bluuebunny/crossref_metadata_2025_split huggingface dataset:
OA14b Etanercept originator versus its biosimilar (SB4) for the treatment of rheumatoid arthritis. Are they truly similar?
Authors: Rokad Aasiyah , Kearsley-Fleet Lianne , Watson Kath , Lunt Mark ,   BSRBR-RA, Hyrich Kimme L 
Published: April 2022

Abstract

Background/Aims
Etanercept biosimilar SB4 (ETN-B) showed comparable efficacy to its biologic originator (ETN-O) among biologic-naïve patients with rheumatoid arthritis (RA) in randomised controlled trials. Subsequently, a nationwide guideline in the United Kingdom (UK) obligated the prescription of biosimilars in 2016, resulting in significant cost-savings to the NHS. However, real-world evidence comparing ETN-O and ETN-B is limited. This analysis aims to compare the effectiveness of ETN-O versus ETN-B amongst biologic-naïve patients with RA treated in routine clinical practice in the UK.

Methods
The British Society for Rheumatology Biologics Register for RA (BSRBR-RA) is a prospective observational cohort study. This analysis included patients starting their first biologic (ETN-O or ETN-B), recruited since 2010, with at least one follow-up. Baseline data are collected at start of therapy, including patient demographics and disease activity. Follow-up data are collected six monthly for the first three years and annually thereafter, including changes in disease activity and anti-rheumatic therapy. Key outcomes assessed were change in Disease Activity Score for 28-joints (DAS28), DAS28 remission, EULAR treatment response, change in Health Assessment Questionnaire (HAQ), and minimal clinically important difference (MCID) in HAQ. Drug retention was explored using Kaplan-Meier and Cox-regression analyses, along with reasons for treatment withdrawal. Multiple imputation was used to account for missing data and confounding by indication was accounted for using propensity-decile adjustment.

Results
This analysis included 1927 patients with RA starting their first biologic therapy: 996 (52%) ETN-O and 931 (48%) ETN-B. At six-months, change in DAS28 and HAQ were similar between therapies (Table). There were no differences in key imputed propensity adjusted outcomes (odds ratio [95% confidence interval]): DAS28 remission: 0.90 (0.7-1.1, p = 0.3); MCID in HAQ: 0.86 (0.7-1.1, p = 0.3) and EULAR treatment response: 0.96 (0.8-1.2, p = 0.8). One-year retention rates were 69% (95% CI: 66-72) for ETN-O and 70% (95% CI: 67-73) for ETN-B and the main reasons for treatment withdrawal were adverse events and ineffectiveness for both drugs.

Conclusion
This analysis is the first to our knowledge to show similar outcomes amongst biologic-naïve patients with RA treated with either ETN-O or ETN-B using real-world data, which brings further evidence for similarity between the drugs.

Disclosure
A. Rokad: None. L. Kearsley-Fleet: None. K. Watson: None. M. Lunt: None. K.L. Hyrich: Honoraria; Abbvie. Grants/research support; Pfizer, BMS.
OA15 Drivers of change in four and two component disease activity scores after etanercept treatment, in a multi-centre cohort of patients with established rheumatoid arthritis
Authors: Stadler Michael , Ling Stephanie , Nair Nisha ,   BRAGGSS, Isaacs John , Hyrich Kimme , Morgan Ann , Wilson Gerry , Plant Darren , Bowes John , Barton Anne 
Published: April 2022

Abstract

Background/Aims
Treatment response in RA is measured by different disease activity scores (DAS28). The widely used 4 component (4C) DAS28 does not always correlate with synovitis, and a new 2 component version (2C) DAS28 has been developed to address this problem. Here, we use multivariable linear regression models to identify drives of change (Δ) in 4C and 2C DAS28 after 3 months on the anti-TNF drug etanercept (ETN).

Methods
Using data from the Biologics in RA Genetics and Genomics Study Syndicate (BRAGGSS), we identified patients treated with originator or biosimilar ETN (N = 773). Differences between the follow-up (FU) and baseline (BL) DAS28, adjusted for baseline, serve as outcome variables. Multiple imputation by chained equations was used to impute missing data, and models were internally validated via bootstrapping. Table 1 shows the baseline statistics, and model parameters for the included covariates.

Results
We found that 15.8% (95% CI: 11 - 20.6%) of the variance in Δ4C was explained by the baseline DAS28, compared to 26.3% (95% CI: 20.9 - 31.7%) for the Δ2C. Age of onset, HAQ score and concurrent DMARD treatment were significantly associated with both ΔDAS28 scores. Δ4C-DAS28 was additionally associated with first biologic use, seropositivity for either rheumatoid factor or anti-citrullinated peptide antibodies, and the Hospital Anxiety and Depression Scale-Anxiety score. The only additional predictor significantly associated with Δ2C-DAS28 was weight. After adjusting for baseline DAS28, the additional clinical covariates only explained 7.6% (IQR: 7.3 - 7.8%), and 2.3% (IQR: 2.0 - 2.6%) of the variance for the 4C- and 2C-DAS28, respectively.

Conclusion
ΔDAS28 is heavily influenced by the baseline DAS28, and additional clinical covariates explain little to none of the additional variance. Notably, known factors associated with treatment response, such as seropositivity and previous unsuccessful treatments, were only significant for the 4C-DAS28. This suggests that the 4C DAS and 2C DAS capture different aspects of RA disease progression. Further association studies are required to find other reliable predictors for ΔDAS28, which may include biological markers of response. Significant covariates identified here should be considered as potential confounding factors.

Disclosure
M. Stadler: None. S. Ling: None. N. Nair: None. J. Isaacs: None. K. Hyrich: None. A. Morgan: None. G. Wilson: None. D. Plant: None. J. Bowes: None. A. Barton: None.
OA24 Predicting drug immunogenicity to tumour necrosis factor inhibitors in patients with rheumatoid arthritis
Authors: Alshehri Mohammed , Nair Nisha , Yap Chuan Fu ,   BRAGGSS, Isaacs John D , Hyrich Kimme , Morgan Ann W , Wilson Anthony G , Barton Anne , Plant Darren 
Published: April 2022

Abstract

Background/Aims
Rheumatoid arthritis (RA) is a chronic immune-mediated inflammatory disease that irreversibly damages synovial joints. Tumour necrosis factor inhibitors (TNFi) may be prescribed for patients with moderate to severe RA. However, approximately 40% of patients do not respond well to TNFi, with a lack of effectiveness underpinned by immunogenicity (development of anti-drug antibodies) in some patients. A recent well-powered study by Sazonovs et al. (2020) reported a strong genetic association between the HLA-DQA1 locus and immunogenicity to TNFi in a cohort of Crohn's disease patients treated with either infliximab or adalimumab. The current study aimed to investigate the association between HLA alleles, primarily HLA-DQA1, and immunogenicity to adalimumab in RA patients.

Methods
Anti-adalimumab antibody titres were measured using radioimmunoassay in serum samples from RA patients following six months of treatment. Genetic datasets were generated using the Illumina OmniExpress genotyping array and, following standard quality control filtering, variants were imputed using SNP2HLA statistical software. Following imputation, filtering was performed to exclude variants in linkage disequilibrium or with low minor allele frequency. Logistic regression models were developed to explore the association between HLA alleles and amino acids and immunogenicity (all models were adjusted for sex). Amino acid positions of interest were annotated using P2Rank; a ligand binding site prediction tool.

Results
A total of 171 HLA alleles and 339 amino acid positions were analysed in 226 RA patients. The strongest association observed between HLA alleles and immunogenicity was for HLA-DQB1*02 (coefficient = 0.87; 95% CI, 0.31-1.43; p value = 2.10E-3), followed by HLA-DQA1*05 (coefficient = 0.91; 95% CI, 0.29-1.53; p value = 3.95E-3). The strongest associated amino acid positions were amino acids 66 and 67 within the ligand binding domain of the HLA-DQB1 protein.

Conclusion
In keeping with previous findings in Crohn's disease, variants within HLA-DQ molecules confer the strongest evidence for immunogenicity risk in RA patients receiving adalimumab. RA patients carrying these variants could be redirected to receive etanercept, an effective alternative to monoclonal antibodies that is not immunogenic. Further well-powered studies in RA are now warranted to replicate these findings.

Disclosure
M. Alshehri: None. N. Nair: None. C. Yap: None. J.D. Isaacs: None. K. Hyrich: Honoraria; Abbvie. A.W. Morgan: None. A.G. Wilson: None. A. Barton: None. D. Plant: None.
OA31 Youth-led development of an animated film to aid recruitment to a national youth advisory group for adolescent and young adult rheumatology
Authors: Lunt Laura E , Purvis Morgan , Gnanenthiran Suruthi , Zing Pelin , McDonagh Janet E , Rheum Your ,   a national advisory group of BANNAR
Published: April 2022

Abstract

Background/Aims
Your Rheum is a national youth advisory group for adolescent and young adult rheumatology, to ensure meaningful involvement of young people at all stages of research. It was established in 2016 as a result of nationwide research, which reported that young people with rheumatic conditions wanted to be actively involved and had clear opinions of how they wanted to be involved and the priorities for such research. Young people ageing-out of the group remains challenging in view of the national nature of the group and was further compounded by the impact of the COVID-19 pandemic, which prevented the face-to-face meetings of the group. The aim of this project was to develop a short animation detailing what Your Rheum is about to encourage young people to join.

Methods
Content for the animation was gathered at a virtual Your Rheum meeting and via an online survey sent to members. A smaller group of members (n = 4) then worked with the Your Rheum facilitator and a national animation company, More Than Minutes, to create a script, storyboard, to choose imagery, colour schemes and discuss a voiceover. The animation was subsequently revised in the light of feedback from the young people.

Results
Key areas of content included: who can get involved in Your Rheum and membership; the different ways the group works with researchers for example group virtual and face-to-face activities, individual online activities; examples of different projects and topics of research discussed; why it is important to involve young people in research; how to contact the Your Rheum team. It was important to ensure the animation imagery was bright, fun and highlighted diversity. Language used in the film had to be clear and simple to understand, to enable young people from the age of 11 years upwards to relate. Subtitles on the video were also an important feature. The animation was successfully launched in September 2021 - [https://youtu.be/Y8OqmEJZ9Eo]

Conclusion
It is important to harness the experience and opinions of young people at all stages of research including recruitment strategies and dissemination, as this can result in resources that truly resonant with this age group.

Disclosure
L.E. Lunt: None. M. Purvis: None. S. Gnanenthiran: None. P. Zing: None. J.E. McDonagh: Consultancies; Consultancy fees from Pfizer (2018) and CSL-Behring (2021).
P050 Rapidly worsening subcutaneous oedema in a young boy: a case of juvenile dermatomyositis
Authors: Janagan Shalini , Udeshika W. A. E , Samarasinghe Pasindu M , Jagoda Jayatri D 
Published: April 2022

Abstract

Background/Aims
Juvenile onset dermatomyositis (JDM) is a rare disease with an incidence of 2-4 per million. The presentation includes skin manifestations of heliotrope rash, Gottron's papules, nail fold changes, bilateral peri-orbital or upper eyelid edema and focal mild facial swelling with muscle weakness. Widespread and generalized subcutaneous oedema is a rare presentation in JDM.

Methods
A 4-year-old previously healthy boy presented to a tertiary care hospital in Sri Lanka with generalized rash involving the face, limbs and trunk for seven days associated with facial puffiness and hair loss. He also complained of generalized myalgia and irritability and refused to walk. He did not have dysphagia, dysphonia or shortness of breath. He had a prodromal febrile illness two weeks back that had been treated as a viral fever. He had evidence of palatal ulcers, chelitis, malar rash, erythema of eyelids, eyelid swelling and necrotic vasculitic lesions in peripheries. He had tenderness over his thighs with muscle power being MRC grade 3/5 in the proximal muscles of his lower limbs. Arm and neck flexors’ power was normal.

Results
His ESR was raised at 35 mm/hour and CRP was normal. His CPK was 2726 U/l, AST was raised at 931 U/l, ALT was 511 U/l and albumin was 33 g/l. His ANA, dsDNA and ENA panel was negative. A myositis immunoblot could not be done due to financial constraints. An EMG showed evidence of myositis in his proximal muscles. He fulfilled the criteria for juvenile dermatomyositis based on Bohan and Peter’s criteria. He was treated with high dose steroids, dexamethasone 2 mg 6 hourly. While receiving steroids he deteriorated with worsening subcutaneous oedema of face and neck with high fever spikes. The oedema progressed to involve his whole body. His muscle power deteriorated with involvement of his arms. A venogram ruled out any obstructive venous disease. A CT CAP ruled out any underlying malignancy. His 2D echo revealed normal heart function. He was converted to IV Methylprednisolone 30 mg/kg and was started on plasmapharesis. He improved after the 3rd cycle and was started on cyclophosphamide infusions. He received six cyclophosphamide pulses with a tapering course of steroids. He remains controlled in his disease with no new muscle weakness or skin manifestations. However, he remains steroid dependent and is awaiting treatment with Rituximab.

Conclusion
Subcutaneous oedema in JDM is attributed to a vasculopathy. This is associated with severe rapidly progresssive disease with high mortality and requires aggressive immunosuppression. As seen in our patient disease is resistant to conventional treatment. Early recognition leads to better outcomes in these patients.

Disclosure
S. Janagan: None. W.A.E. Udeshika: None. P.M. Samarasinghe: None. J.D. Jagoda: None.
P098 Estimating the prevalence and predictors of musculoskeletal disability in Tanzania: a pilot study
Authors: Yongolo Nateiya M , Bunn Christopher , Halliday Jo , Mtesha Benson , Kelly Clive , Mwingwa Anthon , Biswaro Sanjura , Siebert Stefan , Hemed Asia , Walker Richard , McIntosh Emma , Mmbaga Blandina 
Published: April 2022

Abstract

Background/Aims
Musculoskeletal (MSK) disorders are among the major causes of disability worldwide, accounting for 20% of all years lived with disability. MSK disorders are linked to other non-communicable diseases (NCDs) as their adverse impact on mobility may promote the development of other NCDs. Prevalence studies of MSK disorders in Africa are limited with most coming from South Africa, while none have been previously performed in Tanzania. Screening for MSK disorders is not routinely conducted in health care facilities and there are no registered consultants working in this field in Tanzania. This pilot study aimed to provide an initial estimate of the prevalence and predictors of MSK disability to inform the design of a more detailed study of MSK disorders in Tanzania.

Methods
A cross-sectional pilot study was conducted in Kirima village, Hai District, Kilimanjaro region which has a total population of 1,911 people. We obtained ethical approval to invite each eligible individual to consent to supervised examination using the Gait, Arms, Legs and Spine (GALS) assessment tool (adults aged 18 years and over) or the paediatric GALS (pGALS) assessment tool (children aged 5 to 17 years old). In those where these screening tools detected an abnormality, we then performed a full Regional Examination of Musculoskeletal System (REMS). We also assessed functional status and physical disability in all GALS positive subjects using the Modified Health Assessment Questionnaire (MHAQ) tool. All adults were assessed during planned accompanied household visits, while a substantial number of the children were assessed while at school. Multivariable logistic regression analyses were carried out to assess the influence of demographic variables on GALS, REMS and MHAQ outcomes.

Results
A substantial number of adults (270) and children (491) could not be contacted or declined to consent to examination. Among the 1150 people who did consent, the prevalence of GALS/pGALS positivity was 8.2% (95% CI: 6.6-9.8), while REMS was positive in 3.5% (95% CI: 2.4-4.5). Female gender and increasing age were both significantly associated with each of GALS and REMS positivity. The MHAQ score was strongly associated with REMS positivity and significantly associated with GALS positivity, equating to worse function and greater disability.

Conclusion
These initial prevalence estimates and predictors of MSK disability are comparable to those seen elsewhere in the world. Greater detail on the prevalence of specific MSK disorders in Tanzania will require larger and more detailed studies.

Disclosure
N.M. Yongolo: None. C. Bunn: None. J. Halliday: None. B. Mtesha: None. C. Kelly: None. A. Mwingwa: None. S. Biswaro: None. S. Siebert: None. A. Hemed: None. R. Walker: None. E. McIntosh: None. B. Mmbaga: None.
P110 Adherence with mycophenolate mofetil in connective tissue disorders
Authors: Chauhan Aarti , Bunting Helen , Dubey Shirish 
Published: April 2022

Abstract

Background/Aims
Connective tissue disorders like systemic lupus erythematosus (SLE) are multi-organ systemic conditions characterised by disordered immune function. Mycophenolate mofetil (MMF) is commonly used for treatment of SLE and other connective tissue disorders. Compliance with drugs remains a significant issue in management of these conditions and varying reports from across the world continue to show significant lack of concordance resulting in increased disease activity and damage. The aim of this study was to investigate the adherence specifically with MMF treatment among patients attending clinics at University Hospitals Coventry and Warwickshire NHS Trust (UHCW)with SLE and other connective tissue disorders.

Methods
Ethical approval was obtained through research and development department within the Trust. This is a retrospective study collating non-identifiable hospital pharmacy data in patients who requested the prescription for MMF drug between January 2015 and December 2018. Clinical data were obtained from paper and electronic notes. Data were analysed using Microsoft Excel.

Results
We recruited 144 patients into this study with a wide age range from 18 to 91 years. Demographic data showed 100 out of 144 cases were females and 44 were males. There were 112 Caucasian patients, 22 of South Asian origin, 3 East Asian and 4 black patients. Of the 144 patients, SLE was the diagnosis for 56 patients and 88 patients had other diagnoses including scleroderma (18), mixed connective tissue disease (15), myositis (13), vasculitis (13) and Sjogren’s syndrome (10). Overall adherence with MMF was 68.3%. We found good adherence was seen in age group 41-60 years, tailing off in younger and older adults. The adherence rates were below 80% for all the age groups. Poor adherence with MMF correlated with 50% increase in risk of flares, with good adherence reducing the risk by 50% compared with overall risk of flares. We found a significant correlation between lack of compliance and risk of flares (r = 0.25, p &lt; 0.002). We compared the results for 112 Caucasian patients and 25 Asian patients which included South Asian and South East Asian patients. This showed a significant difference with reduced adherence among Asian patients (mean adherence 48%) in comparison to Caucasian patients (mean adherence 65%, p = 0.0055). There were no differences between SLE and other CTDs. We also did not find any trends with organ involvement, specifically with neurological involvement.

Conclusion
Adherence with MMF has improved considerably compared to previous studies. However, challenges remain and certain population groups such as young adults, elderly and Asian patients continue to have low adherence levels. Alternative strategies are needed to improve their health and reduce risk of flares and organ damage.

Disclosure
A. Chauhan: None. H. Bunting: None. S. Dubey: Honoraria; Lilly, Abbvie. Member of speakers’ bureau; Janssen.
P176 Meeting the demands of employment: the impact and rehabilitation of chronic pain and fatigue in the UK armed forces
Authors: Chisala Elijah , Bahadur Sardar 
Published: April 2022

Abstract

Background/Aims
The growing prevalence of chronic pain and the recent influx of post-viral fatigue (due to COVID-19) will limit the working output of the UK population. As such presentations become more common, the ability of the working population to meet the demands of their employment will depend on the effective management of chronic pain and fatigue.
We investigated the working ability and outcomes of UK military personnel two years after rehabilitation for persistent pain or fatigue.

Methods
We collected the health data of 35 personnel presenting with primary persistent pain, fibromyalgia, or persistent fatigue during admission to the 2-week Specialist Rehabilitation Course at DMRC between November 2018 to December 2019. Participants scored their current ability to work and the work-related impact of their symptoms by completing a follow-up survey. This group also evaluated the efficacy of 14 evidence-based rehabilitation tools provided during their rehabilitation programme based on how they improved their ability to work.

Results
88.2% of attendees had a history of mental health issues, whilst 82.4% had other medical comorbidities. Royal Air Force (RAF) personnel predominantly presented with fatigue rather than pain; this subgroup left the armed forces two years earlier than the service average. 62.9% of attendees responded to our survey. 63.6% of respondents no longer served in the military two years after their initial admission to the rehabilitation course. All current military personnel reported either “good” or “very good” symptom management and as a cohort reported better work outcomes than those who had left the military. Respondents reported mindfulness, activity pacing and education about symptoms as the most effective strategies for improving work capability. Those who found these strategies most useful had the best outcomes. 7 of the 8 retained military personnel found at least two of these strategies useful for improving their work ability compared to 4 of the 14 military leavers.

Conclusion
Poor working ability due to persistent pain or fatigue was not compatible with sustained military employment. Yet, the tools provided at DMRC improved the ability to work for those remaining in the military. Military personnel with persistent pain and fatigue benefitted most from mindfulness, activity pacing and education. Response to these specific strategies corresponded with both continued military service and better work capabilities. These findings are consistent with the recent literature regarding the efficacy of these rehabilitation strategies for persistent pain and fatigue. The occupational outcomes of military personnel in this study may be comparable to that of civilian populations; specifically sectors with similar demands or mental health risks as the armed forces.

Disclosure
E. Chisala: None. S. Bahadur: None.