 to 2.04)From diagnosed with COVID-19 to hospitalised with COVID-1988,396 (324)5,946 (30)0.95 (0.66 to 1.36)From diagnosed with COVID-19 to death88,396 (324)2,295 (16)0.96 (0.58 to 1.56)From hospitalised with COVID-19 to death16,089 (120)2,602 (27)1.13 (0.77 to 1.64)Conclusion:To our knowledge, this is the largest study performed to date looking at COVID-19 outcomes in RA patients. Individuals with RA were found to have an increased risk of COVID-19 diagnosis and hospitalisation with COVID-19, compared to the general population. Further research is needed to address factors associated with this including the presence of other co-morbidities, underlying RA disease activity and the use of immunosuppressive medications.Disclosure of Interests:Arani Vivekanantham: None declared, Edward Burn: None declared, Sergio Fernandez-Bertolin: None declared, Maria Aragon: None declared, Talita Duarte-Salles: None declared, Daniel Prieto-Alhambra Grant/research support from: Dr. Prieto-Alhambra reports grants and other from AMGEN, grants, non-financial support and other from UCB Biopharma, grants from Les Laboratoires Servier, outside the submitted work; and Janssen, on behalf of IMI-funded EHDEN and EMIF consortiums, and Synapse Management Partners have supported training programmes organised by DPA’s department and open for external participants.

Background:Osteoarthritis (OA) is the most common form of arthritis and a major cause of pain and disability worldwide. Individuals with OA have increased cardiovascular morbidity and mortality, and other comorbidities are also more common amongst them than in the general population. In this study, we examined the prevalence and timing of the diagnosis of co-morbidities prior to the clinical diagnosis of OA.Objectives:To determine the odds of comorbidities in newly diagnosed OA cases versus matched controls in the up to 10 years prior to diagnosis.Methods:Case-control study of people registered in the Information System for Research in Primary Care (SIDIAP). SIDIAP includes primary care records covering over 80% of the population of Catalonia, Spain.Participants with an incident diagnosis of OA, based on ICD-10-CM disease codes, were matched to up to 4 controls by age (within 2 years), gender and primary care practice. The first diagnosis date of OA used the index date, with matched controls using the same index date, to retrospectively review for comorbidities. Patients were required to have at least 3 years continuous registration prior to the index date. A total of 57 comorbidities were considered, based on prior knowledge and clinical consensus.Descriptive statistics were used to obtain the demographic information about cases and controls. Counts of any comorbidity were calculated, and univariable and multivariable logistic regression were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) of individual comorbidities adjusted for age, gender and socio-economic status.Results:In total, there were 455,494 OA cases and 1,481,298 matched controls. The cases and controls were similar with regards to age, gender and deprivation level.The incident diagnosis of any comorbidity at any time prior to index date was 77% (n= 350,913) in cases versus 61% (n= 909,497) in controls.The results from the multivariable analysis [Table 1] showed that OA patients had higher prevalence of many comorbidities up to 1 year prior to their diagnosis of OA compared to up to 10 years prior to diagnosis. They were most likely to be diagnosed with another musculoskeletal condition followed by neuro-psychiatric and metabolic and cardiovascular conditions. Conversely, patients with OA were less likely to be diagnosed with cancer up to 10 years prior to index date than matched controls.Table 1.Multivariable analysis at 1 year and 10 year prior to index dateCo-morbidityMultivariable analysis 1-year prior (OR, 95% CI)Multivariable analysis 10-year prior (OR, 95% CI)Musculoskeletal conditionsAnkylosing Spondylosis3.12 (2.41, 4.05)1.27 (1.12, 1.43)Fibromyalgia4.24 (3.96, 4.54)1.85 (1.80, 1.91)Rheumatoid Arthritis2.67 (2.40, 2.97)1.27 (1.20, 1.34)Back/ neck pain2.41 (2.38, 2.45)1.76 (1.75, 1.78)Neuro-psychiatricAnxiety1.69 (1.65, 1.73)1.23 (1.22, 1.24)Depression1.87 (1.81, 1.93)1.25 (1.24, 1.27)Irritable Bowel Syndrome1.90 (1.71, 2.11)1.28 (1.22, 1.34)Migraine1.81 (1.69, 1.94)1.23 (1.20, 1.27)CancerLeukaemia1.07 (0.88, 1.30)0.91 (0.82, 1.00)Lymphoma0.84 (0.68, 1.03)0.90 (0.82, 0.99)Solid malignancy0.95 (0.91, 0.99)0.95 (0.93, 0.97)Other medical conditionsStroke1.15 (1.10, 1.20)0.95 (0.93, 0.97)Hypertension1.70 (1.68, 1.74)1.26 (1.25, 1.28)Diabetes1.34 (1.30, 1.38)1.07 (1.06, 1.09)Obesity1.96 (1.92, 2.01)1.60 (1.58, 1.62)Conclusion:Patients with OA have multiple chronic conditions. Our results found that the diagnosis of these other co-morbidities (particularly musculoskeletal and neuro-psychiatric conditions) were more likely to occur in the 1-year prior to their diagnosis of OA, compared to in the 10-year prior, except for lymphoma and solid malignancy. These results help us to further understand the relationship and timing of the development of multiple co-morbidities in patients with OA.Disclosure of Interests:Arani Vivekanantham: None declared, Daniel Prieto-Alhambra: None declared, Danielle E Robinson Grant/research support from: Dr. Prieto-Alhambra reports grants and other from AMGEN, grants, non-financial support and other from UCB Biopharma, grants from Les Laboratoires Servier, outside the submitted work; and Janssen, on behalf of IMI-funded EHDEN and EMIF consortiums, and Synapse Management Partners have supported training programmes organised by DPA’s department and open for external participants.

Background:The Observational and Medical Outcomes Partnerships (OMOP) common data model (CDM) provides a framework for standardising health data with a view towards federated analyses, thus maximising the use and power of combining disparate datasets.Objectives:To assess feasibility and usefulness of mapping biologic registry data from different European countries to the OMOP CDM and present initial descriptive data regarding comorbidities.Methods:Five biologic registries, as part of a funded FOREUM project, have been mapped to the OMOP CDM: 1) the Czech biologics register (ATTRA), 2) Registro Español de Acontecimientos Adversos de Terapias Biológicas en Enfermedades Reumáticas (BIOBADASER), 3) British Society for Rheumatology Biologics Register for Rheumatoid Arthritis (BSRBR-RA), 4) German biologics register ‘Rheumatoid arthritis observation of biologic therapy’ (RABBIT), and 5) Swiss register ‘Swiss Clinical Quality Management in Rheumatic Diseases’ (SCQM). The mapping includes socio-demographic, observation period within the studies, baseline comorbidities, and baseline medications. Only patients with RA were included. Using R, registers received identical scripts to run on their mapped databases to produce an initial description of patient characteristics without the need to share patient-level data.Results:A total of 54,458 individuals are included the five registries being mapped to the OMOP CDM, see table. Age and gender distribution was similar across registries. All registers reported on cardiovascular system comorbidities, diabetes mellitus, mental disorders, and respiratory system comorbidities. However, it was noted that results of comorbidity mapping relies on what each register collect on each patient at the point of registration.Whilst the Charlson comorbidity index could be calculated within each registry, due to lack of the specific coding needed, such as “uncomplicated diabetes mellitus” / “end-organ damage diabetes mellitus”, it was felt to be an inaccurate measure. The granularity of the comorbidities was insufficient, as many registers coded, for example, diabetes mellitus without any extra information.Table 1.OARSI scoresRegistryATTRABIOBADASERBSRBR-RARABBITSCQMCountryCzechiaSpainUnited KingdomGermanySwitzerlandNumber of Participants23343012251791365210281Gender FemaleMale1808 (77%)526 (23%)2372 (79%)640 (21%)18995 (75%)6184 (25%)10191 (75%)3461 (25%)7584 (74%)2697 (26%)Age at observation start date59 (52, 66)56 (47, 63)58 (49, 66)58 (50, 67)57 (47, 66)First observation start dateFeb-2002Oct-1999Oct-2001Aug-2006March-1995Number of comorbidities1 (1, 2)1 (0, 2)1 (0, 2)2 (1, 3)2 (1, 4)Disorder of cardiovascular system1609 (69%)208 (7%)2239 (9%)6330 (46%)3969 (39%)Diabetes mellitus331 (14%)273 (9%)1770 (7%)1591 (12%)792 (8%)Depressive Disorder165 (7%)04971 (20%)1023 (7%)1337 (13%)Disorder of respiratory system215 (9%)209 (7%)4125 (16%)1282 (9%)1630 (16%)Conclusion:This is the first analysis of data from the newly mapped OMOP CDM across five European registers. Through mapping the registers into a CDM, and using the same script, the ability to undertake collaborative analysis without sharing patient level data outside of the country can be realised. Due to differences in study design and data capture, there needs to be a focus on harmonising the coding and analysing of the comorbidities and drugs across registries.Disclosure of Interests:Lianne Kearsley-Fleet: None declared, Kimme Hyrich: None declared, Martin Schaefer: None declared, Doreen Huschek: None declared, Anja Strangfeld: None declared, Jakub Zavada Speakers bureau: Abbvie, Eli-Lilly, UCB, Sanofi., Consultant of: Abbvie, UCB, Sanofi, Gilead., Markéta Lagová: None declared, Delphine Courvoisier Speakers bureau: Medtalks Switzerland, Christoph Tellenbach: None declared, Kim Lauper Speakers bureau: Medtalks Switzerland, Carlos Sánchez-Piedra: None declared, Nuria Montero: None declared, Jesús-Tomás Sánchez-Costa: None declared, Daniel Prieto-Alhambra Consultant of: Amgen (speaker fees and advisory board membership fees paid to DPA’s department) and UCB (consultancy fees paid to DPA’s department), Grant/research support from: grants and other from AMGEN, grants, non-financial support and other from UCB Biopharma, grants from Les Laboratoires Servier, outside the submitted work., Edward Burn: None declared

Background:Treatment guidelines recommend early initiation of csDMARDs following diagnosis of rheumatoid arthritis (RA), with methotrexate (MTX) as first-line therapy. Scarce evidence exists on adherence to this guidanceObjectives:To characterize first-line csDMARD treatment during the first year following an RA diagnosis.Methods:14 real world databases (3 Primary care, 6 primary/secondary care records, 5 claims) from 9 countries were included, all mapped to the OMOP common data model.Patients were included on the earliest event of: 1st diagnosis of RA or 1st DMARD prescription with an RA diagnosis within 30 days. Patients were >18 years-old, required 1+ year pre-index data, and at least 1-year follow-up. Study period covered 2000-2018. Previous users of DMARDs or non-RA inflammatory arthritis history were excluded. Only MTX, Hydroxychloroquine (HCQ), Sulfasalazine (SSZ) and Leflunomide (LEF) were available in all databases.Results:We identified 323,547 eligible participants. Large variation was observed internationally (Figure 1). MTX as first-line monotherapy ranged from 33.3% to 74.5%, and in combination with HCQ from 2.1% to 6.7%. Three additional csDMARDs were used as first-line: HCQ in 10.1% to 30.2%, SSZ in 0.9% to 28.7%, and LEF in 1.8% to 15.2%.Figure 1.First line csDMARD treatment during 1yr from first observed RA diagnosisConclusion:We report wide heterogeneity of first-line csDMARDs regimens internationally. Despite recommendations for MTX to be first line therapy, data suggest that a large proportion of patients receive alternative csDMARD.Disclosure of Interests: :Anthony G Sena Shareholder of: J&J shares, Grant/research support from: Full-time employment salary from Janssen, Consultant of: Full-time employment salary from Janssen, Employee of: Janssen employee, Paid instructor for: Janssen employee, Speakers bureau: Janssen employee, Denis Granados: None declared, Nigel Hughes Shareholder of: J&J shares, Grant/research support from: Full-time employment salary from Janssen, Consultant of: Janssen employee, Employee of: Janssen employee, Paid instructor for: Janssen employee, Speakers bureau: Janssen employee, WALID FAKHOURI Shareholder of: E Lilly Shares, Employee of: Eli Lilly and Company, Antje Hottgenroth Shareholder of: Eli Lilly shares, Employee of: Lilly Deutschland GmbH, Raivo Kolde: None declared, Sulev Reisberg: None declared, Carmen Olga Torre: None declared, Talita Duarte-Salles: None declared, Yesika Díaz: None declared, Jose Felipe Golib-Dzib Grant/research support from: Full-time employment salary from Janssen, Employee of: Yes, Janssen employee, Paid instructor for: Janssen Employee, Speakers bureau: Janssen Employee, Emily S. Brouwer Shareholder of: J&J shares, Takeda shares, Grant/research support from: Full-time employment salary from Janssen, Consultant of: Janssen employee, Employee of: Janssen employee, Paid instructor for: Janssen Employee, Speakers bureau: Janssen Employee, Edward Burn: None declared, Jennifer Lane: None declared, David Vizcaya Employee of: Bayer, Sara Bruce Wirta Employee of: Janssen-Cilag Sweden AB, Marcel de Wilde: None declared, Katia Verhamme: None declared, Peter Rijnbeek: None declared, Elke Theander Employee of: Janssen-Cilag Sweden AB, Katerina Chatzidionysiou Consultant of: AbbVie, Pfizer, Lilly., Daniel Prieto-Alhambra Grant/research support from: Professor Prieto-Alhambra has received research Grants from AMGEN, UCB Biopharma and Les Laboratoires Servier, Consultant of: DPA’s department has received fees for consultancy services from UCB Biopharma, Speakers bureau: DPA’s department has received fees for speaker and advisory board membership services from Amgen, Patrick Ryan: None declared

Background:EULAR guidelines recommend the early initiation of methotrexate (MTX) monotherapy as soon as possible after the diagnosis of rheumatoid arthritis (RA). Evaluating patient-level risks for adverse outcomes after MTX initiation would allow clinicians to provide more personalised care.Objectives:To develop and validate patient-level prediction models for adverse health outcomes including leukopenia, pancytopenia, infection (serious, opportunistic, all), cardiovascular disease (CVD) (myocardial infarction (MI), stroke), and cancer (breast, colorectal, uterus) in adult RA patients initiating first-line treatment of MTX monotherapyMethods:Health data from claims and electronic health records were used including patients from 7 European countries (Spain, Estonia, Netherlands, Belgium, Germany, France, and the UK), the United States of America, Australia, and Japan. All RA patients initiating first-line treatment of MTX monotherapy with at least one year of prior observation were included. Prediction models for the outcomes were developed for a time at risk of 3 months (infections, leukopenia, pancytopenia), 2 years (MI and stroke), and 5 years (cancers) on the Optum© De-Identified Clinformatics® Data Mart Database. Models were developed using LASSO logistic regression and were evaluated using the area under the receiver operator characteristic curve (AUROC) for discrimination and graphically assessed for calibration. The models were externally validated on all other databases.Results:A total of 21,307 subjects were used for training and validated against 143,427 patients from 14 sites. MI (AUROC internal 0.77, AUROC external ranging from 0.49 to 0.78), stroke (AUROC internal 0.78, AUROC external ranging from 0.68 to 0.79) and serious infection (AUROC internal 0.75, AUROC external ranging from 0.63 to 0.79) had good predictive validity [Table 1]. Discrimination for all other outcomes was lower, with all AUChttps://data.ohdsi.org/ehdenRaPrediction/Table 1.Internal (Optum) and external validation results: AUC ROC for discriminationDatabaseAcute MI within 2yStroke within 2ySerious Infection within 3mOptum (internal)0.770.780.75PanTher0.760.780.74IQVIA_AMBEMR0.760.72CCAE0.730.730.66IQVIA_GERMANY0.640.70IQVIA_THIN0.620.65MDCR0.680.680.67IQVIA_HOSPITAL0.670.630.61MDCD0.720.790.63JMDC0.490.750.71IQVIA_LPDFRANCE0.69Estonia0.670.770.82IQVIA_AUS0.58IPCI0.68SIDIAP0.650.75Conclusion:Clinical tools were developed that successfully identify subjects at risk of MI, stroke and serious infection at the initiation of first-line MTX therapy. The developed algorithms had good transportability and generally, the models with high AUROC had adequate internal calibration although some external validations show they could benefit from recalibration. For short-term opportunistic and all infections, as well as 5-year cancer models, we were unable to achieve a high enough AUROC to warrant validating externally.Disclosure of Interests:Cynthia Yang: None declared, Ross Williams: None declared, Joel Swerdel Shareholder of: J&J shares, Grant/research support from: Full-time employment salary from Janssen, Consultant of: Janssen employee, Employee of: Janssen, Paid instructor for: Janssen employee, have instructed at conferences, Speakers bureau: Janssen employee, have spoken at conferences, Meghna Jani Speakers bureau: Grifols, Talita Duarte-Salles: None declared, Katerina Chatzidionysiou Consultant of: AbbVie, Pfizer, Lilly., Daniel Prieto-Alhambra Grant/research support from: Professor Prieto-Alhambra has received research Grants from AMGEN, UCB Biopharma and Les Laboratoires Servier, Consultant of: DPA’s department has received fees for consultancy services from UCB Biopharma, Speakers bureau: DPA’s department has received fees for speaker and advisory board membership services from Amgen, Patrick Ryan: None declared, Peter Rijnbeek: None declared

Background:Conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) are recommended as first line treatment for rheumatoid arthritis (RA) patients, but limited information exists on the comparative risk of cancer associated with their use.Objectives:To compare the risk of incident overall (excluding non-melanoma skin) and site-specific cancers (colorectal, lung, lymphoma, leukaemia) associated with first-line use of csDMARDs in patients with RA.Methods:We conducted a multinational cohort study informed by data from 7 healthcare databases including claims and electronic medical records from 4 countries (SIDIAP-Spain, MDCR-US Optum-US, CCAE-US, IQVIA AMBEMR-US, IQVIA-Germany, THIN-UK) part of the Observational Health Data Sciences and Informatics (OHDSI) network. All patients aged ≥18 years who initiated methotrexate (MTX), hydroxychloroquine (HCQ), sulphasalazine (SSZ), or leflunomide (LEF) as first-line monotherapy after a diagnosis of RA between 2005 to 2018 were eligible. Individuals with a prior diagnosis of another inflammatory arthropathy or cancer, or 2Results:Across the databases, 127,547 RA patients initiating csDMARD therapy were included in the analyses (MTX: 73,996, HCL: 36,381 SSZ: 9,383 LEF: 7,787). The pooled incidence rate of overall cancer for MTX was 22.8 per 1,000 person years. The pooled summary and source-specific estimated cHRs for overall cancer are shown below in Figure 1. While little difference was seen for HCQ and SSZ compared to MTX, LEF was consistently associated with a reduced cancer risk: pooled cHR (95% CI) 0.67 (0.59 to 0.76) and cHRs ranged from 0.53 (0.36 to 0.80) in CCAE-US to 0.84 (0.58 to 1.22) in SIDIAP-Spain. There were insufficient cases to look site-specific cancers within data sources, although pooled results suggest little risk difference in leukemia, lymphoma, colorectal, or lung cancers.Figure 1.Calibrated hazard ratios (cHRs) of overall cancer risk with their respective confidence intervals (95%CI) by study database. Database estimates not reported where adequate covariate balance not attained. Meta-analysis results not reported where I2>0.4.Conclusion:Compared to MTX users, patients treated with LEF had a lower risk of overall cancer. Risk of four specific cancers did not differ by first line csDMARD exposure.Disclosure of Interests: :Talita Duarte-Salles: None declared, Martina Recalde: None declared, James Weaver Shareholder of: J&J Shares, Grant/research support from: Full-time employment salary from Janssen, Consultant of: Janssen employee, Employee of: Janssen, Paid instructor for: Janssen employee, have instructed at conferences, Speakers bureau: Janssen employee, have spoken at conferences, Edward Burn: None declared, Karine Marinier Employee of: Servier, Yesika Díaz: None declared, Ben Illingens: None declared, David Vizcaya Employee of: Bayer, Katerina Chatzidionysiou Consultant of: AbbVie, Pfizer, Lilly., Patrick Ryan: None declared, Daniel Prieto-Alhambra Grant/research support from: Professor Prieto-Alhambra has received research Grants from AMGEN, UCB Biopharma and Les Laboratoires Servier, Consultant of: DPA’s department has received fees for consultancy services from UCB Biopharma, Speakers bureau: DPA’s department has received fees for speaker and advisory board membership services from Amgen

Background:Opioids are not recommended as first-line treatments for chronic pain management in osteoarthritis (OA), but recent data suggest they are commonly used in routine practice in North America and northern Europe.Objectives:To characterise the secular trends of opioid and strong opioids use in patients with incident OA from 2007 to 2016, and to explore the impact of patient characteristics on the use of opioid/s for OA.Methods:Data was obtained from the SIDIAP (The System for the Development of Research in Primary Care) database, which contains primary care records and pharmacy dispensing data for 80 % of the population in Catalonia (~ 6 million people). All persons aged 18 or older at the beginning of each calendar year with an incident OA diagnosis (including both peripheral and central joints) in the study period were included. Index date was the date of first OA diagnosis, and the observation period of opioid use was 1-year after index date. Opioids considered included codeine, tramadol, fentanyl, and morphine, with the latter three classified as strong opioids. The period prevalence of any opioid use was estimated in whole and sub-population stratified by sex, age, socio-economic status (U1 – U5, higher values of the indicator equivalent to deprivation) and residence area (rural/urban).Results:The 1-year prevalence of any opioid use among incident OA patients was around 15% from 2007 to 2012. After that, this figure grew by 10% approaching 25% in 2016. However, strong opioid use increased continuously to nearly triple, from 8% in 2007 to 20% in 2016. The different subgroups followed similar trends over time, with women 4% higher than men, oldest 10% higher than youngest, most deprived 6% higher than least deprived, and rural 1% higher than urban.Conclusion:The use of opioids (and especially strong opioids) has substantially increased in recent years among newly diagnosed OA patients in Catalonia. Our findings call for urgent action for safe opioid prescribing to avoid opioid abuse in OA patients especially amongst older women living in deprived areas.Figure 1.Trends of 1-year prevalence of opioid/s use among incident OA patients, whole and subgroup population.Disclosure of Interests:Junqing Xie: None declared, Aleksandra Turkiewicz: None declared, Gary Collins: None declared, Martin Englund Consultant of: Advisory Board 1 day (2019) Pfizer (Tanezumab)., Victoria Y Strauss: None declared, Carlen Reyes: None declared, Daniel Prieto-Alhambra Grant/research support from: Professor Prieto-Alhambra has received research Grants from AMGEN, UCB Biopharma and Les Laboratoires Servier, Consultant of: DPA’s department has received fees for consultancy services from UCB Biopharma, Speakers bureau: DPA’s department has received fees for speaker and advisory board membership services from Amgen

Background:RA is associated with an increased cardiovascular (CV) risk. csDMARDs are first-line treatments for RA and can mitigate this risk, but limited data exist on their CV effects. Previous trials have reported protective effects for methotrexate (MTX) and hydroxychloroquine (HCQ), but no similar data exist on sulfasalazine (SSZ) or leflunomide (LEF).Objectives:To assess the comparative effect of csDMARDs on the risk of myocardial infarction (MI) and stroke in RA patientsMethods:Data from 6 claims/electronic health records databases across Germany, US, and UK, all mapped to the Observational Medical Outcomes Partnership (OMOP) common data model. A cohort study was conducted including patients ≥18 years old, with first RA diagnosis in 2005-2019, initiating csDMARD monotherapy with MTX, HCQ, SSZ, or LEF. Those with a prior diagnosis of other inflammatory arthritis or 2for heterogeneity Results:145,248 patients were included (MTX: 73,996, HCQ: 49,752, SSZ: 12,256, LEF: 9,244). Pooled rates of MI and stroke for MTX were 7.64 and 10.26 per 1,000 person years respectively. Detailed estimate cHRs are shown in Figure 1 for the intention to treat analysis. MI risk with SSZ and LEF was comparable to MTX. Risk of stroke was similar between LEF and MTX, but reduced for HCQ and SSZ compared to MTX, with pooled cHR (95% CI) 0.86 (0.78 to 0.95) and 0.71 (0.52 to 0.98) for HCQ and SSZ respectively. Similar results were found for “on treatment” analyses.Figure 1.Calibrated hazard ratios (cHRs) for MI and strokeConclusion:Overall, all four csDMARDs had similar effects on MI risk. HCQ and SSZ use were associated with a decreased risk of stroke compared to MTX. The observed differences may be attributable to differential effects on the atherosclerotic process, differential disease control, or both.Database estimates not reported where adequate covariate balance not attained. Meta-analysis results not reported where I2>0.4. MEDICARE did not pass diagnostics for SSZ and LEF analyses. cHR: calibrated Hazard Ratio; CI: Confidence Interval; MTX: Methotrexate; HCQ: Hydroxychloroquine; SSZ: sulphasalazine; LEF: Leflunomide; THIN: The Health Improvement Network (UK); Optum: Optum de-identified Clinformatics Datamart (US); MDCR: Medicare (US); GERMANY: IQVIA Disease Analyzer EMR (Germany); CCAE: IBM MarketScan Commercial Claims and Encounters (US); AMBEMR: IQVIA Ambulatory EMR (US)Database estimates not reported where adequate covariate balance not attained. Meta-analysis results not reported where I2>0.4. MEDICARE did not pass diagnostics for SSZ and LEF analyses. cHR: calibrated Hazard Ratio; CI: Confidence Interval; MTX: Methotrexate; HCQ: Hydroxychloroquine; SSZ: sulphasalazine; LEF: Leflunomide; THIN: The Health Improvement Network (UK); Optum: Optum de-identified Clinformatics Datamart (US); MDCR: Medicare (US); GERMANY: IQVIA Disease Analyzer EMR (Germany); CCAE: IBM MarketScan Commercial Claims and Encounters (US); AMBEMR: IQVIA Ambulatory EMR (US)Disclosure of Interests: :Albert Prats-Uribe: None declared, Ben Illingens: None declared, David Vizcaya Employee of: Bayer, James Weaver Shareholder of: J&J Shares, Grant/research support from: Full-time employment salary from Janssen, Consultant of: Janssen employee, Employee of: Janssen, Paid instructor for: Janssen employee, have instructed at conferences, Speakers bureau: Janssen employee, have spoken at conferences, Edward Burn: None declared, Ruta Sawant Shareholder of: AbbVie, Employee of: AbbVie, Karine Marinier Employee of: Servier, Patrick Ryan: None declared, Daniel Prieto-Alhambra Grant/research support from: Professor Prieto-Alhambra has received research Grants from AMGEN, UCB Biopharma and Les Laboratoires Servier, Consultant of: DPA’s department has received fees for consultancy services from UCB Biopharma, Speakers bureau: DPA’s department has received fees for speaker and advisory board membership services from Amgen

Background:Osteoarthritis (OA) is associated with increased comorbidity, but knowledge of the temporal relationships between OA and comorbidities is limited.Objectives:To estimate the risk of consulting for comorbidities in people with incident clinician-diagnosed knee or hip OA.Methods:Using the Swedish Population Register, we identified all residents aged 35 years or above in the Skåne region, Sweden (total pop. 1.23 million) in the year 2009. We used the Skåne Health Care Register (SHR), a comprehensive register based on physicians’ International Classification of Disease (ICD) 10, to identify persons who had at least one diagnosis of knee or hip OA – the exposures of interest – and 18 other diagnoses (Figure 1) – the outcomes of interest – between 1 January 2010 and 31 December 2017. To minimize potential confounding due to propensity to seek care, persons had to have at least one health-care visit with any diagnosis registered between 1 January 1998 and 31 December 2009 to be included. We excluded persons with a knee or hip OA diagnosis before 1 January 2010, and for each analysis, persons with a previous diagnosis of the outcome diagnosis of interest. People were followed from 1 January 2010 until relocation outside of the region, death, outcome diagnosis, or 31 December 2017, whichever came first. We calculated hazard ratios (HR) of each outcome diagnosis using Cox proportional hazard models with incident knee and hip OA as time-varying exposure. Time from start of follow-up to the date of an OA diagnosis was treated as unexposed, while time from an OA diagnosis to the outcome diagnosis was treated as exposed. Models were adjusted for residential area, if born in Sweden, annual income, years of education, marital status, sex, and age (all retrieved from Statistics Sweden), and baseline conditions (i.e. the other outcome diseases of interest, and alcohol-related disorders) as registered in SHR before 1 January 2010.Results:We included 548,681 persons in the Skåne population having at least one health-care visit during 1998 to 2009 and no doctor-diagnosed knee or hip OA. Of these, 36,465 persons consulted for knee OA and 14,477 for hip OA during the follow-up period (Table 1). Persons with clinician-diagnosed incident knee or hip OA have 8-61% higher hazard of depression, cardiovascular diseases, back pain, and osteoporosis than persons without an OA diagnosis (Fig. 1). Both knee and hip OA persons have increased risk of diabetes, however the 95% confidence interval excluded 1 only for knee OA (Fig. 1). Also, only knee OA patients have an increased risk of fracture to the forearm. For the rest of the diagnoses, we found either no increased risk for knee or hip OA persons, or estimates with wide confidence intervals, excluding any clear interpretations of the direction or size of the effects.Table 1.Demographics of the study cohort at start of follow-up (Jan. 1, 2010).No OA(n=497,739)Incidentknee OA(n=36,465)Incidenthip OA(n=14,477)Age, yrs (SD)57.3 (14.6)62.2 (12.2)65.3 (11.7)Women, n (%)254,593 (51)21,553 (59)8,306 (57)Marrieda, n (%)350,172 (70)27,955 (77)10,937 (76)Born in Swedenb, n (%)422,713 (85)31,292 (86)12,949 (89)Educationc, n (%) 128,738 (26)11,364 (31)4,745 (33) 10-12 yrs222,147 (45)16,390 (45)6,050 (42) 13-14 yrs59,950 (12)3,908 (11)1,556 (11) ≥15 yrs83,620 (17)4,590 (13)2,065 (14)Income in 100,000 SEKd, mean (SD)2.3 (3.0)2.1 (2.4)2.1 (2.6)Missings:a29b44,c3,558,d2Conclusion:Incident clinician-diagnosed knee and hip OA are associated with increased risk of consultation for depression, cardiovascular disease, back pain, osteoporosis, and diabetes. Results support previous findings for cardiovascular diseases and diabetes, however suggesting that the risk of diabetes is mainly associated with knee OA.Acknowledgments:This study was supported by FOREUM.Disclosure of Interests:Kenneth Pihl: None declared, Aleksandra Turkiewicz: None declared, Velocity Hughes: None declared, Weiya Zhang Consultant of: Grunenthal for advice on gout management, Speakers bureau: Bioiberica as an invited speaker for EULAR 2016 satellite symposium, S.M.A. Bierma-Zeinstra Consultant of: From 2015-2017 for Infirst Healthcare, in 2019 for Phizer (consultancy fees were paid to the university), Daniel Prieto-Alhambra Grant/research support from: Professor Prieto-Alhambra has received research Grants from AMGEN, UCB Biopharma and Les Laboratoires Servier, Consultant of: DPA’s department has received fees for consultancy services from UCB Biopharma, Speakers bureau: DPA’s department has received fees for speaker and advisory board membership services from Amgen, Martin Englund Consultant of: Advisory Board 1 day (2019) Pfizer (Tanezumab).

Background Previous ecological data from the UK and Denmark suggest a decline in the incidence of joint replacements for RA patients following the introduction of tumour necrosis factor inhibitors (TNFi). However, patient-level data on the comparative effectiveness of TNFi compared to conventional synthetic DMARD (csDMARD) use on the need for total hip (THR) or knee (TKR) replacement are lacking. Objectives To estimate the impact of TNFi use on subsequent need for THR or TKR (primary outcomes) or other joint replacement (OJR) (secondary outcome) in RA. Methods A propensity score (PS) matched cohort was analysed using the British Society for Rheumatology Biologics Registry (2001 – 2016) for Rheumatoid Arthritis (BSRBR/RA) data. Exclusion criteria were: previous THR or TKR (all analyses) or OJR (secondary analysis), less than 6 months follow-up, prevalent biological DMARD use, or first biological DMARD use that was not a TNFi. Patients were followed from date of registration up to the earliest of date of outcome, death, loss-to-follow-up or change of TNFi exposure status (stopping, switching or starting). Multiple imputation was used to deal with missing data. The PS (i.e. the probability of receiving TNFi conditional on observed characteristics) was estimated using logistic regression. This included age, gender, ethnicity, index of multiple deprivation, BMI, smoking, year of registration, duration of RA, DAS-28, HAQ, SF36, ACR criteria, comorbidities, and comedications. A PS calliper of 0.2 was used to match all TNFi users to csDMARD users (with replacement) using a 1:1 ratio. Weighted Cox regression was used to estimate the impact of TNFi use on study outcomes, adjusted for any confounders that remained unbalanced. Results Our 1:1 matched cohort contained a total of 19 116 patient records. THR rate was 6.30/1,000 PYs [95% CI: 4.24 to 9.76] and 5.22/1,000 PYs [CI: 4.66 to 5.88] in the csDMARD and TNFi cohorts, respectively. TKR rate was 8.09/1,000 PYs [CI: 5.32 to 12.89] and 8.89/1,000 PYs [CI: 8.13 to 9.72], respectively. There was no significant association between TNFi use and THR or TKR (HRs=0.86 [CI: 0.60 to 1.22] and 1.11 [CI: 0.84 to 1.47], respectively), although when analyses were restricted to patients with DAS >5.1 (as per NICE guidance) these HRs were 0.74 [CI: 0.51–1.05] and 0.95 [CI: 0.71 to 1.26], respectively. Among those over 60 years old, TNFi was associated with a significant reduction in THR (HR=0.60 [CI: 0.41–0.87]) but not TKR (HR=1.31 [CI: 0.87–1.99]). THR but not TKR rates were also reduced among those with an above average HAQ score. Overall, no significant associations were found for OJR. Conclusions Our findings suggest TNFi use may reduce the need for THR in older and more severe RA patients, although no evidence was found for a reduction in younger or less severe patients or in rates of TKR or OJR. Further work is needed to confirm these results. Acknowledgements D.P.A. is funded by a National Institute for Health Research Clinician Scientist award (CS-2013–13–012). Disclosure of Interest S. Hawley: None declared, R. Cordtz: None declared, L. Dreyer Speakers bureau: UCB, MSD, C. Edwards Grant/research support from: Abbvie, BMS, Celgene, Pfizer, Biogen, Mundipharma, UCB, Roche, MSD, N. Arden Grant/research support from: BIOBERICA, Consultant for: BIOVENTUS, REGENERON and Smith and Nephew, C. Cooper: None declared, A. Judge: None declared, S. Ali: None declared, K. Hyrich: None declared, D. Prieto-Alhambra Grant/research support from: UCB, Amgen and Servier, Consultant for: UCB, Speakers bureau: Amgen

Background In addition to the possible carcinogenic effect of chronic inflammation, gout patients may experience increased risk of cancer due to additional risk factors such as obesity, diabetes, sedentary lifestyle, smoking and increased alcohol consumption. There is limited data on the association between gout and different cancer types. We investigated the incidence of cancer among Danish gout patients compared to national cancer rates. Methods All patients diagnosed with gout in the period 1978–2015 according to the Danish National Patient Registry (including in- and outpatient hospital contacts) were linked with The Danish Cancer Registry to identify incident cancers. Follow-up for cancer started at date of first gout diagnosis and ended at date of cancer, death, emigration or end of 2015, whichever came first. Standardised incidence ratios (SIR) were calculated using sex and 5 year age and calendar-specific incidence rates for first primary cancers in the general population in Denmark. Results We observed 6205 first primary cancers among 70 591 gout patients. Compared to an expected number of 5308 in the general population, this corresponded to a SIR for any-cancer of 1.17 (95% confidence interval (CI): 1.14–1.20). SIRs were highest for cancer sites associated with smoking, obesity and excess alcohol consumption: mouth/tongue, pharynx, oesophagus, liver, pancreas, lung, pleura and kidney (table 1). Excess risks were also observed for colorectal cancer, breast cancer, endometrial cancer, multiple myeloma and other types of leukaemia but not for Hodgkin and Non-Hodgkin lymphomas. Conclusions Gout patients are at risk of cancer, especially cancer types associated with smoking, obesity and excess alcohol consumption, but also multiple myeloma and leukaemia. It is unknown if uric-acid lowering therapy and/or lifestyle changes reduce this risk. Disclosure of Interest K. Zobbe: None declared, D. Prieto-Alhambra Grant/research support from: Amgen, Servier, and UCB, Consultant for: UCB, Speakers bureau: Amgen, R. Cordtz: None declared, L. Mellemkjaer: None declared, P. Hojgaard: None declared, L. E. Kristensen Grant/research support from: UCB, Biogen, Janssen pharmaceuticals, and Novartis, Speakers bureau: Pfizer, AbbVie, Amgen, UCB, BMS, Biogen, MSD, Novartis, Eli Lilly and Company, and Janssen pharmaceuticals, L. Dreyer: None declared

Background We have previously shown that the incidence rate of total knee replacements started to decrease among rheumatoid arthritis (RA) patients following the introduction of biological (b) DMARDs, but less is known on the impact of bDMARDs on the need for joint replacements (JR) of the upper limbs. Objectives To investigate the association between bDMARD introduction for the treatment of patients with RA on the trends of upper limb JR among newly diagnosed RA patients compared with a matched general population cohort (GPC) in Denmark. Methods Nationwide register-based interrupted time-series analysis using the Danish National Patient Register and Civil Registration System. Study populations: incident RA patients diagnosed at a rheumatology or general internal medicine clinic/department from 1996–2010. Intervention: introduction of bDMARDs in Denmark in 2002. Comparison: Each RA patient was matched on age, sex and municipality with up to 10 non-RA individuals (GPC). Outcome: Composite outcome of first shoulder, elbow, wrist, or finger replacement surgery (JR). Statistical analyses: 5 year age- and sex-standardised incidence rates of JR calculated for incident RA patients diagnosed biannually compared with GPCs. Outcome trends in the pre-bDMARD era (1996–2001) were compared with those in the bDMARD era (2003–2015) with a 1 year lag period in 2002. Results From 1996 to 2010, 26 458 incident RA patients were identified and compared with 257,505 GPCs (Table). The JR incidence rate was stable among RA patients in 1996–2001, but started to decrease from 2003 and onwards. Among GPCs, the incidence rate increased throughout the study period. Stepwise backward elimination to produce most parsimonious model: p-entry 0.2. * x per year based on biannual data. Abbreviations: pyrs, person years Conclusions Following the introduction of bDMARDs, the incidence rate of upper limb JR started to decrease among RA patients, whereas the incidence rate steadily increased from 1996–2015 among matched GPCs. The baseline incidence rate was 7-fold higher among RA patients than GPCs, but the absolute need for upper limb JR was low in both groups. Disclosure of Interest R. Cordtz: None declared, S. Hawley: None declared, D. Prieto-Alhambra Grant/research support from: Amgen, Servier, and UCB, Consultant for: UCB, Speakers bureau: Amgen, P. Hojgaard Speakers bureau: UCB and Celgene, K. Zobbe: None declared, A. Odgaard: None declared, S. Overgaard: None declared, L. E. Kristensen Speakers bureau: Pfizer, AbbVie, Amgen, UCB, BMS, Biogen, MSD, Novartis, Eli Lilly and Company, and Janssen Pharmaceuticals, L. Dreyer Speakers bureau: UCB and MSD

Background One in five patients are dissatisfied following knee arthroplasty and Purpose Are expectations regarding the impact of pain on life after knee arthroplasty predictive of one-year outcome? Does the impact of pain on preoperative quality of life (QOL) influence this relationship? Methods Longitudinal cohort study of 1044 uni-compartmental (43%) or total knee-arthroplasty (57%) (UKA or TKA) patients, aged mean 69±9 years. Preoperatively, patients reported the impact of pain on QOL and the expected impact of pain on life one-year post-arthroplasty (none, mild, moderate/severe/extreme). One-year postoperative outcomes: non-return to desired activity (specific activities were specified preoperatively), surgical dissatisfaction, not achieving Oxford Knee Score (OKS) minimal important change (MIC). Logistic regression including covariates was performed for all patients and subgroups (better vs. worse pre-operative pain-related QOL; UKA vs. TKA; osteoarthritis indication vs. other indication). Results Expecting moderate-to-extreme pain (vs. no pain) predicted non-return to activity (odds ratio (95% CI), 2.3(1.3, 4.1)), dissatisfaction (4.0(1.7, 9.3)), and not achieving OKS MIC (3.1(1.5, 6.3)). Expecting mild pain (vs. no pain) predicted worse outcomes for patients with better preoperative pain-related QOL (non-return to activity: 2.7(1.5, 4.8), not achieving OKS MIC: 2.5(1.1, 5.5)). Expecting moderate-to-extreme pain (vs. no pain) predicted worse outcomes for patients with worse preoperative pain-related QOL (non-return to activity: 2.4(1.1, 5.5), dissatisfaction: 5.0(1.7, 14.8), not achieving OKS MIC: 3.4(1.4, 8.6)). The odds of a poor outcome in people with worse expectations was higher for UKA patients. Conclusions Expecting a worse outcome predicted surgical dissatisfaction, less clinical improvement and non-return to desired activity. Patients expecting a more optimistic outcome relative to preoperative status achieved better surgical outcomes.

Introduction: Rheumatoid arthritis is a systemic inflammatory disease, and classical disease-modifying antirheumatic drugs (cDMARDs) have proven efficacy. It is unknown what impact cDMARDs might have on dementia as an outcome.Methods: Incident diagnoses of rheumatoid arthritis in persons over 18 years from 1995 to 2011 were identified from the UK Clinical Practice Research Datalink. There were 3876 cDMARD users and were propensity score matched to 1938 nonusers, on a wide range of confounders. Impact on dementia was assessed using survival models.Results: cDMARD users were at reduced risk of dementia (hazard ratio: 0.60; 95% confidence interval: 0.42-0.85). The effect was strongest in methotrexate users (hazard ratio: 0.52; 95% confidence interval; 0.34-0.82).Discussion: The strong effect of cDMARD use on halving of dementia risk requires replication in a trial and may provide an important therapeutic pharmacological treatment.

Background Falls are the leading injury type in elderly populations and a major health burden and cause of death globally. Most of such burden is due to bone fractures. In the Global Burden of Diseases (GBD) Initiative, the attributable burden of falls due to low bone mineral density (BMD) was analysed through its relationship with fractures. Objectives To measure the percentage of disability-adjusted life years (DALYs), years lived with disability (YLDs) and deaths due to falls attributable to low BMD in European population for the year 2015. Methods The estimates followed the Counterfactual Risk Assessment Methodology used in the GBD study (1). Systematic review was performed seeking population-based studies with femoral neck (FNBMD) measured by Dual-X-Ray-Absorptiometry in people 50 years and over. Age- and sex- specific levels of mean +/-SD FNBMD (g/cm2) were extracted from eligible studies, and this was used as the exposure variable. The age and sex-specific 99th percentile from non-Hispanic whites in the National Health and Nutrition Examination Survey (NHANES) 2009–2010 was used as theoretical minimum risk factor exposure distribution, to estimate the potential impact fraction (PIF) of FNBMD for fractures. Relative risks of FNBMD for fractures were obtained from a previous meta-analysis (2). Coded hospital data was used to calculate the fraction of falls-related deaths due to fractures. Disability levels were established by applying disability weights to each type of fracture. Then, PIFs were applied to obtain attributable deaths and disability due to low BMD. Results The percentage of falls-related preventable deaths attributable to low BMD is around 9% in the 50–54 age group, increasing to 84% in those aged 80 years and over. Total health burden (DALYs) and disability attribution (YLDs) also increase with age, from 19% and 25% in 50–54 years old, respectively, to 61% and 44% and population aged 80 years and above, respectively. Low BMD constitutes the most important preventable risk factors for falls-related DALYs from 50 years and above, followed by alcohol, occupational risk and smoking. Conclusions Low BMD is a major preventable risk factor that explains a very remarkable proportion of falls health burden in Europe, in particular in those aged 70 years and above. This is a growing concern, given the population trajectories, and requires urgent attention. References Forouzanfar M et al, Lancet 2016. , Johnell O et al, JBMR 2015. Disclosure of Interest None declared

Summary Objectives: The RANK/RANKL/OPG system is involved in the determination of bone mineral density (BMD) and bone microarchitecture. Our study seeks to evaluate if there are SNPs in the 3'UTR region of the RANK gene associated with osteoporotic phenotypes. Material and methods: Seven genetic variants in 1,098 women from the BARCOS cohort were genotyped, and their association with BMD and osteoporotic fractures evaluated. An interaction with SNP rs9594738 in the RANKL gene which was previously associated with BMD was tested. Results: None of the SNPs were associated significantly with BMD. SNP rs78326403 was associated with wrist/forearm fractures (Log-additive model odds ratio (OR)=3.12 [IC 95%: 1.69 ; 5.75]; p=7.16x10 -4 ), while SNP rs884205 was associated with fractures of the spinal column (OR=4.05 Recessive; [95% CI: 1.59 ; 10.35]; p=8.24x10 -3 ). Lastly, an interaction was detected between SNP rs9594738 from RANKL and rs78326403 from RANK on the presence of fracture (p=0.039). The analysis of the effects of combined genotypes rs9594738 and rs78326403 pointed to an increase in the prevalence of fractures in subjects with a greater number of unfavourable alleles, the ORs being 2.76 [95% CI: 1.30 ; 5.81]; p=0.007) and 5.14 [95% CI: 1.37 ; 15.67]; p=0.007) for 2 and ≥3 unfavourable alleles respectively, in comparison with none/1. Conclusions: Two SNPs in 3'UTR from the RANK gene predispose to site-dependent osteoporotic fracture. An interaction with SNP rs9594738 from RANKL suggests an additive effect of BMD and bone strength.

s / Osteoarthritis and Cartilage 21 (2013) S63–S312 S155 291 PREDICTORS OF POOR OUTCOME (HIGH USE OF NON-STEROIDAL ANTI-INFLAMMATORY DRUGS) AT YEAR 1 FOLLOWING TOTAL KNEE/HIP ARTHROPLASTY: THE PRESS-UP COHORT STUDY D. Prieto-Alhambra y,z, A. Judge y,z, M. Javaid y,z, F. Palliso x, M. Espallargues k, C. Cooper y,{, N. Arden y,{. yBotnar Res. Ctr., Univ. of Oxford, Oxford, United Kingdom; z Lifecourse Epidemiology Unit, Univ. of Southampton, Southampton, United Kingdom; x Traumatology and Orthopaedics Dept., Santa Maria Hosp., Lleida, Spain; kCatalan Joint Registry, Catalan Agency for Hlth.Information, Assessment and Quality (AIAQS), Gen.itat de Catalunya, Barcelona, Spain; {MRC Lifecourse Epidemiology Unit, Univ. of Southampton, Southampton, United Kingdom Purpose: Implant survival is the most accepted measurement of total knee (TKA) or hip arthroplasty (THA) results. There is a need for shortterm surrogates for revision for both research andmonitoring purposes. We have shown that highest utilisation of non-steroidal anti-inflammatory drugs (NSAIDs) in the first year following surgery is related to increased revision risk, and hence a useful surrogate for “poor outcome”. We therefore aimed to identify predictors of high NSAID use at year 1 after TKA and THA surgery. Methods: Study design and population: We used data from the Catalan Joint Registry (RACAT), and linked it (85% linked) to computerized primary care records and pharmacy invoice data (SIDIAP Database). We identified patients aged >1⁄440 years undergoing primary TKA/THA for osteoarthritis registered in the resulting dataset in the period 1/1/2005-31/07/2012). We excluded patients receiving revision surgery in the first year post-surgery. Ă Outcome assessment: NSAID utilisation was measured using pharmacy invoice data, and quantified in number of Daily Defined Doses (DDDs) according to the WHO ATC/DDD index. We classified patients in the top quintile (percentile 80 and over) of utilisation as those with a “poor outcome”. Potential predictors: we defined a priori a set of predictors of poor outcome based on previous knowledge and biological plausibility, including: age, sex, socio-economic status, Charlson co-morbidity index, alcohol drinking, smoking status, body mass index, stroke/TIA, ischaemic heart disease, peripheral artheriopathy, depression/anxiety disorders, type 2 diabetes mellitus, previous fracture, chronic kidney failure, COPD, use of atypical analgesics (gabapentin, pregabalin or trycyclic antidepressants) in the previous year, use of NSAIDs in the previous year. Analysis: Backwards stepwise logistic regression (p-entry 0.05, p-exit 0.1) models were fitted to identify predictors of good outcome (as defined above). Results: 22,221 and 10,173 patients undergoing TKA and THA for osteoarthritis were included. Female sex, lower socio-economic status, obesity, previous use of atypical analgesics, and amount of NSAIDs used in the year prior to surgery were associated with “poor outcome” in both THA and TKA patients [Figure, top and bottom respectively]. Conversely, Charlson co-morbidity index had an effect on poorer outcome for TKA patients, and a history of depression/ anxiety disorders was related to poorer outcome following THA, but had no significant effect on the other subpopulation. Conclusions: We report for the first time on a set of predictors of “poor outcome” as defined on the basis of NSAID usage during the first year following TKA surgery. A predictive tool can be built using these in order to target patients who would benefit the least from this surgical procedure. A validated version of such tool would be of interest for patients, clinicians and health-care managers. 292 BISPHOSPHONATE USE AND IMPROVED IMPLANT SURVIVAL: A NATION-WIDE COHORT STUDY D. Prieto-Alhambra y,z, A. Lalmohamed x, B. Abrahamsen {,k, N. Arden y,z, A. de Boer x, P. Vestergaard , F. de Vries z,yy. yBotnar Res. Ctr., Univ. of Oxford, Oxford, United Kingdom; zMRC Lifecourse Epidemiology Unit, Univ. of Southampton, Southampton, United Kingdom; xDiv. of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Inst. for Pharmaceutical Sci., Utrecht Univ., Utrecht, The Netherlands; kDept. of Med. F, Gentofte Hosp., Hillerod, Denmark; {OPEN, Inst. of Clinical Res., Univ. of Southern Denmark, Odense, Denmark; Aalborg Hosp., Aalborg Univ., Aalborg, Denmark; yyDiv. of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Inst. for Pharmaceutical Sci., Utrecht Univ., Utrecht, Utrecht, The Netherlands Purpose: Osteolysis and aseptic loosening are the most common cause of revision arthroplasty worldwide. Bisphosphonates might improve implant survival through their anti-osteoclast effects. We aimed to study the association between bisphosphonate use and implant survival. Methods: A retrospective cohort study was conducted within the Danish nationwide registries (5.5 million residents). We identified patients aged >1⁄440 years undergoing total joint replacement (TJR) during the study period (1998-2007) using ICD10 codes. Patients with inflammatory arthritides, bone Paget, hip fracture and use of DMARDs were excluded. Each participant was followed up until end of study, date of emigration, revision surgery, or patient's death, whichever came first. Participants were classified as bisphosphonate users (BPU) if they had been on treatment for at least 6 months. A time-varying exposure was used to avoid immortal-time bias. Up to six BP non-users (BPNU) undergoing arthroplasty were matched to each BPU using propensity scores. Stratified Cox regression was used to model implant survival according to bisphosphonate use. Further, we studied the association between duration of use, adherence (medication possession ratio1⁄4MPR), and timing of therapy initiation (pre-op vs post-op) and implant survival. Finally, we tested for a-priori defined interactions

s / Osteoarthritis and Cartilage 22 (2014) S57–S489 S214 and regional JRRs) members of the ISAR with publicly available annual reports in English. We compared definitions and reporting of common outcomes: mean age of patients; primary and revision procedures specific to total hip arthroplasty (THA) and hip resurfacing arthroplasty (HRA); definitions, coding, analysis, and reporting of revisions; documentation of reasons for revision; and the type, frequency, and reporting of PROMs. Results: Eight of 24 identified hip JRRs met our inclusion criteria: the Australian Orthopaedic Association National Joint Replacement Registry, the Canadian Joint Replacement Registry, the National Joint Registry of England and Wales, the New Zealand Joint Registry, the Norwegian Arthroplasty Register, the Scottish Arthroplasty Project, the Slovak Arthroplasty Register, and the Swedish Hip Arthroplasty Register. The annual number of primary and revision hip replacement procedures was reported by all JRRs. Six JRRs reported the annual number of primary procedures specific to HRAs, while just four JRRs reported the number of revision HRAs. Seven JRRs reported the mean age of THA patients, and two JRRs reported the mean age of HRA patients. The definition of revision was similar across all JRRs. Various units (hips, patients and components) and metrics (revision burden, person-time incidence rates and cumulative percent revised) were used to analyze and report revisions. Kaplan-Meier survival analysis was used among six JRRs that provided survivorship curves. Seven JRRs reported reasons for revision for all types of hip replacements, while only two JRRs provided reasons for revision for HRAs. Although three JRRs described the collection of PROMs, only one JRR reported PROMs (EQ-5D, pain and satisfaction visual analogue scales) in their annual report. Conclusions: Our review highlights considerable variability in the collection, analysis, and reporting of surgical and patient-reported outcomes among eight hip JRRs, which creates challenges when comparing outcomes across JRRs. Few JRRs currently collect and report PROMs, despite increased pressure among policy makers to use PROMs to assess appropriateness of care. Going forward, JRRs have the opportunity to collectively incorporate standardized PROMs into regular data collection and encourage their widespread use, though the choice of instrument and frequency of data collection, analysis, and reporting will require careful consideration. The integration of PROMs along with standardizedmetrics and analysis methods has the potential to improve the monitoring and comparability of joint replacement outcomes internationally, and ultimately improve care provided to patients requiring joint replacement surgery. 375 OUTCOMES AFTER TOTAL HIP REPLACEMENT R. Pinedo-Villanueva yz, D. Turner x, J.P. Raftery k, C. Cooper z, N.K. Arden y. yUniv. of Oxford, Oxford, United Kingdom; zMRC Lifecourse Epidemiology Unit, Southampton, United Kingdom; xUniv. of East Anglia, Norwich, United Kingdom; kUniv. of Southampton, Southampton, United

Background Patients with osteoarthritis (OA) use different drugs in search for relief, with potential impact on both safety and costs. There is a scarcity of data on drug utilization in these patients. Objectives We used a large database including primary care medical records and pharmacy invoice data to explore use of the following drugs in OA patients in the period 2006-2010: non-steroidal anti-inflammatory drugs (NSAIDs), Symptomatic Slow Acting Drugs for OA (SYSADOA), COX-2 inhibitors (COX2i), opioids, and other analgesics (paracetamol and metamizol). Methods SIDIAP contains anonymised clinical information from primary care records and pharmacy invoice data for a representative >5 million people in Catalonia (North-East Spain). We screened this database (www.sidiap.org) to identify those aged 40 years or older with a new diagnosis of OA using ICD-10 codes. Among these, we ascertained prevalence of use of oral NSAIDs, COX2i, SYSADOA, opioids, and analgesics (all alone and in combination) in the period 2006-2011. We estimated prevalence (and 99% Confidence Intervals) of use of these drugs and their combinations, and the proportion of occasional (MPR≥25%) and regular (MPR≥50%) users for each of them. Results We identified 281,356 patients with an incident clinical diagnosis of OA. Among these, 128,314(45.6%) were treated with 3 or more drugs, and 57,835(20.6%) with none of the drugs studied. The 3 most common combinations of two drugs were: oral NSAID+analgesic (12.2%); 2.topical NSAID+analgesic (2.5%); and oral NSAID+SYSADOA (1.8%). Besides, 34,672(12.3%) patients received only 1 drug, the 3 most common being, in descending order: oral NSAID, analgesics, and SYSADOA. The proportions of occasional and regular users were highest for SYSADOA (24.5% occasional and 6.9% regular users), and lowest for opioids (7.3% occasional and 1.9% regular users). Conclusions About 75% of OA patients are treated with at least 2 drugs, and above half of them with 3 or more. However, compliance with these drugs is very low, and hence both clinical benefits and safety issues are difficult to predict using data from clinical trials, where compliance is high. These data are of interest for health care provision and clinical management of patients with OA. Disclosure of Interest D. Prieto-Alhambra Grant/research support from: Unrestricted grant from BIOIBERICA SA, N. Wilson: None Declared