bluuebunny/crossref_metadata_2025 huggingface dataset:
Amorphous curcumin-based hydrogels to reduce the incidence of post-surgical intrauterine adhesions
Authors: Zhang Wenya , He Yuxin , Chu Yun , Zhai Yuanxin , Qian Song , Wang Xinhui , Jiang Pengju , Cui Pengfei , Zhang Yin , Wang Jianhao
Published: April 2024

The incidence of intrauterine adhesions (IUA) has increased with the rising utilization of intrauterine surgery. The postoperative physical barrier methods commonly used, such as balloons and other fillers, have limited effectiveness and may even cause further damage to the remaining endometrial tissue. Herein, we developed an injectable thermosensitive hydrogel using Pluronic F127/F68 as pharmaceutical excipients and curcumin as a natural active molecule. The hydrogel effectively addresses solubility and low bioavailability issues associated with curcumin. In vitro, drug release assays revealed that the amorphous curcumin hydrogel promotes dissolution and sustained release of curcumin. In vitro experiments reveal high biocompatibility of the hydrogel and its ability to enhance vascular formation while inhibiting the expression of fibrotic factor TGF-β1. To assess the effectiveness of preventing IUAs, in vivo experiments were conducted using IUA rats and compared with a class III medical device, a new-crosslinked hyaluronic acid (NCHA) gel. According to the study, curcumin hydrogel is more effective than the NCHA group in improving the regeneration of the endometrium, increasing the blood supply to the endometrium and reducing the abnormal deposition of fibrin, thus preventing IUA more effectively. This study provides a promising strategy for treating and preventing IUA.
OA05 Potential impact of European Medicines Agency measures to minimise risk of serious side effects on those using JAK inhibitors in the UK
Authors: Tian Zixing , Kearsley-fleet Lianne , Galloway James , Watson Kath , Lunt Mark ,   BSRBR-RA Contributors Group, Hyrich Kimme L
Published: April 2024

Background/Aims

Janus kinase inhibitors (JAKi) are effective therapies for rheumatoid arthritis (RA). However, concerns about their safety in certain 'at-risk' populations have resulted in risk minimisation measures introduced by European Medicines Agency (EMA) in January 2023, which limits JAKi prescription to certain patient subgroups unless no suitable alternative is available. The potential impact on current and future JAKi use in the UK is unknown. Using a national cohort study of patients who have already started their first JAKi, this analysis aimed to describe the proportion meeting ≥1 of these criteria and therefore may be impacted by these changes.

Methods

RA patients starting their first-ever JAK inhibitor (tofacitinib, baricitinib, upadacitinib, or filgotinib) therapy in the British Society for Rheumatology RA Biologics Register (BSRBR-RA) before 31st May 2022 (pre-EMA warning) were included. Patients with missing data in any EMA criteria related variables were excluded. Descriptive statistics were used to present patients' characteristics at the start of JAKi. This analysis defined four at-risk criteria assessed at the treatment start: 1) aged ≥65; 2) increased risk of major cardiovascular issues (history of hypertension, hyperlipidaemia, diabetes, ischaemic heart disease, or stroke); 3) current or past smokers; 4) increased risk of cancer (defined as prior cancer). The previous number of distinct biological disease-modifying antirheumatic drugs (bDMARDs) classes was described among those who met the criteria.

Results

A total of 1,362 patients starting their first JAKi were included, most commonly baricitinib (76%), followed by tofacitinib (16%; see Table). The cohort was 78% female, with an average age of 60. Among them, 28% of patients had received ≥3 prior bDMARDs classes. 80% percent of patients (1,090) met ≥1 EMA risk criterion, with the most common individual criterion current/past smoker (54%). Of those who met ≥1 risk criteria, 645 (59%) met ≥1 EMA risk criterion and 29% had already received ≥3 prior bDMARDs classes.

Conclusion

A very high proportion of patients, four-in-five, initiating JAKi in UK before the EMA advisory would have fallen into the ‘high-risk' category for whom prescribing would only be advised if no suitable alternatives were available. Whilst almost a third of them had previously received ≥3 different bDMARDs classes, it’s likely that many of them would have suitable alternatives. These data highlight the enormous impact of the recent licensing updates for JAKi class.

Disclosure

Z. Tian: None. L. Kearsley-fleet: None. J. Galloway: Honoraria; Abbvie, Galapagos, Janssen, Lilly, Novartis, Pfizer, UCB, Vifor. Grants/research support; Abbvie, Galapagos, GSK, Janssen, Pfizer. K. Watson: None. M. Lunt: None. K.L. Hyrich: Honoraria; Abbvie. Grants/research support; Pfizer, BMS.
OA18 Takayasu arteritis mimicking pulmonary embolism: a case series
Authors: Kostich Sophia , Lee Sangoh , Babar Syed , Youngstein Taryn A , Mason Justin , Porter Andrew
Published: April 2024

Background/Aims

Takayasu arteritis (TA) is a rare autoimmune large vessel vasculitis with estimated incidence of 0.7-1.5 per million per annum in Europe. Conversely, pulmonary embolism (PE) is common with incidence estimates of 115 per 100,000 per year. Whilst TA is rare, it can have serious sequelae, including pulmonary vasculitis (PV), resulting in stenoses, aneurysm formation and pulmonary hypertension (PAH). Those with PV may have higher rates of PAH, with estimates around 42%. Early diagnosis ensures early treatment/immunosuppression to minimise arterial injury. Given the rarity of TA with PV, it can be misinterpreted on imaging as a PE. This study aimed to review initial imaging features of TA patients with confirmed PV to identify those who had been incorrectly diagnosed as having a PE. Subsequently, features to differentiate PE and PV were assessed.

Methods

We performed a retrospective analysis of all 158 patients in the Imperial College TA Cohort to identify those with PV. Records and imaging from these patients were reviewed including initial pulmonary vascular imaging.

Results

9 patients with PV were identified, of which 3 had initially been misdiagnosed as having a PE, thereby delaying TA treatment and possibly resulting in accelerated disease course. Table 1 summarises initial presenting features. All patients received anticoagulation for PE; however, their symptoms did not improve. Details of subsequent imaging are included in the table. They each experienced a delay in diagnosis of 7 years, 3 years, and 6 months respectively.

Conclusion

Whilst TA is rare, it is an important diagnosis and not to be missed. Where clinical features are not fitting with a diagnosis of PE, or symptoms are persisting despite management, consider further investigation. Early diagnosis of TA can aid management to try and prevent long term sequelae. Important criteria that should raise suspicion and may suggest TA, some of which were seen in our patient cohort, could include: more insidious onset of symptoms and persistent symptoms despite treatment; normal saturations on observations; normal D-dimer results and a raised ESR/CRP. In the event of clinical doubt for PE, further investigations (ESR) and imaging (MR pulmonary angiogram) should be considered.

Disclosure

S. Kostich: None. S. Lee: None. S. Babar: None. T.A. Youngstein: None. J. Mason: None. A. Porter: None.
OA37 Regional variations in adiposity is a strong predictor of fragility fractures in a large cohort: a cross sectional study
Authors: Amin Hamzah , Khan Aqib , Sultan Zain , Bukhari Marwan
Published: April 2024

Background/Aims

BMI is a core component of fracture risk estimation tools; however, it does not consider the body composition of patients. Emerging research is highlighting that total body fat percentage (TBF%) may be a superior predictor of fracture. Increases in TBF% is thought to be protective of hip fracture while associated with major fragility fractures. However, we have yet to see whether regional variations (abdominal vs hip) in fat deposition is even still a better predictor of fracture.

Methods

Patients were referred to a DEXA scanner in the northwest of England from 2004-2019. A multivariate logistic regression analysis reporting odds ratios was conducted looking at the fat percentage at the left and right hip (FPLH% and FPRH%), as well as abdominally (FPA%), as predictors of fracture. Results were adjusted for smoking, gender, BMI, steroid use and left femoral t-score. Statistical significance was set at p < 0.05 with STATA V12 used as the statistical package.

Results

31,547 patients (5,390 males and 26,156 females) were included in our analysis. The mean age was 64.9 (95% CI 64.8-65.1), BMI 27.1 (95% CI 27.0-27.2), weight 71.1kg (95% CI 70.9-71.3) and height 162cm (95% CI 162.0 cm-162.1cm). 11,875 fractures were reported with 1,375 (11.6%) hip fractures. Table 1 demonstrates the results of our analysis.

Conclusion

The FPLH% was associated with both hip and all major fragility fractures, while FPA% and FPRH% was only associated with major fragility fractures. We would have expected to see a protective effect for hip fractures, considering our patients were clinically overweight; however, this was not observed. Hence, we report in the literature for the first time that FPLH% is predictive for both hip and major fragility fractures even in patients who are clinically overweight. Our approach of considering regional variations in body fat seems to be superior to methods currently used. Hence, we make the recommendation to conduct further research to validate our findings, as well as investigating ways to incorporate such methods into future iterations of fracture risk calculators.

Disclosure

H. Amin: None. A. Khan: None. Z. Sultan: None. M. Bukhari: None.
P005 Early inflammatory arthritis combined nurse and therapist clinic
Authors: Harrison Heather , Allan Rachel
Published: April 2024

Background/Aims

NICE guidelines recommend patients have ongoing access to a multidisciplinary team (MDT). However, ensuring all patients are seen by physiotherapy, podiatry, and occupational therapy (OT), when needed, can be challenging. The aim of the project was for patients to be seen by a therapist, in the first six months of their disease. The plan was to provide treatment and encourage long-term self-management, by providing knowledge of when self-referring to the different therapy services would be beneficial.

Methods

A Nurse and therapist pilot clinic was implemented at the first Disease Modifying Anti-Rheumatic Drugs review appointment. The clinic allowed 15-minutes with a specialist nurse to discuss medication issues and drug counselling. This was followed by 30-minutes with a therapist, to discuss any functional needs and objectively assess any joint issues and to provide treatment. Patients were educated about their condition and signposted to information. Patients were also provided with self-management advice and informed about the role of MDT members. Written or emailed advice was provided. Patients were invited to complete an anonymous questionnaire evaluating their experience.

Results

60 patients were seen in the first three months. Personalised therapy input was given to each patient; however, hand exercises and joint protection advice was given to over 60% of patients. Other therapy input included exercises for other specific joints that were problematic, the provision of wrist splints and relaxation advice. Results of the patient questionnaire showed 98% of patients felt they ‘definitely’ had more information to help manage their arthritis and 100% felt they knew where to go to get more information, if needed. Patients also had a greater understanding of the role of physiotherapy and OT. 88% of patients were confident they would ‘definitely’ know when to ask to be referred to these specialities in the future. Less than 15% of patients required further therapy input following the appointment.

Conclusion

The pilot clinic received excellent patient feedback and fulfilled the aims of providing therapy input, early in patient’s journey. Patients liked the convenience of seeing both the professionals in one visit, felt they had gained more information on their condition and were able to help themselves. Patient’s comments included ‘feeling more supported’ and ‘being able to help myself’. One experienced therapist seeing the patients was more cost effective than separate physiotherapy and OT appointments. The next stage will be to invite all newly diagnosed patients into this clinic as part of an early inflammatory arthritis pathway. We will then audit the impact on therapy referral rates and assess if early intervention reduces the number of therapy referrals long-term, encourages patient self-management and improves patient outcomes.

Disclosure

H. Harrison: None. R. Allan: None.
P006 A new digital front door for existing rheumatology patient queries
Authors: Nadesalingam Kavitha , Short Catherine , Christian Kurt , Helliwell Philip
Published: April 2024

Background/Aims

NICE guidelines recommend people with rheumatological conditions need rapid access to specialist care to manage flares and to advise on medication. With growing demand for NHS services, rheumatology advice lines are coming under pressure. We carried out an audit on our advice line queries over four clinics in summer 2021 with a view to developing a triaging system to improve response time. Over four advice line clinics, there were 44 calls averaging 13 minutes per call. The response time was two to three weeks. 34% of calls were deemed to be inappropriate. Inappropriate calls were considered ones that could be better directed elsewhere.

Methods

In 2022 we started working with DrDoctor, a digital health company to design a digital nurse advice line form to redirect inappropriate calls away from the nurse advice line call backs. This involved designing a digital pathway addressing common inappropriate themes from our audit including redirection of calls to secretaries, patient booking team, prescription management and a digital booking form for phlebotomy appointments. The new digital tool enabled us to expand the service and we used the opportunity to adopt patient assessment tools and educational videos as part of the service. We promoted the digital pathway through patient information leaflets, department website and sent a text with the link to all rheumatology patients. We continued to offer the traditional contact telephone number into the service as well.

Results

The digital nurse advice line went live at the end of July 2023 and after two months the response time has reduced to 1.5- 2 weeks. Since then there have been 529 form submissions from 417 unique patients. 47% of submissions were inappropriate and redirected. 97 patients called to book a blood test and 76 patients opted for the online self-service clinic. 151 patients had a query about their condition. 50% of patient had RA or inflammatory arthritis. 5% AS. 5% SLE. 17% PsA. 23% selected ‘other’ and a free text box captured conditions such as fibromyalgia, osteoporosis, PMR and OA. 26% of patients with rheumatoid arthritis opted to see the educational video on self-examination and 17% watched the educational video on rheumatoid arthritis. Based on 251 submissions that were inappropriate for the advice line, assuming each inappropriate call takes an average of nine minutes based from our previous audit, 39 hours of phone time was saved from avoiding booking inappropriate nurse advice line appointments in two months.

Conclusion

The digital rheumatology advice service is an efficient and effective method of responding to patient queries and can be a source of patient education and self assessment. Informal patient and staff feedback has been positive and we will be collecting formal feedback as the service becomes more established.

Disclosure

K. Nadesalingam: None. C. Short: None. K. Christian: None. P. Helliwell: None.
P023 A case of ANCA-associated vasculitis with possible IgG4-related disease
Authors: Eltahir Hala , Lloyd Mark
Published: April 2024

Background/Aims

IgG4-related disease (IgG4-RD) and granulomatous polyangiitis (GPA) have apparent different pathology. There are infrequent reports of the two conditions occurring simultaneously. We add to the literature by describing a patient who appears to have both conditions.

Methods

A 65-year-old male presented with low back pain radiating to the perineum. His past history included T2DM, CABG and ablation for AF. Initial investigations showed a CRP of 102mg/ml and an eGFR of > 90ml/hr. A CT urogram revealed possible aortitis. A dedicated aortogram showed a cuff of added tissue around the infrarenal aorta and iliac arteries. A whole aortogram showed an increase in the abnormal tissue and detected a left upper lobe cavitating lesion. A PET-CT scan showed activity in the infrarenal aortic tissue, with focal uptake in the aortic arch and right superficial femoral artery. Several pleural based and parenchymal lesions showing moderate increased FDG activity were seen. A CT scan of the sinuses showed multifocal sinonasal mucosal thickening without bony erosions. C-ANCA was positive at 1/40, with raised PR3 of 32U/ml and IgG4 of 2.2g/L. Other immunoglobulin levels were normal and IGRA was negative. A biopsy of the lung lesion showed necrotising granulomatous inflammation and surrounding palisading histocytes, withno vasculitic element. Treatment with prednisolone 40mg daily and methotrexate 15mg weekly was started. A quick symptomatic improvement followed. CRP fell to 14mg/ml within two months. It was discussed in the national IgG4-RD MDT, and the consensus was that he had features of both GPA and IgG4-RD. A follow-up CT scan showed reduction in the volume of para-aortic tissue, with regression of some lesions in the chest, while others increased. However, he remains well with a normal CRP, stable renal function and normal urinalysis. His latest IgG4 level dropped to 0.67 g/L.

Results

The ANCA positivity and lung biopsy findings satisfy classification criteria of GPA. While aortic involvement is not commonly seen in GPA; it is typical of IgG4-RD; however, its diagnostic criteria require a confirmatory biopsy. This is challenging due to the risk of sampling around the aorta and ureters. Our case fulfils criteria for ‘possible’ IgG4-RD. In retrospect, an earlier PET CT scan may have spared the patient several CT scans.

Conclusion

The co-existence of IgG4-RD and ANCA-associated vasculitis may be more common than might be expected. Our case highlights the usefulness of early PET-CT scanning in rheumatic conditions. It is important to check ANCA in suspected IgG4-RD cases. It is possible that future AI programmes may help clinicians better judge the timing of investigations that may be more expensive, invasive or have increased radiation exposure in such complex cases. Finally, the usefulness of a national MDT for IgG4-RD is highlighted. Fortunately, treatment modalities are similar for both conditions.

Disclosure

H. Eltahir: None. M. Lloyd: None.
P044 Janus Kinase Inhibitors-a retrospective study on side effects and discontinuation reasons
Authors: Klein Justus , Alexander Jason , Robertson Lindsay , Hollick Rosemary
Published: April 2024

Background/Aims

In light of drug safety warnings for Janus kinase inhibitors (JAKi), we aimed to evaluate the occurrence of adverse events and identify reasons for discontinuation of JAKi in clinical practice.

Methods

Medical records of all patients prescribed JAKi in NHS Grampian from January 2021 to January 2023 for rheumatic diseases were retrospectively reviewed. Patient demographics, co-morbidities, reasons for treatment discontinuation and occurrence of adverse events (including cardiovascular events) were recorded.

Results

160 patients were prescribed JAKi. 131 (81.8%) patients had rheumatoid arthritis, 16 (10%) psoriatic arthritis, five (3%) axial spondyloarthritis, three (2%) juvenile idiopathic arthritis (in adulthood), 3 (2%) undifferentiated inflammatory arthritis, one (0.6%) granulomatous polyangiitis (GPA), one (0.6%) enteropathic arthritis. Mean duration of treatment was 9.9±12 months with 34.4% on treatment for >12 months. 47.5% discontinued JAKi after an average of 7.0 ± 5.1 months. Patients discontinuing treatment were significantly older than patients who continued treatment 60.1yrs ± 11.0 vs 55.9yrs ± 12.5 respectively, p = 0.03. There were no differences between discontinuing and continuing treatment groups with respect to BMI, smoking, diabetes, cardiovascular disease, hypertension or statin use. Discontinuation rates were 66.7 % tofacitinib, 44.4 % filgotinib and 34.4 % upadacitinib. Discontinuation reasons were inefficacy (37.9 %), headache (9.2 %), infections (9.2 %) and gastrointestinal adverse effects (8.0 %). One patient discontinued JAKi due to an arterial embolism (DVT in the context of undiagnosed patent foramen ovale), three developed new onset hypertension. Common infections leading to discontinuation were urinary tract (37.5 %) and chest (25.0 %), with one case of tuberculosis. No herpes zoster infections led to JAKi discontinuation. In patients who continued treatment infections occurred in 27.1% (30% chest, 21.7%, Covid-19, 13% UTIs, 8.7% herpes zoster 8.7% otitis media). Other adverse events such as fatigue and nausea were reported in < 4 % of all patients. No malignancies were recorded.

Conclusion

Older patients are more likely to discontinue JAKi due to infections. Upadacitinib patients were least likely to discontinue. Treatment inefficacy, urine and chest infections were the commonest reasons for discontinuation.

Disclosure

J. Klein: None. J. Alexander: None. L. Robertson: Other; LR has received funding for conference attendance from UCB. R. Hollick: None.
P058 A service evaluation of rheumatologist-led ultrasound clinics at a tertiary care centre
Authors: Zmuda Alexandra , Manson Jessica , Castelino Madhura
Published: April 2024

Background/Aims

Rheumatologist-led ultrasound (USG) clinics were established at UCLH over 10 years ago with an intention to improve speed of diagnosis and/or execution of treatment plan with the benefit of clinical assessment and diagnostic imaging in one appointment. The benefits for patients may include reduced time taken from work and reduced anxiety. This project aimed to evaluate reasons for referral to this clinic, the outcome of a patient review and the impact of this service.

Methods

Retrospective Health-record data were collected from EPIC using Google forms for patients who had USG of their hands in the specialist clinics for 3 months (Jan - March 2022). Data included patient demographics, clinical data, USG findings, intended change or initiation of treatment, and outcome of the review.

Results

54 patients had been reviewed in the three months. More than half (61%) were referred to help answer a treatment-related question and the remaining were to confirm diagnosis (39%). Most patients referred for diagnosis had their diagnosis confirmed (86%). Majority (62%) also had appropriate follow up and two were discharged; a further six had potential to be discharged at this time. Out of the 33 referred for treatment questions, there were 23(70%) patients who needed no change to their treatment; 15(65%) of these would have potentially been initiated on biologics otherwise. This resulted in potential savings of between £76,497-£107,601 per 6-month (trial of DMARD) period due to drug cost. Table 1 lists potential indirect savings.

Conclusion

This service evaluation found considerable direct and indirect savings that emphasises the need for such specialist service in the cost-strapped NHS. The direct cost savings relate to the drugs that were not required to be initiated, with the majority attributed to the avoidance of biologics. In addition to the indirect cost savings to the NHS , the reduction of risk to the patient of unnecessary immunosuppression remains undefined. As a result of this service evaluation, to enhance potential discharges from this clinic, referring clinicians manage patient expectations at referral and communicatepotential for discharge at referral to the scanning clinician.

Disclosure

A. Zmuda: None. J. Manson: None. M. Castelino: None.
P062 Trust performance in managing inflammatory arthritis over time in England and Wales: a latent class analysis approach
Authors: Yang Zijing , Arumalla Nikita , Russell Mark D , Bechman Katie , Alveyn Edward , Gallagher Sarah , Price Elizabeth , Norton Sam , Galloway James
Published: April 2024

Background/Aims

To evaluate trust-level performance in time to initiation of disease-modifying antirheumatic drug (DMARD) therapy in patients with early inflammatory arthritis (EIA), with identification of change in performance trajectories over time and investigation of trust characteristics associated with this change.

Methods

We included 130 trusts from the UK contributing to the National Early Inflammatory Arthritis Audit (NEIAA) from 2018 to 2020. The primary outcome was days from referral to initiation of DMARD therapy in patients with EIA. Latent class growth mixture models were applied to identify distinct groups of trusts with similar trajectories of performance change over time. We used mixed-effects linear and multinomial logistic regression models to evaluate the association between delay in treatment and trust-level characteristics.

Results

The mean (SD) time to DMARD initiation was 53 (18) days, with an average 0.3-day decrease with each month over time. Four latent trajectories were identified in our cohort, with over 77% of individual trusts showing ongoing improvements in decreasing treatment waiting times. Prior to separating by latent class, time to DMARD initiation was shorter in trusts with higher rheumatology staffing, a local EIA treatment pathway and those with access to musculoskeletal ultrasound. Trusts with more nurses in the rheumatology department were less likely to be in the worse performance group (OR = 0.69 [95%CI 0.49, 0.93]).

Conclusion

In this cohort study, we observed a reduction in treatment waiting time over time. Trusts with better staffed and improved EIA clinical structure are likely to initiate definitive treatment earlier in patients with EIA.

Disclosure

Z. Yang: None. N. Arumalla: None. M.D. Russell: Honoraria; Lilly, Menarini, Galapagos. Grants/research support; NIHR. Other; Pfizer, Janssen, Biogen, and UCB. K. Bechman: Honoraria; Menarini, Galapagos. Grants/research support; NIHR,Versus Arthritis and Pfizer Global Medical Grants for Quality Improvement in Rheumatology Practice. Other; UCB. E. Alveyn: Other; UCB. S. Gallagher: None. E. Price: None. S. Norton: None. J. Galloway: Honoraria; AbbVie, Biovitrum, BMS, Celgene, Chugai, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, Roche, Sanofi, Sobi and UCB.
P079 Denosumab treatment for bone marrow oedema - a case series
Authors: Galloway Megan , Jacobs Alana , Ismajli Mediola
Published: April 2024

Background/Aims

This is a case series of patients treated with a single dose of denosumab to improve bone marrow oedema. Bone marrow oedema can cause significant pain and functional limitations. On MRI imaging, bone marrow oedema is identified as T1 hypointensities and T2 hyperintensities. Denosumab is a human monoclonal antibody that inhibits osteoclast bone absorption via binding to the cytokine RANKL [receptor activator of nuclear factor kappa-B ligand]. The exact aetiology of bone marrow oedema is unknown. It typically occurs in those aged between 40 to 60 years old. Studies have described therapeutic improvement with antiresorptive medications. Bone marrow oedema will generally resolve if left untreated. However, pharmacological treatments can curtail the clinical course.

Methods

This case series has emerged from Chelsea and Westminster hospital. Data was collected over a five year period for seven patients with bone marrow oedema [demonstrated on MRI] that were treated with denosumab. Six of the seven patients had a spontaneous insufficiency fracture associated with the bone marrow oedema on imaging. In our case series, two of the patients had bone marrow oedema in their hips and five in their knees. Denosumab was administered as a single 60mg subcutaneous injection. Response to treatment was ascertained by repeat MRI scan 2-4 months after denosumab treatment as well as patient reported outcomes.

Results

The average age of the patients was 56.4 years [age range 48-68 years]. Five of the patients [71%] reported improved symptoms at the affected site. Four patients [57%] had complete resolution of their bone marrow oedema on imaging with a further patient [14%] having an improved radiological appearance. Visual analogue scale [VAS] scores improved by 50%, although this data was only collected for some of the patients. No side-effects or complications were noted from the treatment. One of the patients who did not improve with denosumab treatment went on to have a total hip replacement due to complete loss of joint space. It is noteworthy that following further investigations, five of the seven patients were diagnosed with osteopenia on dual-energy x-ray absorptiometry [DEXA] scan, one had osteoporosis [and was subsequently commenced on alendronic acid] and one did not attend for their DEXA scan.

Conclusion

This series demonstrates that denosumab is an effective treatment for bone marrow oedema. Denosumab given as a single dose can be considered a safe treatment; there is not the risk of rebound worsening of bone density on treatment cessation that can be seen with prolonged treatment. Denosumab should be offered to patients who are symptomatic from bone marrow oedema to allow for quicker symptom relief and radiological improvement. Our findings are similar to that of a slightly larger case series of fourteen patients by Rolvien et al. published in 2017.

Disclosure

M. Galloway: None. A. Jacobs: None. M. Ismajli: None.
P090 Real-world data on immuno-modulation therapies and body mass index in children and young people with juvenile idiopathic arthritis
Authors: Hartley Karen , Jandial Sharmila , McErlane Flora , Sen Ethan , Sampath Sunil
Published: April 2024

Background/Aims

There is some evidence that children and young people (CYP) with Juvenile Idiopathic Arthritis (JIA) who are overweight/obese have less favourable disease control and treatment outcomes. The aim of this study was to investigate any association between BMI and total number of immune modulation therapies used in CYP with JIA.

Methods

This was a retrospective observational study at a tertiary paediatric rheumatology centre. Cross-sectional data was captured in April 2022 from CYP receiving immunomodulation therapies for JIA. Data on diagnosis, treatments and weight/height at last routine follow-up was included. BMI was calculated for each patient and centile assigned using Royal College of Paediatrics and Child Health electronic BMI charts as follows: BMI ≥85th to 94th centile - overweight, ≥95th centile - obese, as per population monitoring British 1990 growth reference (UK90).

Results

187 CYP were identified and 180 included (seven were excluded due to missing BMI data). Baseline demographic, disease and treatment data are summarised in Table A. 67% were female. Median (interquartile range (IQR)) age in years at diagnosis and follow-up was 4.3 (2.7, 8) and 11.9 (8.5, 14.4) respectively. At follow-up, 41.1% of CYP were either obese or overweight. The median (IQR) number of total immunomodulation therapies per patient according to BMI categories were: under/normal weight 2 (1, 3); overweight 3 (2, 3) and obese 3 (2, 5). The median (IQR) years of follow-up in under/normal weight, overweight and obese groups were 4.77 (2, 8.74); 5.27 (1.86, 7) and 5.5 (3, 9.1) respectively.

Conclusion

CYP that were overweight/obese received more therapies compared to under/normal weight. The high proportion (41%) of CYP in this study who were either overweight or obese is similar to prevalence (44.2%) for children in year six at school in this region. Corticosteroid use and limited physical activity is associated with inadequate control of joint inflammation and increased BMI but this data was not collected and is an important limitation, in addition to cross-sectional and retrospective study design. The overweight/obese group had longer follow-up and may have accumulated more therapies. Future research to evaluate optimal dosing of immunomodulation in CYP with high BMI is warranted.

Disclosure

K. Hartley: Grants/research support; NIHR BRC Internship. S. Jandial: None. F. McErlane: None. E. Sen: None. S. Sampath: None.
P110 Characteristics of Difficult to treat Rheumatoid Arthritis patients in a large District Hospital in the UK
Authors: Oo Kyaw Naing , Memon Murk , Sharma Poonam , Dahiya Sandeep
Published: April 2024

Background/Aims

Difficult-to-treat rheumatoid arthritis (D2T RA) has a notably higher impact on a patient’s quality of life and is a significant cost and service pressure to the health care provision in comparison to non-D2T RA. The primary aim of this study is to delineate the major contributing factors and characteristics of patients leading to a diagnosis of D2T RA, using the criteria established by the European League Against Rheumatism (EULAR).

Methods

A retrospective study was conducted within the Rheumatology department in a large district general hospital, with a catchment population of over 700,000 people. A cohort of 722 patients, all of which were on biologic Disease Modifying Anti-Rheumatic Medications (DMARDs) was selected. In this study, we present our findings for the first 95 consecutive patients.

Results

Of the selected 95 patients, 13% met the EULAR criteria for D2T RA. The key characteristics within this subset include 75% being sero-positive (both Rheumatoid factor and anti-cyclic citrullinated peptide), 66% being categorized as obese, and 42% having concurrent fibromyalgia and osteoarthritis. Among these 13% D2T RA patients, 25% demonstrated a high disease activity index and 75% showed moderate severity. All these patients had been started on at least two conventional DMARDs including methotrexate before escalating to more advanced treatments in line with NICE guidelines. From the subgroup of high disease activity D2T RA patients, 67% had tried at least three types of biologic or targeted synthetic DMARDs (b/ts DMARDs), and 33% had been trialled on four different types of b/ts DMARDs. Similarly, out of the medium severity D2T RA subgroup, 45% had tried three and four DMARDs respectively and 10% had been given five biologic or synthetic DMARDs.

Conclusion

The major contributing factors leading to D2T RA within this study population appear to be seropositivity for both RF and anti-CCP, obesity, and the presence of comorbidities like fibromyalgia and osteoarthritis. The intertwined relationship between these factors emphasizes the need for a comprehensive and individualized approach to managing patients with D2T RA. Although this cohort is larger than the previous studies, the sample size is relatively small. We aim to look at the remaining 627 patients to identify trends and modifiable risk factors that could help prevent the future development of D2T RA.

Disclosure

K. Oo: None. M. Memon: None. P. Sharma: None. S. Dahiya: None.
P140 IgG Autoantibodies with Increased Affinity for Epithelial Cells in Severe Systemic Sclerosis
Authors: Moezinia Carine , Wong Valerie , Watson James , Nagib Lydia , Garces Sandra Lopez , Lopez Henry , Martin George , Zhang Siyu , Abdi Bahja Ahmed , Denton Christopher , Abraham David , Stratton Richard J
Published: April 2024

Background/Aims

In health IgG immunoglobulins form a network through interaction with cell surface proteins and controlled by regulatory cells, whereas in autoimmune diseases IgG responses become skewed towards higher affinity and potentially damaging responses against self-antigens. Moreover, recent studies have demonstrated activation of the epithelial layer of skin in systemic sclerosis (SSc), implicating keratinocytes as a target of the autoimmune process. We investigated the presence of plasma IgG autoantibodies directed against keratinocytes and sought correlation with clinical parameters in well-characterized patients.

Methods

Diffuse SSc (dcSSc), limited SSc (lcSSc) and healthy control (HC) plasma samples (each n = 30), were assayed in an anti-epithelial cell antibody assay (AEpCA), using fixed keratinocytes to evaluate binding of IgG . Clinical characteristics of patients with positive versus negative AEpCA were compared. The capacity for SSc IgG to activate epithelial cells was assessed using keratinocytes in vitro.

Results

Preliminary serial dilution assay of SSc and HC plasma (n = 10) showed enhanced affinity of SSc IgG for keratinocytes (ANOVA p < 0.001 for overall effect SSc vs HC IgG p < 0.0048 for dose effect)(Figure 1A). Dilution of 1/80 gave optimal differential binding in the AEpCA assay (corrected p < 0.027 for SSc vs HC at 1/80). Further HC, dcSSc, and lcSSc plasma samples (each n = 30) were screened, demonstrating increased AEpCA titre in SSc (Figure 1B) (Kruskall-Wallace test p < 0.014 for lcSSc vs HC, p < 0.041 for dcSSc vs HC). SSc patients with positive AEpCA had higher skin scores (mRSS) (AEPCA neg 5(0-24); AEpCA pos 9(0-40) p < 0.0032), higher frequency of ATA antibody (AEpCA neg ATA pos 6/30; AEpCA pos ATA pos 13/30, chi squared p = 0.052) more interstitial lung disease (AEPCA neg 7/30, AEpCA pos 13/30, p NS)(Figure 1C) and trend towards higher use of immunosuppression. SSc but not HC IgG activated keratinocytes in vitro, triggering IL-1α release.

Conclusion

In this study, we have shown evidence of IgG autoantibodies with increased affinity for keratinocytes in the plasma of SSc patients. Positive testing for the AEpCA was associated with more severe skin disease and lung involvement. The perturbed IgG network in such patients could be activating through common epithelial cells antigens in the skin and lung.

Disclosure

C. Moezinia: None. V. Wong: None. J. Watson: None. L. Nagib: None. S. Lopez Garces: None. H. Lopez: None. G. Martin: None. S. Zhang: None. B. Ahmed Abdi: None. C. Denton: None. D. Abraham: None. R.J. Stratton: None.
P141 The Roles and Therapeutic Implications of Macrophages in Inducing Calcinosis Via Activin-A Pathway and CD206 Expression in Patients with Systemic Sclerosis
Authors: Liang Kaifeng , Lopez Garces Sandra , Searle Tamara , Lopez Henry , Martin George , Denton Christopher , Abraham David , Stratton Richard J
Published: April 2024

Background/Aims

Calcinosis may result from localised trans-differentiation of tissue resident stem cells in the subcutaneous layer of affected skin in systemic sclerosis (SSc), as a severe disabling manifestation linked to ischaemia and local trauma. Polarised macrophages synergistically promote osteogenesis: M1 macrophages recruit mesenchymal stem cells leading to osteogenic differentiation, while M2 are responsible for osteoblast formation. Previous studies have implicated two pathways-Activin-A signalling and CD206 expression by macrophages - in heterotopic osteogenesis. We investigated the pathogenesis of calcinosis through macrophages, using a novel tissue culture model created by stimulation of adipose derived mesenchymal stem cells (ASCs) with SSc macrophages and explored the relevance of the Activin-A pathway.

Methods

Activin-A was measured by ELISA in diffuse cutaneous systemic sclerosis (dcSSc) patients' (n = 72), and healthy control (HC) plasma samples (n = 42). Macrophages were derived from peripheral blood monocytes of dcSSc patients (n = 4) and cultured under basal and BzATP-stimulated conditions. dcSSc macrophages were maintained in co-culture with ASCs in osteogenic media ±anti-activin-A neutralising antibody (anti-AA). Osteogenesis was assessed using Alizarin Red.

Results

Activin-A was increased in dcSSc patients’ plasma when compared to HC, most notably in anti-centromere antibody (ACA) subgroup (plasma activin-A 521±199pg/ml vs 255 ± 170pg/ml [p = 0.000065]) (Figure 1A). Moreover, there was synthesis of Activin A by SSc macrophages, enhanced by stimulation with BzATP (0.1µM) (basal Activin A 3.3 (0-14.5), BzATP stimulated 21.7 (7.7-418) pg/ml p NS) (Figure 1B). In co-cultures, the addition of SSc macrophages to ASCs led to significantly enhanced synthesis of Activin A, which was reduced by the addition of anti-AA (ASC monoculture 987+/-87, SSc macrophages+AScs 1599+/- 122, p < 0.0065, SSc macrophages+ASCs+anti-AA 1034+/-108 pg/ml, p < 0.013) (Figure 1C). Moreover, adding SSc macrophages to ASC cultures significantly enhanced calcinosis, as measured by Alizarin red stain, but anti-AA did not fully supress the Alizarin staining (ASC: 0.5, 0.4-0.7; ASC+M: 13.0, 5.8-17.2 p = 0.0022; ASC+M+anti-AA p NS median, IQR, red pixels per field) (Figure1D).

Conclusion

Elevated plasma Activin-A, most notable in ACA subgroup, is consistent with systemic upregulation of the Activin-A pathway in SSc. The interaction of activated macrophages with ASCs represents a potential model for calcinosis. Targeting Activin-A might benefit in this severe complication.

Disclosure

K. Liang: None. S. Lopez Garces: None. T. Searle: None. H. Lopez: Corporate appointments; CEO of Murigenics. G. Martin: Corporate appointments; Senior Scientific Officer Riptide. C. Denton: None. D. Abraham: None. R.J. Stratton: None.
P150 Diagnostic utility of anti-cN1A autoantibody testing in sporadic inclusion body myositis
Authors: Al-Attar Mariam , Khoo Thomas , Lilleker James B , Chinoy Hector
Published: April 2024

Background/Aims

Sporadic inclusion body myositis (sIBM) is the most common acquired myopathy in patients aged over 50 years. Diagnostic criteria encompass clinical, biochemical, and myopathological features. Certain myopathological features possess high specificity but low sensitivity; reliance on such findings may lead to delayed or misdiagnoses. The discovery of autoantibodies against cytosolic 5'-Nucleotidase 1A (cN1A) in sIBM patients suggests an autoimmune component in pathogenesis, but the inclusion of this autoantibody in diagnostic criteria remains uncertain. Additionally, optimal testing methodology has not been established, with varying techniques (e.g., ELISA/line-blot) in use. We assessed antibody profiles in an sIBM cohort and reviewed diagnoses in anti-cN1A positive patients.

Methods

This study was based at the Northern Care Alliance NHS Foundation Trust which hosts a tertiary neuromuscular referral service for the North-West of England. Data sources included myositis clinic and immunology results databases. All patients tested using a validated myositis line-blot immunoassay (EUROLINE 16 Antigen et cN1A [EUROIMMUN]) November 2021-April 2023 were included. Diagnoses of all tested patients were identified through case-note review. Sensitivity and specificity metrics were calculated based on diagnosis and anti-cN1A antibody status.

Results

The total number of patients tested for anti-cN1A was 495. Of these, 10 patients had a diagnosis of sIBM. The true-positive and false-negative rates were both 50% (n = 5 each). Of the 485 patients who did not have sIBM, true-negativity was 97.52% (n = 473) and false-positivity 2.47% (n = 12). Overall, anti-cN1A had a sensitivity of 50%, specificity of 97.52%, positive predictive value of 29.41% and negative predictive value of 98.95% for sIBM (Table 1). Patients with a false-positive anti-cN1A antibody had diagnoses of: primary Raynaud’s (n = 5); undifferentiated CTD (n = 3); systemic sclerosis (n = 2); non-sIBM myositis (n = 2).

Conclusion

Anti-cN1A detected using the EUROLINE 16 Antigen assay has high specificity but lacks sensitivity for sIBM, consistent with previous literature. These findings suggest that this assay performs similarly to other cN1A detection methodologies and has utility in confirming the diagnosis of sIBM where there is clinical suspicion. Further real-world analysis of antibody data in larger cohorts is required to clarify the role of serological testing in sIBM diagnostic criteria, to improve diagnostic delays and misclassifications.

Disclosure

M. Al-Attar: None. T. Khoo: None. J.B. Lilleker: None. H. Chinoy: None.
P156 Type I interferon is raised across connective tissue diseases and is associated with haematological abnormalities and specific autoantibody profiles
Authors: Madenidou Anastasia-Vasiliki , Rice Gillian I , Dyball Sarah , Parker Benjamin , Briggs Tracy A , Bruce Ian N
Published: April 2024

Background/Aims

The overlapping clinical and serological features among connective tissue diseases (CTDs) suggest a shared molecular aetiology. A molecular taxonomy of CTDs offers new opportunities in clinical trial design, which can potentially be translated into targeted treatment. In a previous study of 164 patients, we identified a type I interferon (IFN) positive subgroup within an unselected CTD cohort associated with specific clinical and serological features. Here, we aim to investigate the relationship between type I IFN and the clinical and immunological phenotype in a larger CTD cohort and determine whether a distinct subpopulation of patients can be identified.

Methods

Adult patients with at least 1 CTD clinical feature and CTD-related autoantibody were recruited from five rheumatology centres in North West England into the Lupus Extended Autoimmune Phenotype (LEAP) cohort. A 24-gene interferon-stimulated gene (ISG) score was calculated using NanoString as described by Neasens et al. 2022.

Results

Most patients had lupus (36%). 160 of 344 (46.5%) patients had a positive ISG score across all CTDs with 64/125 (51%) of lupus patients (Fig.1). Patients with positive ISG score were younger and had longer disease duration (p < 0.005 for both). There were no differences in mucocutaneous or internal organ involvement between the ISG subgroups. The ISG-positive group had significantly increased frequency of specific autoantibodies (anti-Smith, anti-Chromatin, anti-RNP, anti-Ro) and Rheumatoid Factor, and haematological abnormalities (lower haemoglobin, and lower total white cell and neutrophil counts) in an adjusted model including the CTD subtype.

Conclusion

In CTD patients, IFN type I positivity was identified across a subset of patients of all CTDs and is associated with specific autoantibodies and haematological parameters; these results support the findings of our previous smaller study. The identification of an IFN I-positive subgroup within an unselected CTD regardless of clinical diagnosis supports a molecular-based approach to treatment.

Disclosure

A. Madenidou: Grants/research support; Janssen and UCB. G.I. Rice: None. S. Dyball: Grants/research support; UCB, Novartis,Eli Lilly. B. Parker: Honoraria; Fresenius-Kabi and AbbVie. Member of speakers’ bureau; Eli Lilly and Roche. Grants/research support; Genzyme/Sanofi and GlaxoSmithKline. T.A. Briggs: Grants/research support; Janssen. I.N. Bruce: Consultancies; AstraZeneca, Eli Lilly, GlaxoSmithKline, Merck Serono and UCB. Member of speakers’ bureau; AstraZeneca, GlaxoSmithKline and UCB. Grants/research support; Genzyme/Sanofi, GlaxoSmithKline, Roche, Novartis, Janssen and UCB.