bluuebunny/crossref_metadata_2025 huggingface dataset:
OA05 Harnessing high throughput multiplex immunoassays and protein association networks to identify diagnostic protein biomarkers of rheumatoid arthritis-cardiovascular disease (RA-CVD) multimorbid axis
Authors: Shukla Rudresh , Black Nicholas , Plant Darren , Miller Christopher , Plein Sven , Buch Maya H
Published: April 2023

Background/Aims

People with rheumatoid arthritis (RA) have higher mortality rates compared to the general population, primarily due to excess cardiovascular (CV) disease (CVD). The earliest stages of RA are associated with CV abnormalities but biomarkers to identify CVD in early RA are lacking. We aimed to identify focused protein biomarkers that associate with cardiac magnetic resonance imaging (CMR) abnormalities in a treatment-naïve, new-onset RA trial cohort and the predominant inflammatory and metabolic pathways involved in RA-CVD.

Methods

CADERA (Coronary Artery Disease in Early RA) was a bolt-on study to a parent RCT in an early RA inception cohort. 81 treatment-naïve early RA patients underwent CMR at baseline as part of CADERA. Proximity extension immunoassay (OIink) was used to measure normalised protein expression across inflammation, cardiovascular II/III and cardiometabolic panels in CADERA patients. Bayesian mixed effects linear regression was used to identify significant proteins associated with CMR parameters of myocardial oedema/fibrosis and vascular stiffness at baseline. Then, an expanded protein-protein interaction (PPI) network using above proteins was created using an induced network approach (String-DB) and k-means clustering applied to identify protein clusters that were subsequently subjected to Gene ontology (GO) and KEGG enrichment analysis.

Results

Of 340 proteins analysed using Olink, 108 proteins were associated with CMR markers of myocardial fibrosis/oedema (64 proteins) and vascular stiffness (44 proteins) Table 1 highlights the top 5 proteins for each CMR parameter.

K-means clustering of the expanded PPI network identified 4 clusters with roles in vascular endothelial growth factor receptor binding and JAK-STAT signalling pathway (cluster 1); IL27 receptor binding and NF-kappa B signalling pathway (cluster 2); Macrophage CSF receptor binding and ErbB signalling pathway (cluster 3); and IL10 receptor activity and complement and coagulation cascades (cluster 4).

Conclusion

This is the first study to identify protein biomarkers of RA-CVD, an area of unmet clinical need, using a combination of targeted high throughput immunoassays, Bayesian and network analyses. Targeted techniques such as Olink may help identify potential diagnostic biomarkers of RA-CVD. Pathway analysis provides insight into the inter-relationship between inflammation and metabolic mediators of RA-CVD axis.

Disclosure

R. Shukla: None. N. Black: None. D. Plant: None. C. Miller: None. S. Plein: None. M.H. Buch: None.
OA21 Use of the patient activation measure in rheumatology outpatients
Authors: Wood Claire R , Dale James E
Published: April 2023

Background/Aims

Our rheumatology department is considering introducing patient-initiated follow-up (PIFU) for patients with stable inflammatory conditions. This will require patients to be motivated and appropriately seek help when required. The 13-item Patient Activation Measure (PAM-13) is a tool that measures patients' knowledge, skills and confidence in managing their health and is categorised into levels of increasing activation - level 1 (disengaged and overwhelmed), level 2 (becoming aware, still struggling), level 3 (taking action), and level 4 (maintaining behaviours, pushing forwards). Our aim was to describe the distribution of patient activation scores in a cross section of patients attending rheumatology return appointments.

Methods

Clinic patients were asked to complete a form which comprised demographic and disease background information, the PAM-13 and the Arthritis Self Efficacy Score (ASES). All data were anonymised. Demographic details included age, sex, postcode (for Scottish Index of Multiple Deprivation (SIMD) calculation), educational attainment, employment status, living situation, and requirement for assistance with activities of daily living (ADLs). Disease related details were main rheumatological diagnosis, years since diagnosis, patient opinion of disease control, and global health visual analogue score (VAS). Patient Health Questionnaire 2 (PHQ-2) and Generalised Anxiety Disorder 2 (GAD-2) were used to screen for mental ill-health.

Results

A total of 209 responses were collected. Patients fell into the following activation levels: level 1 - 25.4%, level 2 - 32.5%, level 3 - 24.4%, and level 4 - 17.7%. Patients in level 1 were compared to patients in levels 2 - 4 to establish trends.

Those in level 1 less frequently felt that their rheumatic disease was well controlled (52.8% vs 72.4%). Level 1 patients were more likely to live in the most deprived areas (41.5% in SIMD quintile 1 vs 26.9%); had lower rates of full or part time employment (22.7% vs 53.2%) and higher rates of unemployment due to disability (22.6% vs 8.3%); had lower rates of educational attainment (11.3% with university education vs 21.8%); more frequently required assistance with their ADLs (62.3% vs 26.3%) and reported higher levels of depression (58.5% vs 25.6%) and anxiety (41.5% vs 24.4%). Level 1 patients reported lower global VAS (median 50 vs 70) and lower ASES (median 3.8 vs 6).

Conclusion

57.9% of our patients fell into low activation levels 1 and 2. Those in the lowest activation group had the highest proportion of patients from areas with high rates of deprivation, lowest rates of employment and higher educational attainment, and highest rates of requiring assistance with ADLs, depression and anxiety. The converse was true for those in the highest level of activation group. These patients may not be appropriate for new PIFU or may require additional, tailored support for it to be safely implemented.

Disclosure

C.R. Wood: None. J.E. Dale: None.
OA22 Management of haemophagocytic lymphohistiocytosis: service evaluation of a national multi-disciplinary meeting
Authors: Shah Neal S , Hutchinson Matthew , Clark Samuel , Sanchez Emilie , Brown Michael , Stone Neil , Carr Aisling S , Carpenter Ben , Laurence Arian , Gohil Satyen H , Tattersall Rachel S , Manson Jessica J , Jones Alexis
Published: April 2023

Background/Aims

Haemophagocytic lymphohistiocytosis (HLH) is a devastating condition caused by uncontrolled activation of the immune system. If left untreated, the condition leads to multi-organ failure and death. Even with treatment, recent UK data has shown a mortality rate of 50%. In 2019, a group of clinicians from University College London Hospital (UCLH) came together with the aim of improving outcomes for patients with HLH. The UCLH HLH multi-disciplinary meeting (MDM) has been running since that time and includes representation from rheumatology, haematology, infectious diseases, tropical medicine, virology, neurology, and critical care. Clinicians from any UK trust are invited to join and present patients. As part of a service evaluation project, we aimed to assess the scope of this meeting with regards to the number, demographics and primary diagnoses of patients discussed and the geographical location of the referring clinical team.

Methods

This is a retrospective descriptive analysis of all patients discussed at the UCLH HLH MDT from 2nd September 2020 to 20th July 2022. Data were obtained from electronic health records and analysed in Prism version 9.4.1. This work has been registered as a service evaluation project within the Division of Medical Specialities at UCLH.

Results

93 patients were discussed. 38 were female. 55 were male. The median age was 38 years. Triggers for HLH were haematological malignancy (38.0%), infection (29.3%) rheumatological (14.1%) primary HLH (6.5%) and unknown (7.6%). In 4 patients, HLH was not felt to be the underlying diagnosis. 40 patients were managed as inpatients at UCLH, 37 of whom were transferred from other trusts. Geographical data were obtained on 81 patients. Patients were referred from all 9 regions of England: London (34), North East (1), North West (2), Yorkshire (2), East Midlands (1), West Midlands (3) South East (11), East of England (11), South West (11) as well as Wales (2), Scotland (2) and Ireland (1). Haemophagocytosis was confirmed on bone marrow biopsy in 66.7% of patients. Mortality data showed that 32 (34%) patients died following their diagnosis.

Conclusion

A multi-disciplinary approach is essential in the management of HLH. Our data show that patients with HLH are young, have a high mortality and broad range of pathology. The UCLH HLH MDT currently serves a wide geographical area across the UK and UCLH acts as a tertiary referral centre for patients with the condition.

Disclosure

N.S. Shah: None. M. Hutchinson: None. S. Clark: None. E. Sanchez: None. M. Brown: None. N. Stone: None. A.S. Carr: None. B. Carpenter: None. A. Laurence: None. S.H. Gohil: None. R.S. Tattersall: None. J.J. Manson: None. A. Jones: None.
OA33 The incidence of large vessel vasculitis in Norfolk
Authors: Mukhtyar Chetan B , Beadsmoore Clare , Coath Fiona , Ducker Georgina , Sisson Katherine , Watts Richard A
Published: April 2023

Background/Aims

There are no data on the collective incidence of the large vessel vasculitides. The incidence of GCA and Takayasu arteritis in the UK has been based on clinical coding in routine administrative datasets. There are no data on the incidence of these diseases based on clinically verfied diagnoses. We studied the incidence of the large vessel vasculitides in a stable population with a predominant Northern European ancestry.

Methods

Individuals attending a secondary care hospital with a clinically verified diagnosis of primary systemic vasculitis made between 2011-2020, who lived within the NR postcode districts of Norfolk county were included if they met classification criteria for GCA or Takayasu arteritis, or had definite tissue or imaging evidence of large vessel vasculitis. Population above the age of 18 as in the 2011 census, available from the office of national statistics, was accepted as the denominator. If classification criteria for both GCA and TAK were met, physician judgement was accepted as final diagnosis.

Results

272 adults were diagnosed with large vessel vasculitis out of a population of 454,316. The annual incidence of large vessel vasculitis in Norfolk is 59.9/million in the adult population. The annual incidence of GCA is 9.9/100,000 over the age of 50 using the ACR 1990 criteria and 10.6/100,000 using the ACR/EULAR 2022 criteria. The rise in the incidence from 2017 onwards coincides with the establishment of a fast-track pathway (Table 1). The dip in the incidence in 2020 coincides with suspension of services during the SARS-CoV-2 pandemic. The annual incidence peaks at 168.5/100,000 in the 9th decade and is commoner in females (12.3/100,000 vs 7.3/100,000). The annual incidence of Takayasu arteritis is 3.3/million in the adult population using the ACR 1990 criteria and 1.1/million using the ACR/EULAR 2022 criteria.

Conclusion

This is the first study that reports the incidence of all objectively diagnosed large vessel vasculitis in a stable population in Norfolk county. The incidence of GCA rose with the establishment of a fast-track pathway and its peak may have been affected by the SARS-CoV-2 pandemic. GCA is commoner in females and peaks in the 8th and 9th decades.

Disclosure

C.B. Mukhtyar: None. C. Beadsmoore: None. F. Coath: None. G. Ducker: None. K. Sisson: None. R.A. Watts: None.
P011 Rituximab and COVID-19 vaccines; are they fit for purpose?
Authors: Stewart Sarah K , Pendleton Adrian
Published: April 2023

Background/Aims

Since the COVID-19 outbreak the rheumatology community have been concerned about the risk of SARS-CoV-2 infection in patients prescribed immunosuppressing medications. Data suggests that patients receiving Rrtuximab are at increased risk of developing severe outcomes from COVID-19 (1). In our unit all patients receiving rituximab were selected to receive a targeted vaccination and booster programme with all patients receiving at least 2 vaccinations and up to 3 booster vaccinations. We studied the efficacy of the COVID-19 vaccines in rituximab patients, by checking the the Roche Elecsys Anti-SARS-CoV-2-S (Spike) IgG/IgM total antibody levels post vaccination. Our aim was to assess the vaccination response in patients receiving rituximab and to offer advice on continued shielding or alternatively passive immunization with tixagevimab/cilgavimab in those patients who did not mount a response.

Methods

Taking 39 patients currently on rituximab therapy, we measured Anti-SARS-CoV-2-S (Spike) antibody levels post vaccination. We recorded whether the test was positive or negative, and the numerical result. We recorded rituximab dates of administration and dates of vaccines. We also recorded diagnosis, co-prescribed DMARDs, immunoglobulin levels, white cell and lymphocyte counts. We took record of whether or not the patient subsequently contracted COVID-19, required a hospital admission, ICU or died.

Results

Of our 39 patients, 21 had Anti-SARS-CoV-2-S (Spike) antibody levels checked. Of these patients, 7 (33%) had a negative spike protein result. Of the patients with a positive result, 8 (38%) had an antibody level between 0-250U/ML, and only 6 (28.6%) had a level >250U/ML (The manufacturer advises that a level above 0.8U/ML is a positive result). Of patients with a negative result, 1 patient had received 3 vaccines, 5 patients had received 4, and 1 patient had 5. All of the patients had received a vaccine >4 weeks prior to receiving the drug. Two patients were co-prescribed Belimumab, 3 were co-prescribed low-dose methotrexate and 2 were not on additional disease modifying agents. The diagnoses of these patients were, 2 patients with SLE, 4 with SPRA, and 1 MPO Vasculitis. There were no significant findings in lymphocyte count, white cell count or immunoglobulin levels.

Conclusion

These findings suggest that our current COVID-19 vaccination and booster programme may not provide adequate response in patients receiving rituximab therapy. Despite this being a small cohort, these results show that 33% of patients have not mounted a vaccine response and this is concerning. We suggest that vaccine response should be checked in all patients receiving rituximab therapy and those patients who do not mount a vaccine response should be offered passive immunity and advised of possible additional risks regarding COVID-19 exposure.

Disclosure

S.K. Stewart: None. A. Pendleton: None.
P016 To rescreen or not to rescreen, that is the question: an evaluation of practice of rescreening for infections when switching advanced therapies in rheumatology patients
Authors: Masood Ammara , Xiang Yawen , Rose-Hartwell Safiya , Subesinghe Sujith
Published: April 2023

Background/Aims

The 2018 British Society for Rheumatology guidelines mandate pre-treatment screening for infections (including tuberculosis [TB], viral hepatitis and HIV) in patients prior to treatment initiation with advanced therapies. It is increasingly common for patients to switch advanced therapies due to inefficacy or intolerance. There is no established guideline stipulating the frequency of rescreening patients for infections when switching advanced therapies. Rescreening is expensive and can delay the prescribing process. This audit reviewed the current practice at a single tertiary rheumatology centre.

Methods

A retrospective case note analysis of 100 consecutive patients who underwent biologic switch between April 2021 to March 2022 was included. Data extraction included patient demographics, rheumatic diagnosis, drug exposures, co-morbidities including past infections and rescreening tests were undertaken (including T-SPOT.TB, chest X-ray and serological tests for hepatitis B, C and HIV).

Results

The median age of this cohort (64 female, 36 male) was 53 (IQR 41 - 60). The most common diagnosis was rheumatoid arthritis (n = 62), followed by psoriatic arthritis (n = 27) and ankylosing spondylitis (n = 7). Seven patients were identified as high-risk individuals: two patients with hepatitis B, one with latent TB, one with previous positive TSPOT.TB and three with underlying lung diseases. 69 patients were partially rescreened for infections and 21 patients had a complete re-screen including chest X-ray, TSPOT.TB, HIV serology, HBsAg, Anti-HbC and Anti HCV. 31 patients did not have any re-screening tests when switching to a different biological drug. The range since the previous pre-advanced therapy screening was between 6 months and 5 years. There was no significant difference in the rate of rescreening investigations between those who switched drugs within the same class, versus those switching drug classes (p = 0.874). No new infections, active or latent, were identified on rescreening. The total cost involved in rescreening this cohort of patients was estimated at £5930.

Conclusion

Our audit data showed that rescreening for infections at 18 months or less has a low yield for identifying new incident infections. The decision to rescreen patients was primarily driven by the clinician’s judgement. It is pertinent to standardise the practice by establishing an evidence-based guideline based on a robust risk assessment which may then lead to long-term cost-savings.

Disclosure

A. Masood: None. Y. Xiang: None. S. Rose-Hartwell: None. S. Subesinghe: None.
P032 Starting work as a rheumatology doctor: how to do it well
Authors: Benson Rosalind , Appleby Edward , Gledhill-Flynn Charlie , Maxey Kate , Southam Daisy , Little Jayne , Watson Pippa A
Published: April 2023

Background/Aims

Starting work in a specialty for the first time can be extremely challenging. This has implications for patient care, junior and supervising doctor enjoyment and future career choices. A focus group was established to explore what resources junior doctors would want when starting Rheumatology. This determined that a blended learning package with podcasts, webinars and eLearning with topics including history and examination skills, understanding investigations and prescribing disease modifying drugs (DMARDs) would be ideal. Furthermore, it would be well placed to include resources to help junior doctors consider a career in Rheumatology.

Methods

The focus group results were used to design online ‘how to’ resources guiding doctors through tasks that they might be expected to do as a Rheumatology doctor. These were created by teams of junior doctors alongside Consultant Rheumatologists with creative support from the British Society for Rheumatology (BSR) education team. Content was pitched at an introductory level to help doctors when they first start working in Rheumatology. The most appropriate delivery modalities were selected for each topic e.g. a podcast for ‘how to talk to patients about DMARDs’ and eLearning including a video for ‘how to do disease activity scoring’. The resources are hosted on the BSR eLearning site and are free for anyone to use (no membership required) https://www.rheumatology.org.uk click eLearning. BSR communications and twitter were used to advertise the launch of the ‘how to’ series prior to junior doctor rotations in August.

Results

Since the ‘how to’ eLearning site was launched there have been 258 users. All content has been accessed. To date the most popular topics have been ‘how to’

- Interpret antibodies-Use DMARDs safely-Interpret x-rays-Score disease activity

Feedback has been extremely positive with an overall satisfaction of 4/5. An example of written feedback from a user “ … it was a good overview, I would recommend to new IMT doctors starting in departments, or those considering Rheumatology as a career, I like how you have incorporated different modalities for learning e.g. mixture of lectures, podcasts, reading.”

Conclusion

The response to the resources created so far have been extremely positive. 258 users is a good start but increasing awareness of the resources should allow many more doctors to benefit from these resources. The authors plan to develop and improve content and welcome any feedback or suggestions for future topics.

Disclosure

R. Benson: None. E. Appleby: None. C. Gledhill-Flynn: None. K. Maxey: Other; Kate is a member of the Education team at the British Society for Rheumatology. D. Southam: Other; Daisy is employed by the British Society for Rheumatology as Head of Education. J. Little: None. P.A. Watson: Other; I am employed by the British Society for Rheumatology as eLernaing Editor.
P061 COVID vaccine made my joints hurt: effect of COVID vaccine on systemic rheumatic disease
Authors: Munir Asif , Awais Hafiz
Published: April 2023

Background/Aims

Vaccination against SARS-CoV-2 is crucial for patients with systemic rheumatic diseases (SRDs) who may be at increased risk of severe outcomes post-COVID-19. Sparse data suggests vaccines used for COVID -19 may be associated with SRD flares, possibly from molecular mimicry triggering immune activation or non-specific adjuvant effects. As SRD flares are associated with disease deterioration, increased flares could have serious clinical implications. We report the interim results of a survey evaluating SRD flare incidence post-SARS-CoV-2 vaccine.

Methods

We surveyed 200 patients of different age group with different SRDs via telephone or paper copy during their appointment in Rheumatology department at North Cumbria Integrated Care NHS Foundation Trust, from September 2022 to March 2022 who received at least one dose of Pfizer or Astra Zeneca vaccine. The results of the survey were recorded.

Results

The mean age of the patients was 62.5 years. 63% of the patients (N-126) were females. 53 (26.5 %) of these patients had Rheumatoid Arthritis (RA), 43 (21.5 %) had Psoriatic Arthritis, 37 (18.5%) had Sero-ve Spondyloarthropathy, 22 (11%) had Ankylosing Spondylitis, 16 (8 %) had CTD, 12 (6%) had PMR, 10 (5%) Vasculitis and 7 (3.5%) had Palindromic arthritis. 96 (48%) of these patients were on synthetic DMARDs, 56 (28%) on Biologic DMARDs and 41 (20.5%) were on combination. 7(3.5%) patients were on NSAIDS. The most common adverse effects from the vaccine were pain at the site of injection and generalized body aches in 90 % of patients followed by fatigue in 80%. 22% had fever. 21 (10.5 %) patients had flare up of their existing rheumatic disease after the first dose and 22 (11%) had a flare after 2nd dose and another 24 (12%) after the 3rd dose. 30 (15%) patients had some flare up after two doses. Out of these 26 had mild flare up and improved with Paracetamol/codeine. 30 had mild to moderate flare required different NSAIDs and 21 had severe requiring a course of prednisolone. 3 of these patients required step up of DMARDS. These flares were described as typical, suggesting these symptoms were not vaccine’s adverse effects being misreported as disease flares.

Conclusion

Interim data from our cohort demonstrates about 12% of patients had severe flare up, with some lasting for weeks requiring switching of DMARDs.

Although SARS-CoV-2 vaccine might be associated with some flare up in SRD, but the morbidity and mortality of non-vaccinated patients with SRD can be very devastating signifying the importance of the vaccine. Further data is required for a wider cohort.

Disclosure

A. Munir: None. H. Awais: None.
P092 Imagined Futures: How can digital storytelling empower young people with JIA to engage in ideas about health, wellbeing and transition
Authors: Woolf Anna , Wilson Debbie
Published: April 2023

Background/Aims

During February half-term 2022, seven young people with JIA ranging in age from 11 to 16 coalesced at the Unicorn Theatre in London to participate in a week-long series of workshops exploring filmmaking, digital storytelling, and health. Led by Creative Health PhD researcher Anna Woolf (Royal Central School of Speech and Drama), and Debbie Wilson, Young People’s Project Manager from JIA-at-NRAS, the facilitators engaged the young people in a series of digitally-led practices which allowed the young people to explore their lived experiences in a creatively-led group setting. Utilising TikTok methodologies (Pomerantz, 2021) the young people created and performed content that explored themes of identity and emerging self-hood. The project enabled young people’s understanding of their JIA to be explored in relation to their hopes and fears about their future health, self-management, and ideas about transition.

Methods

The approach included pre-project qualitative and quantitative surveys detailing young people’s attitudes and experiences to having JIA, semi-structured interviews with the young people and thematic qualitative analysis of filmed stories.

Results

Young people expressed that they had never met another young person with JIA or arthritis ever before despite several of them attending the same paediatric centres such as Great Ormond Street or the Evelina hospital in London. The project coalesced young people around their collective health conditions and the use of digital mediums made space for places of powerful solidarity between young people experiencing the same health problems.

Conclusion

Despite young people with JIA having good relationships generally with their doctors and support from their families, the work created by them in the project showed the researcher very clearly that they need much better peer support structures, help and understanding from other adults such as teachers, and in general, more understanding and empathy from the world at large about their lived experience. Utilising TikTok, filmmaking and online creative formats such as meme-making and online journaling, the young people were clearly engaged and adeptly expert at producing creative testimony and performance which illustrated their experiences of health. Assumptions such as believing that young people struggled with their patient-doctor relationships were replaced with a real understanding of the young people’s struggles, such as learning that teachers and other adults in the world are far more problematic, oftentimes labelling them as lazy or difficult for not participating in life in ways that their fully able-bodied peers do. The researcher also learnt much more about the effects of poor mental health that JIA engenders for young people with arthritis and reflected on the need for more creative peer-led spaces to explore this.

Disclosure

A. Woolf: None. D. Wilson: None.
P126 Cycling of JAK inhibitors: Experience from a large UK teaching hospital
Authors: Quinlan Eavan M , Cox Miriam , Maxwell James R
Published: April 2023

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.
P137 First-line tumour necrosis factor inhibitor (TNFi) treatment is associated with high multi-criteria remission early on compared to treat-to-target in a treatment naïve RA cohort
Authors: Shukla Rudresh , Plant Darren , Emery Paul , Buch Maya H
Published: April 2023

Background/Aims

In rheumatoid arthritis (RA) disease assessment, SDAI and Boolean remission criteria are known to be more stringent in comparison to DAS28-ESR. Comparing remission rates across multiple assessment indices provides a more comprehensive evaluation of disease control. In an early RA trial cohort, we aimed to investigate stringent and multi-criteria remission (MCR) rates and evaluate their proportional change in response to treatment.

Methods

The ‘VEDERA’ trial randomised 120 treatment-naïve, new-onset RA patients to first-line etanercept+methotrexate (ETN+MTX) or methotrexate treat-to-target (MTX-TT) with escalation to ETN+MTX if not in DAS28-ESR remission at week24. Clinical assessments were completed at baseline, weeks12/24/48 (protocolised phase) up to week96 (standard-of-care). Remission cut-points included: DAS28-ESR ≤2.6, SDAI ≤3.3 and Boolean score for individual components≤1. MCR was defined as patients who were in DAS28-ESR, SDAI and Boolean remission concurrently. Descriptive analyses were undertaken to address the above aims.

Results

Overall, at week12, 26%(31/120) were in SDAI and 13%(16/120) in Boolean remission. This increased to 41%(49/120) and 23%(28/120) respectively by week48.

In the ETN+MTX group at week12, 30%(18/60) were in SDAI and 17%(10/60) in Boolean remission. This increased to 43% (26/60) and 32%(19/60) respectively by week48. Stringent remission rates were lower in MTX-TT compared to ETN+MTX and significantly different for Boolean at week48 (15% vs 32%, odds ratio 2.6, 95% confidence interval 1.1 to 6.5, nominal p < 0.05) (Table 1).

Of those in remission by the three different criteria, 36%(14/39) were in MCR at week12, with a greater proportion in ETN+MTX group [42%(10/24) compared to 27%(4/15) in MTX-TT]. MCR remained unchanged up to week48 but improved with treatment by week 96 to 45%(27/60). MCR rates did not converge between the 2 treatment groups at week 96 (ETN+MTX 55%; MTX-TT 38%).

Conclusion

First-line ETN+MTX is associated with higher rates of stringent remission from week 12 compared to MTX-TT, with improvement gradually over time with both strategies. Significantly higher proportion of patients treated with first line ETN+MTX compared to MTX-TT achieved Boolean and MCR. Early TNFi treatment associates with more complete and better cumulative disease activity profile. Patients not meeting MCR early following treat-to-target approach should be considered for more aggressive treatment strategies.

Disclosure

R. Shukla: None. D. Plant: None. P. Emery: None. M.H. Buch: None.
P138 Inequity in Clinical Commissioning Group funding across England for high-cost biologic drugs in rheumatoid arthritis
Authors: Buckeldee Olivia , Khanna Rajakshi , Snell Laura , Attipoe Laura
Published: April 2023

Background/Aims

Biologic, and targeted, disease-modifying antirheumatic drugs (bDMARDs/tDMARDs) are recommended for patients in England with high disease activity score rheumatoid arthritis (HDAS-RA) who do not respond to two or more conventional synthetic DMARDs. To prescribe bDMARDs/tDMARDs in England, prescribers must apply for funding via their local clinical commissioning group (CCG). The project aim was to review whether CCGs across England had defined high cost drugs pathways for bDMARDs/tDMARDs use in HDAS-RA and if so, what this pathway looked like regarding drug choice, order of availability, and ability to prescribe as monotherapy.

Methods

We submitted a freedom of information (FOI) request in October 2021 to all CCGs within England to obtain their high cost drug pathway for bDMARDs/tDMARDs use in HDAS-RA. We then manually reviewed the pathways to determine whether the CCG specified an order of drug prescribing. Data was also gathered on whether CCGs allowed abatacept (ABT), rituximab (RTX), and golimumab (GOL) to be prescribed as monotherapy.

Results

All 107 CCGs in England responded to the FOI request. 69 out of 107 CCGs (65%) had a pathway for bDMARDs/tDMARDs prescribing. 60 out of 69 CCGs (87%) specified an order for drug prescribing in RA. Within their pathways, CCGs generally fell into 3 prescribing preferences. Table 1 summarises these pathway recommendations. 39 (57%), 59 (86%), and 6 (9%) CCGs allowed ABT/RTX/GOL to be prescribed as monotherapy respectively. RTX monotherapy was specifically allowed outside of special indications such as cancer, interstitial lung disease and multiple sclerosis.

Conclusion

These findings show there is significant variation across England regarding which bDMARDs/tDMARDs patients can receive for HDAS-RA resulting in a postcode lottery. Several studies support the use of ABT/RTX/GOL as monotherapy and registry data shows that 30-40% of RA patients are administered ABT/RTX/GOL as monotherapy for methotrexate intolerance/contraindication. Lack of NICE appraisal, however, means some CCGs mandate individual funding requests for monotherapy prescribing. We would like to use these results to help negotiate equitable access to bDMARDs/tDMARDs nationwide.

Disclosure

O. Buckeldee: None. R. Khanna: None. L. Snell: None. L. Attipoe: None.
P143 Depression modifies the effect of Rheumatoid on Overall Mortality among Females
Authors: Banerjee Sri
Published: April 2023

Background/Aims

Depression is a mental health condition that affects many individuals. When compounded by an autoimmune condition like rheumatoid arthritis, there can be harmful consequences. In this article, we explored if depression modified the connection between rheumatoid arthritis (RA) and overall mortality.

Methods

The study was conducted on participants aged 20 years or older living in the United States. We assessed RA status by using the arthritis question in the NHANES survey for the years 1999 to 2010 with mortality follow-up. We determined depression by Patient Health Questionnaire (PHQ-9). Prospective analysis was performed using complex samples Cox regression with adjustment for known confounders to determine the relationship of RA and mortality, and how depression has an overall relationship in females.

Results

The mean follow-up was 9.1 years. For all-cause mortality, the overall unadjusted hazard ratio (HR) of rheumatoid arthritis to no rheumatoid arthritis was 1.94 (95% confidence interval [CI], 1.25-4.01 p < 0.001). Adjusted HR was elevated, 2.13 (CI 0.98-4.62, p > 0.05), among patients with elevated C-reactive protein with RA but closer to 1.0 (1.90 CI 1.21-1.99, p > 0.05) among patients without depression, after controlling for medical and demographic risk factors. Similar patterns did not apply for males.

Conclusion

RA has poorer outcomes especially when they have depression. These patterns exist among females but do affect males in the same way. Screening for depression should be a part of how rheumatologists treat patients.

Disclosure

S. Banerjee: None.
P144 Socioeconomic deprivation is associated with reduced response and lower treatment persistence with anti-TNF therapies in people with rheumatoid arthritis
Authors: Zhao Sizheng Steven , Kearsley-Fleet Lianne , Rogers Kira , Watson Kath , Bosworth Ailsa , Galloway James , Verstappen Suzanne M ,   BSRBR-RA Contributors Group, Humphreys Jenny H , Barton Anne , Hyrich Kimme L
Published: April 2023

Background/Aims

Recent global health crises have highlighted the importance of socioeconomic (SE) inequalities and its influence on health provision and outcomes. The impact of SE deprivation on treatment of rheumatoid arthritis (RA) is understudied in contemporary biologic-treated populations. The aim of this study was to investigate the association between SE deprivation and outcomes of TNF inhibitor (TNFi) treatment.

Methods

Individuals commencing their first TNFi in the BSR Biologics Register for RA from 2001 to 2020 were included. SE deprivation was proxied using the Index of Multiple Deprivation (IMD), which measures relative deprivation of geographic areas. Using the participants' residential postcode, each individual was assigned a relative rank score and categorised into the 20% most deprived, middle 40%, and 40% least deprived; thresholds were chosen because IMD gives greater distinction within the most deprived areas. DAS28, low disease activity (LDA) and EULAR response at 6 months were compared using linear, logistic and ordinal logistic regression models with the 40% least deprived as referent. Risk of drug discontinuation was compared using Cox models. Models were first unadjusted, then adjusted for potential confounders and/or mediators, namely age, gender, baseline DAS28, BMI, HAQ, number of comorbidities, age at diagnosis, ever smoking status and rheumatoid factor status. Multiple imputation was used for missing data.

Results

17,117 individuals were included (mean±SD age 56±12 years, 76% female), of whom 3002 (18%) were in the 20% most, 6999 (41%) in the middle 40%, and 7116 (41%) in the 40% least deprived groups (Table 1). The 20% most deprived group had higher DAS28 at 6 months (beta=0.30, 95%CI 0.22-0.37) and were less likely to achieve LDA (OR 0.76; 0.68-0.84) and EULAR response (OR 0.73; 0.67-0.80) in unadjusted models. They were also more likely to discontinue treatment (HR 1.19; 1.13-1.25). Adjusted estimates were broadly similar (Table 1).

Conclusion

SE deprivation is associated with reduced response to TNFi and increased risk of treatment discontinuation. Estimates were largely unchanged despite adjusting for potential mediators. SE inequality embodies a multitude of factors that can be intervened upon, including behaviours and biases of clinicians or institutes, which should be a focus of future research.

Disclosure

S. Zhao: None. L. Kearsley-Fleet: None. K. Rogers: None. K. Watson: None. A. Bosworth: None. J. Galloway: None. S.M. Verstappen: None. J.H. Humphreys: None. A. Barton: None. K.L. Hyrich: None.
P157 Distinct differences in complement perturbation between scleroderma-related interstitial lung disease with and without emphysema
Authors: Beesley Claire , Cole Alice , Goldman Nina , Barnett Joseph , Abraham David , Denton Christopher , Mageed Rizgar , Ong Voon
Published: April 2023

Background/Aims

Aberrant complement activation is associated with autoimmune diseases including systemic sclerosis (SSc). As a leading cause of death in SSc, interstitial lung disease (ILD) can coexist with emphysema in non-smoking patients, worsening prognosis. It has been suggested that the airway destruction observed in SSc patients may be an exaggerated inflammatory response related to increased complement activation.

Methods

We analysed 10 complement proteins in plasma samples of 16 non-smoking SSc patients with emphysema (SSc-Emp), 8 SSc no-ILD, 8 SSc-ILD patients and 8 healthy controls (HC) (Table.1) selected from 1800 SSc patients under active follow up at our centre. The extent and distribution of emphysema was evaluated on high resolution computed tomography (HRCT) and enzyme-linked immunosorbent assays (ELISA) were performed for C1q, MASP-2, Factor B, Factor Bb, Factor H, C3, C3a, C4, C5, C5a and TCC (terminal complement complex). One-way ANOVA and post-hoc Tukey test were used for analysis.

Results

HRCT confirmed that amongst the emphysema cohort, there was a spectrum of mild to severe destruction including both paraseptal and centrilobular emphysema. All 16 SSc-Emp patients had ILD and 9 of the 16 patients demonstrated perivascular emphysema not previously described in SSc. The SSc-ILD group was characterised by extensive lung fibrosis on CT, mean FVC 71% predicted. Across the four groups, C1q was significantly reduced in the SSc-ILD cohort (SSc-Emp 950±404µg/mL, SSc-ILD 355±116µg/mL, SSc-no ILD 1087±206µg/mL, HC 858±210µg/mL, p= 0.0002). In contrast, the ratio of C3a/C3 was significantly increased in the SSc-ILD group compared with the SSc-Emp group (SSc-ILD 0.12±0.07 vs SSc-Emp 0.06±0.03, p= 0.0283). The ratio of Bb/B was significantly increased in the SSc no-ILD group compared with all other groups (SSc-Emp 1.57±0.80µg/mL, SSc-ILD 1.27±0.56µg/mL, SSc-no ILD 3.86±1.12µg/mL, HC 1.89±0.75µg/mL, p< 0.0001). There was a trend towards an increased ratio of C5a/C5 in SSc-ILD and SSc-Emp compared with HC and reduced MASP2 in the SSc groups compared with HC.

Conclusion

This data demonstrates dysregulated complement levels in three SSc subgroups. Notably, the perturbed C1q and C3a:C3 pathways in SSc-ILD are reversed in SSc-emphysema, supporting complement activation as part of the divergent tissue remodelling responses in these distinct SSc lung phenotypes.

Disclosure

C. Beesley: Grants/research support; Versus Arthritis [grant number 558800]. A. Cole: None. N. Goldman: None. J. Barnett: None. D. Abraham: None. C. Denton: None. R. Mageed: None. V. Ong: None.
P163 Grey matter myelitis is a severe phenotype of myelitis in systemic lupus erythematosus: experience from a tertiary care hospital in south India over a decade
Authors: Baisya Ritasman , Yerram Keerthivardhan , Murthy GSR , Devarasetti Phani K , Rajasekhar Liza
Published: April 2023

Background/Aims

Myelitis is a severe yet rare manifestation of systemic lupus erythematosus (SLE). Literature on lupus myelitis is limited to case reports and series. Birnbaum et al. reported the largest series (n = 22) with two distinct phenotypes based on clinical and imaging findings with mechanistic and therapeutic implications. Further validation of these two subtypes is not reported to date. The objective of the study was to identify distinct phenotypes in lupus myelitis and compare activity and outcomes with the formulation of a prediction model for survival.

Methods

This is a retrospective study. Data of 35 lupus myelitis patients with follow-up were extracted from the lupus registry (n = 1550) in the last 15 years (2007-2022). Grey matter myelitis (GMM) (i.e., flaccidity, hyporeflexia) and white matter myelitis (WMM) (i.e., spasticity, hyperreflexia) were two subtypes. Disease activity was assessed by SLEDAI-2K and outcome by death/recurrence/disability - modified Rankin score (MRS). MRS at discharge and SLEDAI at admission were used as predictors for survival outcomes among subtypes.

Results

Median age at presentation was 24.5 years (12.5-36.5); female-male ratio 32:3. 24 patients presented with GMM and 11 with WMM. GMM had more CNS events (p-0.02), high SLEDAI (p-0.021) and extra CNS involvement (p > 0.05). Anticardiolipin antibodies were increased in WMM (p-0.03). Weibull survival probability plot showed that 25%, 50% & 75% of GMM patients had probability of death within 13, 85, and 376 months from the myelitis episode respectively. The same for WMM was 96, 256, 556 months respectively, implying that GMM has a worse survival outcome. Using linear regression, MRS at discharge and SLEDAI can predict survival status in GMM (R = 0.64, p = 0.04) but not in WMM (R = 0.42, p = 0.46).

Conclusion

Lupus myelitis has two distinct subtypes. GMM is associated with more active disease, poor survival, and significant disability, and its survival status can be predicted by MRS and SLEDAI scores.

Disclosure

R. Baisya: None. K. Yerram: None. G. Murthy: None. P.K. Devarasetti: None. L. Rajasekhar: None.
P167 Overcoming rituximab resistance in autoimmune disease: back to basics
Authors: Shah Kavina , Klein Christian , Cambridge Geraldine , Sen Debajit , Castelino Madhura , Akbar Arne , Isenberg David A , Leandro Maria , Reddy Venkat R
Published: April 2023

Background/Aims

Previous research into B cell biomarkers of poor response to the anti-CD20 drug rituximab in autoimmune disease relates to insufficient B cell depletion. Expansion of memory B cell (MBC) subsets were also associated with poorer response. We investigated whether the relative expression of the target antigen CD20 on B cell subpopulations could also contribute to drug resistance.

Methods

Peripheral blood samples from 6 rituximab naïve (RTX-N) patients with autoimmune rheumatic diseases (active systemic lupus erythematosus and rheumatoid arthritis), 6 patients previously treated with rituximab (RTX-T), and 6 healthy controls (HC) were obtained. B cell subpopulations were defined using the relative expression of IgD and CD27 using flow cytometry.

Results

Patients in the RTX-N group had significantly higher frequency of CD19+CD20- B cells (median=25.9% of total B cells, compared to 1.26% in HC), p = 0.0022. CD19+CD20-B cells were predominantly switched MBC (IgD-CD27+) and double negative (IgDCD27-) MBC cells. All patients in the RTX-T group (median 22 months post-rituximab) had detectable CD19+CD20- B cells (median=52.25% of total B cells), of which the majority were switched MBC (median=4.54%, range 0.23-74%) and DN B cells (median=53.5%, range 11.6-98.1%). Collectively, we noted that the frequency of CD19+CD20- B cells in peripheral circulation was higher in RTX-T>RTX-N>HC.

Conclusion

Our preliminary results have identified greater frequency of CD19+CD20- population of B cells in peripheral blood of patients with autoimmune disease, particularly after treatment with rituximab, suggesting that they evade rituximab. These are predominantly of the switched MBC and DN B cell subpopulations. Given the potential of these cells to contribute to disease activity in autoimmune disease, alternative strategies targeting CD19 may help overcome rituximab resistance.

Disclosure

K. Shah: Grants/research support; Roche Glycart. C. Klein: Corporate appointments; Roche Glycart. Shareholder/stock ownership; Roche. G. Cambridge: None. D. Sen: None. M. Castelino: None. A. Akbar: None. D.A. Isenberg: None. M. Leandro: None. V.R. Reddy: Grants/research support; Roche Glycart, BRC UCLH.