bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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

Abstract

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&lt; 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

Abstract

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 &gt; 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

Abstract

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&gt;RTX-N&gt;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.
P196 The changing role of biopsy and imaging in the diagnosis of giant cell arteritis prior to tocilizumab treatment
Authors: Hutton Lisa M M 
Published: April 2023

Abstract

Background/Aims
Vasculitis has always relied on pattern recognition, biopsy and imaging to secure a diagnosis. Historically, giant cell arteritis diagnosis has relied too heavily on pattern recognition without scrutiny. The current guidelines recommend securing a diagnosis by either temporal artery biopsy (TAB) or imaging. Ultrasound (US) has been given parity with biopsy in European guidelines for cranial giant cell arteritis (cGCA) although in the USA experience is more limited. Large vessel vasculitis (LVV) may not present with cranial symptoms and is diagnosed by axillary US, MRA or preferably PET. The Clyde GCA Fast Track US Pathway was introduced in 2018 and follows EULAR imaging guidelines. In a health board with access to all diagnostic modalities, how is GCA being diagnosed in patients treated with tocilizumab? How is this changing over time?

Methods
46 patients commenced on tocilizumab for GCA since 2017 had their diagnoses examined. Electronic records and US data were used to categorise diagnosis as a result of biopsy, MRA, PET, ultrasound or clinical diagnosis alone. Clinical diagnoses with neither imaging nor biopsy were reviewed in more depth.

Results
There were 37 women and 9 men; 33 cranial GCA and 13 LVV; 9 presenting with a relapsing pattern of disease and 37 with new presentations. Age range 59-91 (mean of 73 years). Only 3 of 46 patients had no additional proof of diagnosis. Diagnosis was secured by biopsy in 16 and imaging in 27 (14 US and 13 PET).

Conclusion
By 2022, cGCA was equally likely to be diagnosed by US as biopsy. The fast track US service provided support for patients, referrers and surgeons to determine if biopsy was needed to secure a diagnosis. Biopsy was most valuable in delayed presentations or if clinical suspicion was high but US negative. PET is the most useful imaging technique for diagnosing LVV; US of axillary arteries was only positive in a few cases and unable to cover the differential diagnosis. MRA was informative but not diagnostic. All GCA diagnoses should be based on good evidence to warrant the potential toxicity of steroids, tocilizumab and any future treatments for relapsing disease.
Disclosure
L.M.M. Hutton: None.
P199 Glucocorticoid taper success after one and two years treatment in the Imperial College Takayasu Arteritis Cohort
Authors: Alapat Ritu , Porter Andrew , Pericleous Charis , Youngstein Taryn A , Maughan Robert , Mason Justin C 
Published: April 2023

Abstract

Background/Aims
The large vessel vasculitis Takayasu arteritis (TA) is initially treated with high dose glucocorticoids (GC) (40-60mg/day), typically with a csDMARD to induce remission. Subsequently, GC doses are tapered to reduce adverse effects. Although current EULAR guidelines tentatively recommend a target GC dose of &lt; 10mg/day after one year of treatment, data describing GC taper patterns in practice is limited. This study describes GC taper success at one and two years and explores associated baseline and follow-up parameters.

Methods
A retrospective analysis of the Imperial College Takayasu Arteritis Cohort (UK) was undertaken; 158 patients with median follow-up 8.4 [5-13.6] yrs. Patients with sufficient data and typical treatment initiation pattern were analysed, commencing either GC monotherapy or GC + csDMARD and no baseline immunosuppression. Primary outcome: GC &lt; 10mg/day after one and two years of treatment. Secondary outcome: patients achieving the same without intensification (addition of a second DMARD or biologic agent). Evaluation of taper failure causes was supported by NIH disease activity scoring. Taper failure and taper success groups were compared for baseline parameters and treatment at 5 years. Data are median [IQR], comparisons non-parametric for continuous variables.

Results
Of 129 TA cases requiring treatment, 80 (62%) satisfied analysis criteria. Overall, 46 (57.5%) and 59 (73.7%) patients met the primary outcome at years one and two respectively. Of these, 43 (93.5%) and 46 (78%) did so without treatment intensification. Taper success was consistent over time, with 43 (94%) year one taper success cases maintaining status at year two. In most cases (90.5%), year two taper failure was due to inadequate treatment response as confirmed by disease activity scoring (Table). Baseline parameters were similar between groups, except ESR which was significantly lower in the taper success group. As expected, initial treatment with GC monotherapy tended to be lower in the taper success group. At year five, GC doses remained higher and biologic usage was greater in taper failure cases suggesting a more refractory disease course (Table).

Conclusion
The EULAR GC taper target was achieved in 57.5% of patients, increasing to 73.7% by two years. Clinical implementation of this target is practical and will aid in the reduction of cumulative GC exposure and identification of patients requiring treatment intensification.
Disclosure
R. Alapat: None. A. Porter: None. C. Pericleous: None. T.A. Youngstein: None. R. Maughan: None. J.C. Mason: None.
E001 Retroperitoneal fibrosis patients need a dedicated multidisciplinary team
Authors: Qian Evelyn , Harris Helen 
Published: April 2023

Abstract

Background/Aims
Retroperitoneal fibrosis is a rare chronic inflammatory fibrosing condition of the retroperitoneal tissues. Inflammation can cause tethering and occlusion of nearby structures, especially the ureters, leading to acute obstruction as well as long-term renal impairment. This condition usually either presents with nonspecific abdominal pain or when the patient is in crisis due to urological obstruction. There is little known about its treatment beyond steroids. A significant proportion of patients are at risk of relapse. We characterised patients with retroperitoneal fibrosis in our heath board to better understand how these patients present and what the unmet needs in their management are.

Methods
Patients were identified by contacting rheumatologists and by searching the urological stent registry from 2019 to 2022. The records were searched for demographics, events around diagnosis, initial treatment, investigations, including imaging reports and pathology, as well as follow up clinic letters detailing any relapses and complications.

Results
We found 22 patients in the health board with idiopathic retroperitoneal fibrosis. Half had sole care under urology. Only 6 received joint care from urology and rheumatology. Demographics of these patients were comparable to literature (mean age 60 (range 43-81 years), female to male ratio (1:2.6), compared to the reported mean age of 55-60 and female to male ratio of 1:2). Diagnosis was usually made by CT scan. The mean incidence of new diagnosis was 2 per year over the last 10 years in a catchment population of 850,000. In 19 patients with treatment information available, 4 never received steroids or immunomodulation therapy. For those that received steroid therapy, doses ranged from 0.2mg/kg to 0.8mg/kg over a range of 1 week to 6 months of maximum dose duration. 73% of patients now have chronic renal dysfunction with eGFR &lt;60ml/min/1.73m2, and 27% with stage 4 renal failure with eGFR &lt;30 ml/min/1.73m2. One of these patients had end stage renal disease and is deceased.

Conclusion
This characterisation study has shown that patients have had heterogenous journeys with their RPF diagnosis and treatment. 73% of these patients have developed chronic renal dysfunction which is dramatically higher than that of the published literature figure of 32%. In order to improve outcomes, there is a need for a standardized approach to diagnosis, treatment and follow up, involving a dedicated multidisciplinary team.
Disclosure
E. Qian: None. H. Harris: None.
E003 Why do rheumatologists request PET-CT scans and what do they show: an audit from a tertiary London Hospital
Authors: Biddle Kathryn , Chaabo Khaldoun 
Published: April 2023

Abstract

Background/Aims
(18F)FDG PET-CT is an imaging tool with utility in the diagnosis of inflammation, infection and malignancy. In rheumatology settings, it is most commonly used for the diagnosis and monitoring of large vessel vasculitis (LVV), sarcoidosis, polymyalgia rheumatica (PMR), IgG-4 disease and myositis. Whilst PET-CT is highly sensitive for the detection of inflammation, concurrent corticosteroid use impairs this. Furthermore, uptake can be non-specific and incidental abnormalities are often reported. Few cohorts have investigated the real-life use of PET-CT including clinical indication, rheumatological and non-rheumatological findings and patient outcomes.

Methods
98 PET-CT scans were requested by the rheumatology department at St Georges NHS Foundation Trust from January 2017 to December 2021. Data including patient demographics, pre-existing rheumatological disease, corticosteroid use and inflammatory marker levels were collected. Indication for PET-CT and PET-CT findings were reviewed.

Results
As summarised in Table 1, PET-CT scans were most commonly requested for the investigation of raised inflammatory markers, poor response to therapy, concerning clinical features, for the characterisation of abnormal imaging findings and for routine monitoring of disease. LVV and malignancy were the most commonly considered differential diagnoses. At the time of PET-CT scan, 59 (60%) patients were taking corticosteroids. 58 of these patients were prescribed prednisolone (dose ranging between 2mg to 80mg, mean dose 19.6mg OD, median dose 15mg OD) In our audit, 39.8% of PET-CT showed active rheumatological disease. 32.6% showed non-rheumatological abnormalities with 2% demonstrating new cancer diagnoses. The detection of incidental non-specific imaging findings commonly led to the request of further diagnostic tests including ultrasound imaging (11 patients) and endoscopy (7 patients).

Conclusion
In conclusion, PET-CT is a useful imaging tool in the diagnosis and monitoring of rheumatological inflammatory conditions. Despite a majority of patients taking corticosteroids at the time of scan, PET-CT remained an effective diagnostic adjunct. A large number of non-rheumatological imaging abnormalities were seen in our cohort; in most cases, the clinical significance was not immediately clear and further investigations were needed. Further guidance is needed to determine the characterisation and management of these incidental findings to avoid unnecessary, costly and sometimes invasive tests.
Disclosure
K. Biddle: None. K. Chaabo: None.
E022 Effect of upadacitinib in a patient with primary Sjogren syndrome: a case report
Authors: Majumder Muhammad Shoaib Momen , Haq Syed Atiqul 
Published: April 2023

Abstract

Background/Aims
Primary Sjogren syndrome (pSS) is a chronic autoimmune multi-system disease characterized by inflammation of exocrine glands, particularly the lacrimal and salivary glands, as well as multiple extra-glandular involvements. Treatment is often challenging, and until now, no disease-modifying anti-rheumatic drugs (DMARDs) have been approved for this condition. There is a lack of data about the efficacy of Janus kinase inhibitors in pSS. Here we report a patient with pSS successfully responding to upadacitinib.

Methods
A 68-year-old woman presented with pain in multiple joints for 16 years with intermittent use of NSAIDs. She had no low back pain and no self or family history of psoriasis or red eye. She denied dry mouth but required frequent water drinking during meals to aid swallowing and occasionally used artificial tears. MTX was started for her two-month articular flare and positive rheumatoid factor (RF). MTX caused severe vomiting and hyponatremia, and she was hospitalized. After the correction of hyponatremia, she was put on tofacitinib. We reevaluated the case when she came to us. She had grade 2-3 tenderness of most peripheral joints and was bedridden. Immunological parameters revealed RF 127 IU/ml (reference value &lt;14), anti SSA antibody 147 U/ml (normal &lt;3.2), anti SSB antibody 149 U/ml (reference value &lt;8) and anti CCP antibody; ANA, anti-ds-DNA Ab were negative. There was no erosion on the X-ray hands. Schirmer's test was positive (3 mm bilaterally). Unstimulated salivary flow after five minutes was 0.04 ml/min (≤0.1 ml/min indicates salivary hypofunction). She fulfilled the 2016 ACR/EULAR classification criteria, and we diagnosed her with primary Sjogren syndrome. Hydroxychloroquine was initiated, but she discontinued it for anorexia. Considering her age, she was switched to upadacitinib, as European Medicines Agency restricted the use of tofacitinib beyond 65 years.

Results
Her EULAR Sjogren Syndrome's Disease Activity Index (ESSDAI) was six at baseline, indicating moderate disease activity. Her joint pain improved significantly within two months with infrequent use of pilocarpine in the sixth month. Six months after treatment with upadacitinib, ESSDAI came down to 2; the Patient's Global Assessment score was 02 and achieved STAR (Sjogren's Tool for Assessing Response) response 7 (STAR responder if score ≥5).

Conclusion
To our knowledge, this is the first case report on the efficacy of upadacitinib in pSS. Further high-quality clinical trials are required to confirm the benefit of upadacitinib in pSS.
Disclosure
M. Momen Majumder: None. S. Haq: None.