bluuebunny/crossref_metadata_2025_split huggingface dataset:
EP19 Hyperferritinaemia causes in a UK district general hospital
Authors: Fieldman Tom , Stimson Laura , Zeb Shabeena , Alderson Steven , Lloyd Mark 
Published: April 2020

Abstract

Background
Hyperferritinaemia has multiple causes including iron overload, liver disease, and systemic inflammation either in the context of infection, autoimmunity, or malignancy. Marked hyperferritinaemia has been used to aid diagnosis of rare autoimmune conditions such as adult onset Still’s disease.

Methods
Patients with plasma ferritin concentrations over 3000 μg/L from 7 April 2014 until 30 August 2019 (just over 5 years) in a district general hospital were identified. Those without sufficient documentation to identify the likely causes of hyperferritinaemia were excluded. Included patients (n = 283) were grouped according to maximum ferritin concentration, and likely causes of hyperferritinaemia from the following list were classified as follows: Infection; solid organ malignancy; haematological malignancy, autoimmune disease; transfusion dependence; liver disease, renal failure, haemolytic anaemia.

Results
The most common causes of hyperferritinaemia were infection (31%), solid organ malignancy, (28%), haematological malignancy (23%), and liver disease (22%). Peak ferritin concentration did not appear to be strongly associated with the factors that caused it. To explore the diagnostic utility of ferritin to distinguish autoimmune processes, infection, malignancy, and liver disease, an association between these factors and maximum ferritin concentration was tested for using Fisher’s exact test. No statistically significant association was found (p = 0.8967).

Conclusion
We found no association between maximum ferritin concentration and the causes thereof, however this study does not elucidate the diagnostic utility of hyperferritinaemia since most of the patients studied had established diagnoses before their hyperferritinaemia was identified. Hyperferritinaemia appears to be a marker of severe disease, in that most of the patients studied had died by the time of data collection.

Disclosures
T. Fieldman None. L. Stimson None. S. Zeb None. S. Alderson None. M. Lloyd None.
EP26 Do early synovitis clinics triage patients with RA affectively?
Authors: Cleaton Natasha , Khan Tahir , Raizada Sabrina R 
Published: April 2020

Abstract

Background
In 2013, the UK National Institute for Health and Care Excellence (NICE) published quality standards for the treatment of rheumatoid arthritis (RA); emphasising the importance of early diagnosis and treatment of RA and these were updated in 2018. NICE quality statement 1 recommends that patients with a suspected inflammatory arthritis are referred to a rheumatology service within 3 working days of presentation. Quality statement 2 recommends that these patients are assessed in a rheumatology service within 3 weeks of referral. In view of these quality standards and the benefit of treating patients with RA, early Early Synovitis Clinics (ESC) were set up at the Royal Wolverhampton Trust (RWT). GPs were invited to refer patients electronically to the ESC if they had a swollen joint, positive antibodies (RhF or anti CCP) and if they suspected RA. All referrals to the ESC and all other new patient referrals were triaged by a consultant rheumatologist to determine if they were suitable for the ESC.

Methods
This is a retrospective service evaluation based on new patients seen in the ESC at the RWT over a 12month period, January to December 2018. The electronic records of patients seen in the ESC were retrospectively accessed and data was collected including gender, age and diagnosis.

Results
284 new patients attended the ESC in 2018; 186 (65.49%) were female, 98 (34.51%) were male. The patients age ranged 18-95years with a mean age of 58.75. 72 patients (25.4%) were classified as having RA. 135 patients (47.54%) were classified as having inflammatory arthritis, diagnoses within the inflammatory arthritis group were: psoriatic arthritis, crystal arthritis, Palindromic rheumatism, polymyalgia rheumatica, Reactive arthritis and undifferentiated inflammatory arthritis. 84 patients (29.58%) patients received a diagnosis of osteoarthritis, 12 patients (4.22%) were classified as having a connective tissue disease, 44 (15.49%) of the 284 patients were diagnosed with a condition classified in the category of soft tissue rheumatism.

Conclusion
This analysis found while 47.54% of patients referred to the ESC at RWT received a diagnosis categorised as inflammatory arthritis, only 25.4% of patients had RA. This compares to the recent National Early Inflammatory arthritis audit where only 35% of patients seen in rheumatology clinics with suspected inflammatory arthritis had a subsequent confirmed diagnosis of an inflammatory arthritis. This suggests more guidance needs to be provided to primary care services regarding the indications for referral to the ESC in order to provide appropriate capacity for patients with RA to be reviewed and treated quickly.

Disclosures
N. Cleaton: None. T. Khan: None. S.R. Raizada: None.
O27 Early experience with JAK inhibitor prescribing in the UK: results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis (BSRBR-RA)
Authors: Kearsley-Fleet Lianne , Davies Rebecca , Watson Kath , Lunt Mark , Hyrich Kimme L ,   the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis (BSRBR-RA)
Published: April 2020

Abstract

Background
In 2017, a new class of oral disease modifying anti-rheumatic drugs (DMARDs), janus kinase inhibitors (JAKi), were licensed for rheumatoid arthritis (RA): baricitinib and tofacitinib. In the UK, they are approved for use in patients with high disease activity with or without methotrexate, following failure of conventional synthetic (cs) DMARDs or biologic DMARDs, the latter when rituximab is contraindicated. As a new therapy option, it is currently unclear how and when these drugs are being prescribed in patients with RA. This analysis aims to describe the characteristics of patients starting JAKi and registered with the BSRBR-RA.

Methods
The BSRBR-RA aims to capture exposure and outcome data in patients with RA receiving biologics, biosimilars and targeted synthetic DMARDs. At the start of therapy, demographic and clinical data, including past treatment data, are collected. Characteristics of all patients receiving a JAKi for the first time with data recorded in the BSRBR-RA up to 31/03/2019 are described.

Results
To 31/03/2019, 698 patients in the BSRBR-RA have been treated with a JAKi; 596 patients baricitinib and 110 tofacitinib (Table 1). A quarter of patients received a JAKi with no prior biologic exposure; 148 (25%) baricitinib and 16 (15%) tofacitinib. Of these, 15% had a prior malignancy history. Of those with prior biologic exposure, the median number of previous biologics was 3 (IQR 2-4), the majority had prior TNFi (91%) or rituximab (51%), and 50% were receiving concurrent methotrexate.

Conclusion
To date, more patients have been recruited starting baricitinib than tofacitinib, likely owing to the later licensing of tofacitinib. Two groups are emerging with a quarter of patients receiving JAKi immediately after csDMARDs and a majority as a later stage alternative following multiple biologics. Further recruitment and follow-up patients will allow for analysis of real-world safety and effectiveness, but differences in patient characteristics will need to be considered in any comparative effectiveness analyses.

Disclosures
L. Kearsley-Fleet None. R. Davies None. K. Watson None. M. Lunt None. K.L. Hyrich Honoraria; AbbVie. Grants/research support; UCB, Pfizer, BMS.
O40 Trends in incidence of GCA in the UK
Authors: Barnett Lauren A , Helliwell Toby , Jordan Kelvin , Prior James 
Published: April 2020

Abstract

Background
Giant cell arteritis (GCA) is the most common form of medium and large vessel vasculitis. Diagnosis remains difficult since there are a multitude of symptoms experienced by patients with GCA and if not promptly identified or treated, patients with GCA are at risk of irreversible visual loss. Therefore, a clear understanding of recent trends in incidence is important for clinicians, researchers and policy-holders to better understand and address future healthcare resource needs. Our objective was to estimate the annual UK incidence of GCA and assess whether this is changing over time.

Methods
We used the Clinical Practice Research Datalink (CPRD), a database of routinely recorded primary care records from across the UK. CPRD is representative of the UK population and contains patient information from approximately 15% of the UK population. For each year from 1992-2017, the number of patients with a first Read coded record of GCA in that year, and aged 40 years or older at the time of diagnosis, was determined. The annual denominator population included the registered practice population without a prior record of GCA, aged 40 years or older. Annual incidence per 10,000 person-years (P-Y) at risk was derived overall and stratified by age, gender and region of the UK. Trends over time were modelled using Joinpoint regression. To be confident of the primary care diagnosis of GCA, a sensitivity analysis was undertaken which included a prescription of corticosteroids alongside the GCA Read code.

Results
There was a decrease in annual incidence of GCA in the UK between 1992 and 2017. Incidence was highest in 1994 (2.29/10,000 P-Y; 95% CI: 1.96, 2.67). This decreased to 1.51/10,000 P-Y in 2006, after which the incidence rates stabilised. Incidence rates for women were higher than men, irrespective of year. Incidence peaked between 70 and 89 years of age, with females aged 70-79 having the highest overall incidence rate of 5.20/10,000 P-Y (95% CI: 5.00, 5.40). The region of the UK with the highest incidence rate of GCA from 2015-2017 was Yorkshire & the Humber with 2.63/10,000 P-Y. The regions with the lowest incidence of 1.13/10,000 P-Y were the North East and West Midlands. Sensitivity analysis gave similar patterns.

Conclusion
The incidence of GCA in the UK has decreased slightly in recent years, which may reflect developments in more definitive early GCA diagnosis through fast-track clinics and improvements in imaging. However, further research into the presenting features of GCA in primary care is required. A set of early clinical features and comorbidities that are positively associated and predictive of a subsequent diagnosis of GCA would improve diagnosis and avert significant complications associated with delayed treatment.

Disclosures
L.A. Barnett None. T. Helliwell None. K. Jordan None. J. Prior None.
P03 Effectiveness and tolerability of Benepali in patients switched from Enbrel with rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthropathy
Authors: Yeo Brandon , Dyball Sarah , Low Audrey 
Published: April 2020

Abstract

Background
Benepali (SB4) is an etanercept biosimilar licensed for rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthropathy (AS) and is cheaper than Enbrel (ETN). We aimed to evaluate the effectiveness and tolerability of switching from ETN to SB4 and costs saved.

Methods
All patients on ETN were identified from pharmacy records and reviewed by consultants for clinical suitability to switch to SB4. Letters informing patients of the proposed switch were sent and replies collated. Patients were switched when prescriptions were due for renewal. Switching started in June 2018 and patients were prospectively followed at 3 and 6 months after switching. Anonymised demographic and clinical data were collected from patient records. DAS28 was calculated for RA and PsA due to availability of score components from patient records. The difference between disease activity scores prior to the switch, 3 months, and 6 months after switching was analysed using the Wilcoxon signed-rank test.

Results
113 patients were prescribed ETN and 17 patients were clinically unsuitable to switch. Of the remaining 96 patients, 6 declined switching and 7 stopped ETN before switching. The remaining 83 patients were switched from ETN to SB4 over a year and analysed (Table 1). Comparing measures of disease activity prior to switching versus 3 months or 6 months of follow-up on SB4, there were no statistically significant differences in disease activity for patients with RA (Table). Missing data for PsA and AS precluded statistical comparisons. 5 patients switched back to ETN due to subjective worsening of joint symptoms. 3 patients switched back to ETN due to adverse effects (infections, dizziness and nausea, unknown). 1 patient switched from SB4 to abatacept due to high disease activity. 1 patient stopped SB4 due to incident lung cancer.

Conclusion
SB4 was generally well tolerated with a retention rate of 88% (73/83) over 6 months of follow-up. In RA there was no significant difference in patients’ disease activity when switching from ETN to SB4, at 3 or 6 months of follow-up. Assuming all 73 switched patients remained on SB4 for a year, this would equate to £56,000 cost savings per year.

Disclosures
B. Yeo None. S. Dyball None. A. Low None.
P11 Review of pregnancy outcomes in patients with ankylosing spondylitis presenting to the Bart's Health High Risk Antenatal clinic: results of clinical audit and recommendations
Authors: Khudadah Mohammad , Jansz Sabrina , Saeed Aamir , Bickerstaff Maria 
Published: April 2020

Abstract

Background
Most patients with ankylosing spondylitis are diagnosed in their reproductive years and pregnancy can pose a challenge for the physician. Referral for preconception counselling, monitoring and management of these patients is best done in a multidisciplinary specialist clinic. To date, literature does not associate AS with adverse effects on pregnancy outcome. Patients can have unchanged, improved or active disease during pregnancy, however, postpartum flare is common.

Methods
We conducted a retrospective audit looking at pregnancy outcomes in patients referred to the High Risk Antenatal Clinic (HR-ANC) in our Trust between January 2014 and September 2019.

Results
A total of 18 patients with 22 pregnancies were found on our electronic system. Analysis showed an average number of visits to the clinic of 3.4 visits per patient with a median of 4. Only 45% had some form of preconception counselling prior to referral. 41% of the pregnancies were not exposed to any regular medications prior to conception. All other patients had their medications stopped after conception. 59% of pregnancies had medical induction of labour, 23% had a caesarian section. Median delivery was 39 weeks. The average birth weight was 3,022 grams, median 3,205 grams. 59% of the patients had antenatal disease flare and 45% had a postpartum flare. 32% of pregnancies did not have postpartum follow up.

Conclusion
Appropriate and thorough counselling should be offered to all patients with emphasis on disease course and management, safety of medications and neonatal vaccinations. Patients should be aware of a high chance of having active disease during pregnancy and the postpartum period. The rate of caesarian section in our patient cohort was not increased compared to the local rates in low risk pregnancies. These findings of disease activity in the antenatal and postpartum periods are consistent with published data. Good monitoring in a multidisciplinary clinic can lead to a successful outcome. Based on our findings, we are setting up a formal preconception counselling clinic for patients with AS with the following aims:
1. Family planning, including contraception advice.
2. Advice regarding medication use in the preconception, antenatal and postpartum periods.
3. Advice regarding disease course and expectations.
4. Advice regarding neonatal vaccinations, especially in patients on biological treatment.
5. Hot line for unplanned pregnancy and advice regarding medications and referral to the HR-ANC.

Disclosures
M. Khudadah None. S. Jansz None. A. Saeed None. M. Bickerstaff None.
P33 Spontaneous regression of confirmed diffuse large B-cell lymphoma after withdrawal of long-term methotrexate and infliximab therapy for rheumatoid arthritis, with concurrent discovery of rare high-grade urothelial carcinoma
Authors: Jones Bryony A , O'Callaghan Ann , Ross Emily V , Razack Aaron , Yusof Harliana , Wong Ernest 
Published: April 2020

Abstract

Background
A 73 year old man was diagnosed with diffuse large B-cell lymphoma germinal centre phenotype, after presenting with a 86x70x45mm right anterior chest wall lesion. CT CAP showed no further lymphadenopathy but identified an additional solid mass in the right ureter. The patient had been on methotrexate for 15 years and infliximab for 13 years for well controlled rheumatoid arthritis, and these were both discontinued on diagnosis of lymphoma. Within three weeks of discontinuation, the lymphomatous mass had clinically noticeably shrunk, confirmed radiologically, and on PET evaluation showed just low-grade avidity. However, the ureteric tumour was avid on PET, suggestive of second pathology. Biopsy proved high grade urothelial carcinoma with neuroendocrine differentiation. Chemotherapy to treat the urothelial carcinoma was identified as a priority, and carboplatin and etoposide chemotherapy was commenced which also has activity in lymphoma. Radiotherapy will be considered in the future, if indicated following further imaging.

Methods
A literature search was conducted on occurrence of lymphoma and urothelial carcinoma with anti-TNFα biologics.

Results
The link between methotrexate and increased risk of lymphoma is well covered in literature. Anti-TNFα biologic drugs have also been linked to lymphoma, but definitive causality is difficult to establish due to low numbers of cases and confounding factors. No cases were found in literature to associate anti-TNFα drugs with urothelial, transitional cell or neuroendocrine carcinomas. Eight case studies were found which show a temporal link between discontinuation of anti-TNFα and regression of lymphoma. Of these, six cases reported regression following withdrawal of infliximab. One case involved infliximab monotherapy, three had combination therapy with methotrexate, and two with azathioprine. One case reported discontinuation of adalimumab, with continuation of methotrexate. Histology showed two cases of low grade lymphoma, two case of Hodgkin’s lymphoma, and four cases of diffuse large B Cell non-Hodgkin’s lymphoma, similar to our patient case.

Conclusion
This patient presented with two synchronous tumours: diffuse large B cell NHL and high grade neuroendocrine carcinoma of urothelial tract. Whereas lymphoma regressed on withdrawal of methotrexate and infliximab, there was no change in the urothelial malignancy. Lymphoma regression allowed the urothelial malignancy to take priority for oncological therapy. It can be concluded that withdrawal of anti-TNF agents can allow spontaneous regression of lymphoma, and this can modify patient treatment plans.

Disclosures
B.A. Jones None. A. O'Callaghan None. E.V. Ross None. A. Razack None. E. Wong None.
P54 Development of ocular toxoplasmosis and panuveitis in a patient receiving infliximab for psoriatic arthritis
Authors: Malik Mariam , Anver Himashi , Wong Ernest 
Published: April 2020

Abstract

Background
Toxoplasma gondii is thought to infect up to a third of world’s population. Incidence rate of 0.4/100,000 has been calculated in Britain, culminating in a life-time risk of 18/100,000. Cats are primary hosts, but humans and warm-blooded animals can be infected by consumption of contaminated food/water. Although in most patients, it’s self-limiting, it can be devastating in immunosuppressed patients and may cause eye manifestations, cerebral abscesses or disseminated infection. Immunosuppressive therapies including treatment with biologics increases the risk and may also cause toxoplasmosis reactivation.

Methods
This is case of 57 year old lady with psoriatic arthritis. She has past history of congenital vision impairment in the left eye and is HLA B27 negative. She enjoyed horse-riding and had a pet dog. Initially she was started on methotrexate. Sulfasalazine was added later. Due to ongoing active disease, etanercept was used for 6 months, before being switched to cetrolizumab due to ineffectiveness. She had this for 5 months and then switched to infliximab, 3mg/kg, 8 weekly. In May 2019, she was seen by Ophthalmology for 2 weeks history of blurred vision and floaters in right eye. She was diagnosed to have panuveitis and had positive IgM for toxoplasma. Bloods revealed negative TB screen, HIV, Hep B&C, syphilis, lyme and anti-streptolysin antibody tests were negative. Infliximab levels were sub-therapeutic. She was commenced on 30mg prednisolone for possible inflammatory process secondary to seronegative arthropathy, but acute toxoplasmosis could not be excluded. Hence, she was started on azithromycin and had vitreous biopsy. Toxoplasma was detected in the sample, confirming acute infection. Methotrexate and infliximab were stopped. MRI head ruled out intracranial involvement. Following treatment of acute toxoplasmosis, adalimumab is now being considered for management of her inflammatory disease, with close monitoring by local infectious-disease team and specialist ophthalmology unit.

Results
This lady developed ocular toxoplasmosis and panuveitis, whilst on immunosuppression for psoriatic arthritis. She was a horse-rider and had exposure to dogs. Diagnosing toxoplasma in immunocompromised can be difficult. Isolation of T. gondii in tissue usually confirms diagnosis. Some forms of immunosuppressive treatment may be associated with increased risk of reactivation of toxoplasmosis but there is not much evidence to assess the relative risk of various therapies.

Conclusion
Ocular toxoplasmosis needs to be considered in patients receiving immunosupression and presenting with inflammatory eye symptoms. Management requires specialist input and close monitoring. Further research into diagnostic techniques, possibility of using prophylaxis in high-risk patients and management guidelines would be helpful.

Disclosures
M. Malik None. H. Anver None. E. Wong None.