bluuebunny/crossref_metadata_2025_split huggingface dataset:
P246 Predicting non-response to biologic therapy amongst patients with axSpA: results from the British Society for Rheumatology Biologics Register
Authors: Dean Linda E , Pathan Ejaz , Jones Gareth T , Macfarlane Gary J 
Published: April 2020

Abstract

Background
Biologic therapies have transformed treatment for axial spondyloarthritis (axSpA). However, although studies report overall benefits, these are average effects. There remains a subset of patients in whom response is not achieved. Here, we aimed to identify characteristics of patients who may need additional therapeutic approaches to optimise outcome.

Methods
The British Society for Rheumatology Biologics Register for Ankylosing Spondylitis (BSRBR-AS) is a prospective cohort of axSpA patients recruited from 83 centres across Great Britain. All patients were biologic-naïve at recruitment, however those in the “biologic” cohort commenced a biologic therapy shortly thereafter, or during follow-up. Clinical data was collected from medical records, and socio-economic/patient reported outcomes via questionnaires. Response was assessed at first follow-up, between 10 weeks and 9 months from therapy commencement, and defined in four ways: ASAS20 and ASAS40 criteria, ≥1.1 reduction in ASDAS, and achieving moderate/inactive ASDAS (&lt;2.1). Factors associated with non-response were assessed by logistic regression and parsimonious models identified using stepwise methods. The ability to predict non-response was assessed by positive predictive value (PPV).

Results
335 biologic participants provided information at a median follow-up of 14 weeks (inter-quartile range (IQR) 12-17). Median age was 47 years (IQR 36-56), 69% were male and 61% met AS modified New York criteria. The proportion meeting response varied by criteria: ASAS20 52%, ASAS40 33%, ASDAS reduction 47% and ASDAS &lt;2.1 35%. Socio-economic circumstances predicted non-response, specifically (in all models) work status and (in some models) fewer years of education (Table 1). Poorer mental health and high number of co-morbidities was associated with non-response across multiple (but not all) outcomes, while body mass index, enthesitis and gender were included in models for a single outcome. Disease-specific factors were largely not associated with non-response. All models demonstrated a good level of fit and were effective at predicting non-response (PPV 65%-77%).

Conclusion
We have identified factors which predict non-response to biologic therapy, some of which may be modifiable and others which identify patients who are unlikely to benefit from biologic therapy alone. In such patients additional/alternative treatment strategies should be considered to maximise the benefits which others gain from biologic therapy.

Disclosures
L.E. Dean None. E. Pathan Other; E.P. has recieved salary funding from Jansen (2019) and Merck (2018). G.T. Jones None. G.J. Macfarlane None.
P251 Pattern of mortality for patients with axSpA: a retrospective UK database analysis
Authors: Morgan Christopher L. I , White Abigail , Tomlinson Mark , Scott Amie , Tian Haijun 
Published: April 2020

Abstract

Background
This study characterises mortality for patients with axial spondyloarthritis (axSpA) and compares mortality rates with a matched, non-axSpA population.

Methods
The Clinical Practice Research Datalink, a large routine primary care database in the UK, was used to conduct this study. Patients with an incident diagnosis of axSpA from 2003-2017 were identified and matched to non-axSpA patients according to age, sex, primary care practice and concurrent practice registration. The date of first axSpA diagnosis defined the index date, and patients were followed up until death or censored at the end of follow up. Crude mortality rates were calculated and time to death from index date was analysed using the Kaplan-Meier estimator. For patients from primary care practices linked to the Office of National Statistics (ONS), cause-specific unadjusted rate ratios are presented. Two adjusted Cox proportional hazard models were conducted: 1) to assess relative mortality between axSpA patients and non-axSpA controls; and 2) to assess disease-specific factors associated with mortality for the axSpA population only. Only patients whose record could be potentially linked to ONS mortality data were included in the cause of death analysis.

Results
4,136 incident axSpA cases were identified and matched to non-axSpA controls. Crude mortality rates were 18.9 and 11.5 per 1,000 patient-years, respectively. The most common causes of death in the axSpA cohort were coronary heart disease, cerebrovascular disease and malignant neoplasm of the bronchus and lung (Table 1). For all-cause mortality, there was a significantly increased hazard ratio (HR) of 1.531 (95% confidence interval [CI] 1.291-1.816; P &lt; 0.001) for axSpA vs non-axSpA patients. Age (HR 1.083 [95% CI: 1.074-1.093]; P &lt; 0.001), history of infection (HR 1.358 [95% CI: 1.082-1.705]; P = 0.008), Charlson Comorbidity Index (HR 1.194 [95% CI: 1.137-1.253]; P &lt; 0.001) and current smoker status (HR 1.853 [95% CI: 1.396-2.461]; P &lt; 0.001) were all significantly associated with time to death.

Conclusion
In this study, we have shown that the presence of axSpA is associated with increased mortality compared with controls. Prior infection, comorbidity and current smoker status were associated with the greatest increased risk of mortality in patients with axSpA.

Disclosures
C.L.I. Morgan: Other; Employee of: Pharmatelligence. A. White: Shareholder/stock ownership; Novartis. Other; Employee of: Novartis. M. Tomlinson: Consultancies; Novartis. A. Scott: Consultancies; Novartis. H. Tian: Other; Employee of: Novartis.
P256 Reproductive health outcomes in women with PsA
Authors: Murray Kieran , Moore Louise , Young Francis , McAulliffe Fionnuala , Veale Douglas J 
Published: April 2020

Abstract

Background
There is quality data showing rheumatoid arthritis (RA) improves in pregnancy and flares postpartum and that active disease is associated with adverse foetal outcomes. For psoriatic arthritis (PsA), the data is less clear, with previous studies giving contrasting results. We prospectively monitored disease control, maternal and foetal outcomes in women with PsA attending our multidisciplinary service.

Methods
Age, medications, disease control, maternal and foetal outcomes were reviewed and descripitive statistics applied.

Results
14 patients were reviewed. 12 became pregnant. There were 20 pregnancies in total. Eight patients had 1 pregnancy. Two patients had 3 pregnancies, 1 patient was pregnant twice and 1 patient had 4 pregnancies and is currently pregnant. Two patients failed to become pregnant.
There were 13 live births (one set of twins), 7 vaginal deliveries and 5 Caesarean sections. There were 6 intrauterine deaths (4 1st trimester, 2 2nd trimester). Two patients had postpartum complications (grade 4 vaginal tear and Caesarean wound infection). Mean foetal birth weight was 3.54kg (national average 3.49kg). 8 infants (55%) were breastfeeding at 6 weeks (national average 62%). 14 patients were on a DMARD (including oral steroids) in pregnancy. There were 8 pregnancies on a bDMARD alone, one on a bDMARD plus prednisolone. The bDMARDs used were certolizumab (five times), adalimumab (twice), infliximab (once) and etanercept (once). Two patients were on prednisolone alone. One patient on sulfasalazine plus prednisolone. One pregnancy on sulfasalazine plus hydroxychloroquine, 1 on sulfasalazine alone. Two patients were on NSAIDs. Disease activity was measured using DAS28-CRP 3 as this is validated for use in RA during pregnancy. Overall, the mean disease activity scores decreased during pregnancy and increased postpartum. After applying the European League Against Rheumatism-defined response criteria disease activity, almost half of the women had at least a moderate response during pregnancy and more than one-third had at least a moderate flare post partum, particularly at 6 weeks. The postpartum flare may be underestimated as medication use was remarkably increased after delivery. At 6 weeks, in five cases the bDMARD therapies had already been restarted. In two cases, the patients missed this appointment. One patient was started on methotrexate at their 6-week review.

Conclusion
Disease activity generally improved during pregnancy and flared postpartum. Miscarriage rates were higher than the general population (32% v 20%). Birth weights and breastfeeding rates at six weeks were similar.

Disclosures
K. Murray None. L. Moore None. F. Young None. F. McAulliffe None. D. Veale None.
P258 Real-world secukinumab retention, response rates and adverse events in the treatment of PsA and axSpA
Authors: Tindell Alistair , Batool Saira , McGucken Andrew , Siebert Stefan 
Published: April 2020

Abstract

Background
Secukinumab, an IL-17A inhibitor, has been licensed for use in the United Kingdom for both axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) for several years. Despite this there is minimal published data on its use out with randomised controlled trials. We present here the collated real-world rheumatology experience of secukinumab use in Glasgow.

Methods
Patients who have ever received secukinumab for any rheumatology indication were identified using available medical records (from 14/05/2012 to 18/09/2019). Diagnosis, baseline demographics, disease activity at baseline and at 6 months, and whether patients are still currently on secukinumab was recorded. Primary inefficacy was defined as stopping treatment due to inefficacy ≤6 months. Reasons for discontinuation were also recorded. As disease activity scores were variably recorded, the primary outcome was retention rate as a surrogate for efficacy and lack of adverse event. Patients only included in disease scores if scores available both at baseline and 6 months.

Results
352 patients (with 530 patient-years of exposure) identified. 251 (71.3%) patients currently remain on secukinumab. 301 of 336 (89.6%) patients remained on drug at six-month review (16 await review). Characteristics and response of two main diagnostic groups listed in Table 1 (Note: 3 patients had SAPHO, 5 had Juvenile Idiopathic Arthritis, 1 had reactive arthritis). Common adverse events were infections (11 patients), rash and/or pruritis (6 patients), mood change and/or fatigue (4 patients). Three patients developed inflammatory bowel disease (IBD) subsequent to starting secukinumab. Five patients had pre-existing IBD, none of which flared on secukinumab. Two patients required hospitalisation for abscesses whilst on secukinumab. One patient had a stroke and one patient had a myocardial infarction whilst on secukinumab - both patients had multiple risk factors for cardiovascular disease. No malignancies identified. Three patients died, with none felt related to secukinumab (cerebellar haemorrhage in warfarinised patient with high INR; pneumonia six months after switching from secukinumab to tocilizumab; one out of hospital death over one year after stopping secukinumab).

Conclusion
In this real world cohort of patients with axSpA and PsA, secukinumab retention rates at 6 months are high with no new safety signals identified.

Disclosures
A. Tindell None. S. Batool None. A. McGucken None. S. Siebert Consultancies; S.S. has received speaker or consultation fees or honoraria from AbbVie, UCB, Janssen, Boehringer Ingelheim, Novartis, Celgene. Honoraria: S.S. has received speaker or consultation fees or honoraria from AbbVie, UCB, Janssen, Boehringer Ingelheim, Novartis, Celgene. Grants/research support; S.S has received funding for research/ grants from Pfizer, Janssen, BMS, Celgene, UCB, Boehringer Ingelheim, Novartis, GSK.
P272 How well are conventional DMARDs tolerated in PsA: a real-world study
Authors: Jawad Issrah , Nisar Muhammad K 
Published: April 2020

Abstract

Background
NICE guidelines recommend the first line use of DMARDs in psoriatic arthritis (PsA). However, studies show that many conventional treatments like methotrexate are poorly tolerated. There is hitherto no published real-world data addressing the tolerability of DMARDs in PsA. Our objective was therefore to assess the drug management in PsA with focus on tolerability and the reasons for therapy cessation.

Methods
We conducted a retrospective analysis of all PsA patients enrolled in electronic database up to April 2019 at our university teaching hospital. We had access to full patient records including details on co-morbidities, drugs and disease management.

Results
335 patients were identified with a formal diagnosis of PsA. Mean age of the cohort was 46 years (13-81) and 58% were female. 9% of the individuals had diabetes and 18% had concurrent cardiovascular disease. 1/10th reported to be current smokers and 8% had a diagnosis of depression. 48% of the group had clinically active disease. Same percentage were taking a single DMARD. 10% had trialled 3 or more drugs. 62% of patients had discontinued one or more DMARDs prior. The mean duration before discontinuing a DMARD was 9.9 months. Methotrexate was the best tolerated and on average discontinued after 13.4 months (range: 4 days to 10.9 years). Sulfasalazine and hydroxychloroquine were discontinued after an average of 8.4 (11 days to 4.27 years) and 12.5 months (1.3 months to 2.88 years) respectively. Leflunomide was the least tolerated DMARD and stopped after an average of 5.5 months (7 days to 2.53 years). The main reason for stopping a medication was gastro-intestinal symptoms which accounted for 42% of all the reported side effects. This applied to both methotrexate (43%) and sulfasalazine (46%) discontinuation. The leading reasons for discontinuing hydroxychloroquine were jointly GI symptoms and other side effects at 43% each. Leflunomide was stopped in 50% of cases due to neurological symptoms.

Conclusion
To our knowledge, this is the first report confirming poor retention rate of oral DMARDs in a real world PsA cohort managed over 20 years. In the context of chronic disease, the median duration of treatment is short. Our analysis did not include patients who suffer from side effects but continue therapy thereby impacting treatment adherence and hence the true scale of the issue is likely higher. Though NICE guidelines stipulate the need of an adequate trial of minimum two DMARDs prior to therapy escalation, these drugs are not well tolerated and thus pose a challenge to clinicians. One potential solution is earlier adoption of biological therapies, which are increasingly cost effective and have been shown to be better tolerated.

Disclosures
I. Jawad None. M.K. Nisar None.
P280 Clinical burden of concomitant joint disease in psoriasis: a US-linked claims and electronic medical records database analysis
Authors: Tillett William , Skornicki Michelle , Prince Patricia , Suruki Robert , Lee Edward , Louder Anthony 
Published: April 2020

Abstract

Background
Psoriasis (PSO) is an inflammatory skin condition, impacting physical and psychological well-being. PSO patients may develop psoriatic arthritis (PsA), a painful joint disease that further impacts quality of life. The objective was to examine rates of metabolic disease and depression in patients with PSO and PsA.

Methods
Claims data linked to electronic medical records were examined (Jan-2007-Mar-2018). Prevalent PSO patients were followed until end of data collection and categorized based on development of PsA (PSO+PsA cohort; defined by ICD9/10 codes in patients without PsA at baseline). Follow-up rates of comorbidities, including metabolic disease and depression, were compared for those with/without PsA, presented as cases per 1,000 patient-years (1000PY).

Results
Progression to PsA occurred in 2,311 (12%) patients. Follow-up rates of hyperlipidemia, hypertension, diabetes, and cardiovascular disease in the PSO+PsA cohort were 1.4-times (326 vs 234/1000PY), 1.6-times (357 vs 228/1000PY), 1.7-times (119 vs 72/1000PY), and 1.4-times (71 vs 50/1000PY) that observed in the PSO-only cohort, respectively. In patients without baseline metabolic disease, higher rates in PSO+PsA vs PSO-only remained (approximately 1.5-times and 1.3-times higher rates of hypertension and hyperlipidemia, respectively). The rate of depression was 140 vs 92/1000PY in the PSO+PsA vs PSO-only cohort; when examined in patients without baseline depression, rates were about half that observed in the overall population (72 vs 49/1000PY).

Conclusion
PSO+PsA patients had a substantial clinical burden, characterized by 40-70% higher rates of metabolic disease and depression than for patients who did not progress to PsA.

Disclosures
W. Tillett: Consultancies; AbbVie, Celgene, Janssen, Lilly, Novartis, Pfizer and UCB Pharma. Grants/research support; AbbVie, Celgene and Lilly. M. Skornicki: Other; Employee of Aetion. P. Prince: Other; Employee of Aetion. R. Suruki: Other; Employee of UCB Pharma. E. Lee: Other; Employee of UCB Pharma. A. Louder: Other; Employee of Aetion.
P282 Outcome for PsA biologic switchers following primary inefficacy of TNFi therapy in a secondary care cohort: sequential TNFi versus switching mode of action
Authors: Naja Meena , Santos Liliana R , Shipa Muhammad , Mandy Greenwood , Castelino Madhura 
Published: April 2020

Abstract

Background
TNFi are the most used first line of biologic disease modifying anti-rheumatic drugs (bDMARDs) in PsA. In primary loss of response (PLR) to TNFi, there is no current evidence that directs the choice of second line bDMARDs. Our aim in this work was to compare drug survival for those who switched to a second TNFi versus alternative agents in real life.

Methods
Data was analysed retrospectively from a cohort of 400 PsA patients followed through from 2002-2019. Statistical analysis was carried out with descriptive statistics and t-test analysis using SPSS version 22.

Results
Out of 400 patients, 220 (55.0%) were started on bDMARD treatment. Of these 220, 212 (96.5%) were started on TNFi as initial therapy. PLR was seen in 42 of these patients (19.8%). The median drug survival of initial TNFi therapy was 7.1 months (interquartile range [IQR] 3.6 - 53.4 months). Of the 42 patients with PLR: 32 (76.2%) were switched to a second TNFi; 6 (14.3%) were switched to ustekinumab and 4 (9.5%) were switched to secukinumab. 21 of the 32 patients switched to a second TNFi were subsequently switched onto a third biologic due to treatment failure (65.6%). The median drug survival of the second TNFi in this group was 7.7 months (IQR 3.0 - 26.3 months). 3 out of the 6 (50%) patients who were switched to ustekinumab were then subsequently switched, this was due to primary inefficacy in 66.7% and adverse events in 33.3%. The median drug survival of ustekinumab in this group was 10.0 months (IQR 0.0 - 16.0 months). All 4 patients switched to secukinumab continue on this treatment with no drop outs, giving a median drug survival 12.3 months (IQR 6.5 - 19.5 months).

Conclusion
Our data suggests that patients with PLR to TNFi in PsA who switched mode of action to IL-17 inhibitor appeared to have better drug survival than subsequent TNFi or IL-12/23 inhibitors. Exploring the clinical biomarkers for those with successful switch to non-TNFi bDMARD in a larger cohort would help with targeting the most appropriate individuals and early disease control.

Disclosures
M. Naja None. L. R. Santos None. M. Shipa None. G. Mandy None. M. Castelino None.
Fraud exception to privilege: Addlesee & Ors v Dentons Europe LLP [2020] EWHC 238 (Ch)
Authors: Munby Thomas 
Published: April 2020

Abstract
Some months after Addlesee & Ors v Dentons Europe LLP produced an important judgment of the Court of Appeal in relation to the statue of legal professional privilege following the dissolution of a corporate client,1 the same litigation has given rise to a judgment addressing another area of the law of privilege.
Determination of plasma-chlortetracycline (CTC) concentrations in grazing beef cattle fed one of four FDA approved free-choice CTC-medicated minerals
Authors: Reppert Emily J , Reif Kathryn E , Montgomery Shawnee R , Magnin Geraldine , Zhang Yuntao , Martin-Jimenez Tomas , Olson K C , Coetzee Johann F 
Published: April 2020

Abstract
Control of active bovine anaplasmosis in the United States is predicated on the use of chlortetracycline (CTC)-medicated feed throughout the vector season. However, data describing population pharmacokinetics of chlortetracycline in cows, on pasture, having free-choice access to CTC-medicated mineral for consecutive months is lacking. This study documented plasma-CTC concentrations in grazing cows during peak vector season in an anaplasmosis endemic herd. Each pasture was administered one of the four Food and Drug Administration approved CTC-medicated mineral formulations and were assigned as follows: 0.77 g/kg, Aureo Anaplaz C700 Pressed (Sweetlix Livestock Supplements, Mankato, MN); 5.5 g/kg, Purina Anaplasmosis Block (Purina Animal Nutrition, Gray Summit, MO); 6.6 g/kg, Stockmaster Aureo FC C6000 Mineral (Hubbard Feeds, Mankato, MN); 8.8 g/kg, MoorMan’s Special Range Minerals AU 168XFE (ADM Animal Nutrition, Quincy, IL). Blood samples were collected monthly for determining plasma drug concentration by Ultra performance liquid chromatography (UPLC) and mass spectrometry. Continued plasma-CTC monitoring allowed for characterization of trends between treatment groups (pastures), age groups (&lt;3 yr or &gt;4 yr), and sampling times (June to October). Results indicate formulation (pasture) and time were significant factors affecting concentrations of CTC in plasma. Cows exposed to 5.5 g/kg block formulation recorded higher CTC plasma concentrations compared with other pasture groups (P = 0.037). Plasma-CTC concentrations increased over time (month of measurement; P = 0.0005). Specifically, concentrations measured after 5 months of continuous CTC treatment were higher than those measured in earlier months.
Collagen VI (CVI) antibodies regulate macrophages differentiation through FcgammaRIIb signal transduction pathway
Authors: Li Zhonghao , Zhao Ming 
Published: April 2020

We previously reported that monoclonal antibody against collagen VI (CVI mAb) regressing atherosclerotic plaque through inducing the shift of macrophage differentiation, namely from M1 to M2, and ensuing the macrophages engulf the plaque lipids and transfer the lipids to HDL through restoring lipid transfer protein ABCA1 expression. Here we report the cellular signal transduction on the CVI mAb inhibition of oxLDL‐induced M1 differentiation. Using purified human CD14+ cells, we find that oxLDL induces M1 differentiation is JNK and ERK MAPKs dependent. And CVI mAb inhibits M1, while activates M2 differentiation, though oxLDL also activates M2 differentiation in some way, but the M1/M2 ratio are significantly reversed by CVI mAb. The molecular mechanism behind these is that CVI mAb activates macrophage FcgammaRIIb and its downstream SHIP and Dok phosphatases, and inhibits Syk and Ras signal transduction pathway, which are MAPKs upstream kinases, so that CVI mAb inhibits ERK, JNK, and p38 MAPKs activation, and ensuing M1 differentiation. Thus, we found the signal transduction pathway of CVI mAb inhibition of oxLDL‐induced M1 differentiation: CVI mAb→FcgammaRIIb→SHIP→Dok→Syk and Ras→ERK and JNK MAPKs→M1. These results might give a new clue on control the lipids‐induced inflammatory reaction on the large blood vessel and therapeutic method to prevent atherosclerosis.Support or Funding InformationThis work was supported by the National Natural Science Foundation of China (grants 81772074, 81974045), the Natural Science Foundation of Guangdong, China (grant 2012B050600002), the Guangdong Province Talent Recruitment Foundation and the Guangdong Innovative Research Team Program (No. 201001Y0104675344), Project of Guangzhou city scientific plan (201804020002).