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Background/Aims JAK inhibitors (JAKi) are relatively recently licenced for treatment of inflammatory arthritis. Therefore, long term data regarding outcomes for patients cycling through multiple JAKi are lacking. However, one recent international cohort study (Pombo Suarez et al) suggested cycling JAKi is similarly efficacious as switching to an alternative biologic DMARD after initial treatment failure. The aim of this study was to assess outcomes for patients switching JAKi in a large, UK teaching hospital. Methods This was a retrospective cohort study of patients prescribed a JAKi for inflammatory arthritis at Sheffield Teaching Hospitals. Patients who had received two or more JAKi were identified through a local biologic database. Demographic data, antibody status, concomitant medications, previous biologics, and reasons for switching therapy were collected. Results We identified 20 patients who had cycled through JAKi. The diagnosis was Rheumatoid arthritis in 75% (n = 15) of patients. The remaining patients had Psoriatic arthritis (n = 3), seronegative inflammatory arthritis (n = 1) or axial spondyloarthritis (n = 1). 95% (n = 19) of patients were female. 50% of patients used concomitant DMARD therapy and 15% were prescribed concomitant steroids. 85% (n = 17) of patients had received two JAKi and 15% (n = 3) had received three. Initial JAKi prescribed was Baricitinib in 40%, Tofacitinib in 40%, Filgotinib in 10% and Upadacitinib in 10% of patients. The most frequent reason for cycling JAKi was secondary loss of efficacy, affecting 40% (n = 8) of patients. The duration of treatment before loss of effect ranged from 6-45 months (IQR 12-31 months). 100% of these patients remain on their second JAKi with good response. 35% (n = 7) of patients stopped initial JAKi therapy due to side effects. These included gastrointestinal upset, headaches, and rash. 86% (n = 6) of these patients did not tolerate a second JAKi due to re-occurrence of the same side effect, including one patient with recurrence of the same side effect on a third JAKi. One patient who had headaches with their first JAKi has remained well on their second JAKi. 20% (n = 4) of patients changed therapy due to primary nonresponse to initial JAKi. One patient failed to respond sufficiently to either JAKi and alternative treatment was commenced. Three patients responded to a second JAKi, although two later lost efficacy and are currently responding well to a third JAKi. One patient switched JAKi due to cardiovascular risk with Tofacitinib. Conclusion This study supports recent studies in finding that cycling JAKi in patients who lose efficacy or do not respond to initial JAKi can be an effective treatment strategy. However, in patients who stop initial JAKi due to side effects, cycling to a further JAKi is less likely to be successful, with recurrence of side effects in most cases. Disclosure E.M. Quinlan: None. M. Cox: None. J.R. Maxwell: Honoraria; BMS, Pfizer, Abbvie, Lilly, Gilead.

Background/Aims Biological disease-modifying anti-rheumatic drugs (bDMARDs) account for a significant proportion of pharmaceutical expenditure in the NHS. In 2016, Manchester Royal Infirmary implemented the first Biological Rheumatology MDT to reduce variation in biologic prescribing. A similar care model was implemented in Sheffield Teaching Hospitals (STH), which we evaluate here. This evaluation aimed to answer the following questions: has the MDT improved the cost-effectiveness of biologic prescribing in STH, do anti-drug antibodies (ADAB) influence subsequent biologic treatment, are IL-6 or JAK inhibitor monotherapies more clinically effective than anti-TNF monotherapy in rheumatoid arthritis (RA) and what happens when no biologic treatment is advised? Methods The MDT keeps a real-time record of discussions containing patient demographics, previous therapies, and MDT decisions. This includes all MDT meetings over a 32-month period. This was merged with a database containing the current biologic therapy of all STH rheumatology patients, and a notes-review confirmed accuracy. For economic evaluation, a similar database was produced for patients commenced on biologics in the 6 months prior the MDTs introduction. Results Over the 32-month period of the MDT, there were 994 discussions about 796 patients. Concomitant conventional DMARD therapy was used in 63% of patients. 89% of patients discussed continue to use biologic therapies. The biologic MDT resulted in a 26% decrease in cost during the first 6 months of the MDT when compared to 6 months before the MDT. This was attributed to the increased use of biosimilars and evidence-based decision making. There was improved drug survival, with 28% of pre-MDT patients requiring a subsequent change to an alternative biologic, compared to 21% of patients in the MDT group. Secondary ADAB-positive failure is the commonest cause of ADAB-forming anti-TNF failure across all diagnoses. This commonly prompts a class switch in RA (where there are a wider range of NICE approved therapies), and a switch to etanercept (with the advantage of reduced immunogenicity when compared to other Anti-TNFs) in ankylosing spondylitis and psoriatic arthritis. IL-6 inhibitors and JAK inhibitors perform more favourably as monotherapies than anti-TNFs. 21% of patients in each of the IL6 inhibitor and JAK inhibitor monotherapy groups required alternative biologic therapy, compared to 42% in the anti-TNF monotherapy group. Of the 51 patients in whom no biologic was initially advised, 61% went on to receive a biologic. Conclusion The bDMARD MDT in STH has improved the standardisation of biologic prescribing across the rheumatology team. This evaluation has demonstrated significant improvements in cost-effectiveness and treatment retention compared to the 6-month period prior to the MDTs introduction. The evidence-base is effectively enforced by the MDT, which improves patient experience by improving drug survival. We recommend implementing a biologics MDT within other services to ensure equitable and cost-effective prescribing. Disclosure R.J. Nock: None. J.R. Maxwell: Other; JRM has served on advisory boards for Abbvie, Pfizer, BMS and Lilly and has received speaking honoraria from Pfizer, BMS, Novartis and Lilly.

Background/Aims Juvenile idiopathic arthritis (JIA) is a heterogenous, childhood-onset condition persisting into adulthood in over 50% of people. Recognition of JIA-specific features is poor in adult services, there are no validated disease activity scores for adults with JIA and specialist adult JIA clinics are rare; this leads to under-treatment of adults with JIA. Sheffield Teaching Hospitals (STH) has a mature transition service and well-established young adult clinic (YAC) for 16-25 year olds and older adults with JIA. Here, we evaluate the proportion of our adult rheumatology workload attributable to JIA, the prevalence of JIA subtypes and therapies utilised. Methods Outpatient attendances in STH rheumatology are coded by diagnosis. The evaluation period was 1.12.2018 to 27.2.2020. We evaluated the number and characteristics of patients in the JIA cohort, producing a database from coded diagnoses and patient records, and analysed this using Microsoft Excel. Local permission was granted. Results 11,520 patients were seen in adult rheumatology in the evaluation period; 9,422 had a coded diagnosis of which 4,915 (52%) had inflammatory arthritis (IA). Assuming a proportional number of the 2,098 non-coded patients had IA (1,090), the adult IA cohort is estimated at 6,005. 304 patients (aged 17-72) with JIA were seen in adult rheumatology, accounting for 5% of the adult IA cohort. 280 (92%) were in the YAC, and 24 (8%) in general rheumatology. 31 (10%) patients had evidence of uveitis. The commonest subtypes of JIA were: 75 polyarticular (25%), 38 enthesitis related (13%) and 37 extended oligoarticular (12%). 64 (21%) patients had no subtype specified. Of the 233 (77%) JIA patients ever treated with methotrexate, 132 (57%) had discontinued due to inefficacy or adverse effects. 175 (58%) patients were on biologic treatment: the commonest therapies were adalimumab (40%, 70 patients) and etanercept (27%, 47 patients). There is evidence of diagnostic relabelling from JIA to other IA to access biologics not approved by NICE. Conclusion This evaluation uses real-world data, with some data loss due to absent coding, but shows JIA is a small proportion of adult rheumatology. This is a complex group with high biologic use, poor methotrexate tolerance and heterogenous disease phenotypes. Young adults experience specific challenges in adult services and require developmentally appropriate care, for which best evidence confirms young adult clinics are ideal. The majority of people with JIA are in a dedicated young adult service at STH. Biologics are used within NICE guidance, except for a minority where JIA is relabelled as IA to access additional biologics or due to independent funding requests. NICE guidance for JIA is outdated and restrictive. JIA is an adult disease in > 50% and requires specialist services, further research to elucidate validated adult disease activity scores and wider education amongst adult rheumatologists. Disclosure R.J. Nock: None. J.R. Maxwell: Other; JRM has served on advisory boards for Abbvie, Pfizer, BMS and Lilly and has received speaking honoraria from Pfizer, BMS, Novartis and Lilly. R.S. Tattersall: Other; RST has received speaker fees and educational grants to attend meetings from UCB, AbbVie, Pfizer and Janssen.

Background Giant cell arteritis (GCA) usually affects the temporal arteries but can result in systemic vasculitis that can be seen on Positron Emission Tomography-Computed Tomography (PET-CT). Currently PET-CT is not used first line to diagnose cranial-GCA and temporal artery biopsy (TAB) remains the most common investigation to assess for this. There have been few studies performed to assess the use of PET-CT as an initial diagnostic tool in cranial-GCA. One study performed PET-CT for suspected GCA in their cohort of 64 patients. They found, when compared with TAB, global GCA assessment by PET-CT had a sensitivity of 92%, specificity of 85%, positive predictive value of 61% and negative predictive value of 98%. They concluded PET-CT had good diagnostic accuracy when compared with TAB and can be used as a first-line test to assess for GCA and rule out lower-risk GCA. Another study used PET-CT in steroid-naïve patients and also showed a high accuracy (sensitivity 64% and specificity of 100%) in diagnosing cranial artery inflammation. Methods We present two cases where the patient had symptoms of headache, constitutional symptoms and raised inflammatory markers, however PET-CT did not suggest GCA. The patients were subsequently re-referred later with ongoing symptoms and TAB confirmed GCA. Results Case 1: A 71-year-old woman presented with a one-month history of intermittent right sided headache and rigors. Her inflammatory markers were elevated (CRP of 115mg/L and ESR of 57mm/hr). Suspecting GCA, prednisolone 30mg od was commenced. Upon rheumatology review, it was felt her symptoms were atypical for GCA. Prednisolone was discontinued, and a PET-CT scan was arranged. This was performed ten days later and did not show any features of vasculitis. Six weeks later, the patient presented to ophthalmology reporting visual aura, ongoing headache with elevated inflammatory markers. Prednisolone 60mg od was commenced and a TAB was arranged. This was reported as partially treated GCA. Case 2: A 73-year-old gentleman had a prolonged admission for pyrexia of unknown origin. Headache was present throughout admission and rheumatology opinion was sought. A PET-CT did not show vasculitis. The patient was discharged when pyrexia improved however his inflammatory markers remained consistently high (CRP of 82mg/L and ESR 106mm/hr). One-month post-discharge, the patients GP contacted rheumatology concerned about ongoing headache and scalp tenderness. Prednisolone 40mg od was commenced and a TAB was arranged which reported features consistent with GCA. Both patients responded well to steroids. Conclusion As demonstrated, patients with biopsy proven GCA do not always exhibit vasculitis on imaging. A negative PET-CT did not reliably exclude GCA in our patients suggesting its use as a diagnostic investigation for GCA needs to be approached with caution. A TAB should also be performed when there is ongoing suspicion of GCA. Disclosures S. Khalid None. J. Maxwell Honoraria; BMS, Pfizer, Lilly, Abbvie. Other; Talks, BMS, Pfizer, Lilly, Abbvie.

Background Interstitial lung disease (ILD) is a serious extra-articular manifestation of rheumatoid arthritis (RA). Risk factors include smoking, the presence of rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (CCP). Pulmonary function tests (PFT) show reduced carbon monoxide diffusion capacity (DLCO) early and reduced forced vital capacity (FVC) later in disease. HRCT is the gold standard diagnostic test while chest X-ray (CXR) has low sensitivity. PFT are routinely performed in the majority of RA patients at baseline at our tertiary centre. The aim of this study was to evaluate the frequency of abnormal PFT, specificity for ILD and influence on subsequent decision-making in patients newly diagnosed with RA. Methods A retrospective analysis was undertaken of patients with a new diagnosis of RA between January 2016 and December 2017. Patients meeting the ACR (2010) criteria for RA, with baseline PFT data available were included. Clinic letters and the hospital electronic records were used to obtain the data. Results 139 patients were included in the data analysis (Table 1). 23 patients had DLCO Conclusion This evaluation suggests baseline PFT are more sensitive than baseline CXR in detecting ILD but that a DLCO Disclosures A. Haque None. R. Kilding None. R. Smith None. S. Khalid None. R. Sandler None. M. Cox None. T. Hendry None. A. Flores-martin None. K. Lindop None. J. Maxwell None.

Objectives To investigate the association between genotype at the soluble interleukin 6 receptor (sIL-6R) A358C single nucleotide polymorphism (SNP, rs8192284), previously reported to correlate with soluble receptor levels, and response to anti-TNF therapy in subjects with RA. Methods In a large cohort of Caucasian RA patients treated with anti-TNF medications (total, n = 1050; etanercept, n = 455; infliximab, n = 450; and adalimumab, n = 142), the sIL-6R A358C polymorphism was genotyped using a Taqman 5'-allelic discrimination assay. Linear regression analysis adjusted for baseline 28 joint disease activity score (DAS28), baseline HAQ score, gender and use of concurrent DMARDs was used to assess the association of genotype at this polymorphism with response to anti-TNF therapy, defined by change in DAS28 after 6 months of treatment. Analyses were performed in the entire cohort, and also stratified by an anti-TNF agent. Additional analysis according to the EULAR response criteria was also performed, with the chi-squared test used to compare genotype groups. Results No association between genotype at sIL-6R A358C and response to anti-TNF treatment was detected either in the cohort as a whole or after stratification by anti-TNF agent, in either the linear regression analysis or with response segregated according to EULAR criteria. Conclusions This study shows that genotype at the functional sIL-6R A358C SNP is not associated with response to anti-TNF treatment in patients with RA.

Dawn Johnson Bernadette Hardware Mwidimi Ndosi Tracey Young Claire Hale James Maxwell Euthalia Roussou Ade Adebajo