Arthritis Care Research Articles

Canadian Veteran chronic disease prevalence and health services use in the five years following release: a matched retrospective cohort study using routinely collected data

BackgroundOccupational exposures may result in Canadian military Veterans having poorer health and higher use of health services after transitioning to civilian life compared to the general population. However, few studies have documented the physical health and health services use of Veterans in Canada, and thus there is limited evidence to inform public health policy and resource allocation.MethodsIn a retrospective, matched cohort of Veterans and the Ontario general population between 1990–2019, we used routinely collected provincial administrative health data to examine chronic disease prevalence and health service use. Veterans were defined as former members of the Canadian Armed Forces or RCMP. Crude and adjusted effect estimates, and 95% confidence limits were calculated using logistic regression (asthma, COPD, diabetes, myocardial infarction, rheumatoid arthritis, family physician, specialist, emergency department, and home care visits, as well as hospitalizations). Modified Poisson was used to estimate relative differences in the prevalence of hypertension. Poisson regression compares rates of health services use between the two groups.ResultsThe study included 30,576 Veterans and 122,293 matched civilians. In the first five years after transition to civilian life, Veterans were less likely than the general population to experience asthma (RR 0.50, 95% CI 0.48–0.53), COPD (RR 0.32, 95% CI 0.29–0.36), hypertension (RR 0.74, 95% CI 0.71–0.76), diabetes (RR 0.71, 95% CI 0.67–0.76), myocardial infarction (RR 0.76, 95% CI 0.63–0.92), and rheumatoid arthritis (RR 0.74, 95% CI 0.60–0.92). Compared to the general population, Veterans had greater odds of visiting a primary care physician (OR 1.76, 95% CI 1.70–1.83) or specialist physician (OR 1.39, 95% CI 1.35–1.42) at least once in the five-year period and lower odds of visiting the emergency department (OR 0.95, 95% CI 0.92–0.97). Risks of hospitalization and of receiving home care services were similar in both groups.ConclusionsDespite a lower burden of comorbidities, Veterans had slightly higher physician visit rates. While these visits may reflect an underlying need for services, our findings suggest that Canadian Veterans have good access to primary and specialty health care. But in light of contradictory findings in other jurisdictions, the underlying reasons for our findings warrant further study.

Investigating sex differences in T regulatory cells from cisgender and transgender healthy individuals and patients with autoimmune inflammatory disease: a cross-sectional study

<h2>Abstract</h2><h3>Background</h3> Sexual dimorphisms, which vary depending on age group and pubertal status, have been described across both the innate and adaptive immune system. We explored the influence of sex hormones on immune phenotype in the context of adolescent health and autoimmunity. <h3>Methods</h3> In this cross-sectional study, healthy, post-pubertal cisgender individuals (aged 16–25 years); healthy, pre-pubertal cisgender individuals (aged 6–11 years); transgender individuals (aged 18–19 years) undergoing gender-affirming treatment (testosterone in individuals assigned female sex at birth and oestradiol in individuals assigned male sex at birth); and post-pubertal cisgender individuals (aged 14–25 years) with juvenile-onset systemic lupus erythematosus (SLE) age-matched to cisgender individuals without juvenile-onset SLE were eligible for inclusion. Frequencies of 28 immune-cell subsets (including different T cell, B cell, and monocyte subsets) from each participant were measured in peripheral blood mononuclear cells by flow cytometry and analysed by balanced random forest machine learning. RNA-sequencing was used to compare sex and gender differences in regulatory T (Treg) cell phenotype between participants with juvenile-onset SLE, age-matched cis-gender participants without the disease, and age matched transgender individuals on gender-affirming sex hormone treatment. Differentially expressed genes were analysed by cluster and pathway analysis. Suppression assays assessed the anti-inflammatory function of Treg cells in vitro. <h3>Findings</h3> Between Sept 5, 2012, and Nov 6, 2019, peripheral blood was collected from 39 individuals in the post-pubertal group (17 [44%] cisgender men, mean age 18·76 years [SD 2·66]; 22 [56%] cisgender women, mean age 18·59 years [2·81]), 14 children in the cisgender pre-pubertal group (seven [50%] cisgender boys, mean age 8·90 [1·66]; seven [50%] cisgender girls, mean age 8·40 [1·58]), ten people in the transgender group (five [50%] transgender men, mean age 18·20 years [0·47]; five [50%] transgender women, mean age 18·70 years [0·55]), and 35 people in the juvenile-onset SLE group (12 [34%] cisgender men, mean age 18·58 years [2·35]; 23 [66%] cisgender women, mean age 19·48 [3·08]). Statistically significantly elevated frequencies of Treg cells were one of the top immune-cell features differentiating young post-pubertal cisgender men from similarly aged cisgender women (p=0·0097). Treg cells from young cisgender men had a statistically significantly increased suppressive capacity in vitro compared with those from cisgender women and a distinct transcriptomic signature significantly enriched for genes in the PI3K–AKT signalling pathway. Gender-affirming sex hormones in transgender men and transgender women induced multiple statistically significant changes in the Treg-cell transcriptome, many of which enriched functional pathways that overlapped with those altered between cisgender men and cisgender women, highlighting a hormonal influence on Treg-cell function by gender. Finally, sex differences in Treg-cell frequency were absent and suppressive capacity was reversed in patients with juvenile-onset SLE, but sex differences in Treg-cell transcriptional signatures were significantly more pronounced in patients with juvenile-onset SLE compared with individuals without juvenile-onset SLE, suggesting that sex hormone signalling could be dysregulated in autoimmunity. <h3>Interpretation</h3> Sex-chromosomes and hormones might drive changes in Treg-cell frequency and function. Young post-pubertal men have a more anti-inflammatory Treg-cell profile, which could explain inflammatory disease susceptibilities, and inform sex-tailored therapeutic strategies. <h3>Funding</h3> Versus Arthritis, UK National Institute for Health Research University College London Hospital Biomedical Research Centre, Lupus UK, and The Rosetrees Trust.

Validation of the Musculoskeletal Health Questionnaire in a general population sample: a cross-sectional online survey in Hungary

BackgroundThe Versus Arthritis Musculoskeletal Health Questionnaire (MSK-HQ) measures symptom severity and health-related quality of life (HRQoL) of people with musculoskeletal (MSK) conditions. We aimed to test the psychometric properties of the MSK-HQ among the general adult population and identify the determinants of MSK-HQ states. In addition, we aimed to explore the relationship between MSK-HQ and standard well-being measurement tools.MethodsThe translation proccess of the MSK-HQ into Hungarian followed the standard methods provided by the developer. A cross-sectional online survey was performed in Hungary involving a population normative sample (N = 2004, women: 53.1%; mean age: 48.3, SD = 16.6 years). Socio-demographic characteristics and self-reported MSK disorders were recorded. Alongside the MSK-HQ, standard measures of HRQoL (EQ-5D-5L), physical functioning (HAQ-DI) and well-being (ICECAP-A/O, WHO-5, Happiness VAS) were applied. Clinical and convergent validity were assessed by subgroup comparisons (Mann–Whitney-U and Kruskal–Wallis tests) and Spearman’s rank correlations. Internal consistency was assessed by Cronbach’s alpha. Test–retest reliability (N = 50) was evaluated by intraclass correlation coefficient (ICC). Predictors of MSK-HQ were analysed by ordinary least square multiple regressions.ResultsThe mean MSK-HQ index score was 44.1 (SD = 9.9). MSK-HQ scores were significantly lower in subgroups with self-reported MSK disorders. Correlations were strong between MSK-HQ and EQ-5D-5L (0.788), EQ VAS (0.644) and HAQ-DI (-0.698) and moderate with the well-being measures (p < 0.05). Cronbach’s alpha was 0.924 and ICC was 0.936 (p < 0.05). Being a man, living in the capital, having higher income and education were positively associated with MSK-HQ scores.ConclusionsThis is the first study to prove the validity and reliability of the MSK-HQ among the general public. The impact of socio-demographic characteristics on MSK-HQ scores deserves consideration in clinical studies.

Research priorities to reduce the impact of musculoskeletal disorders: a priority setting exercise with the child health and nutrition research initiative method.

SummaryInvolving research users in setting priorities for research is essential to ensure the outcomes are patient-centred and maximise its value and impact. The Musculoskeletal Disorders Research Advisory Group Versus Arthritis led a research priority setting exercise across musculoskeletal disorders. The Child Health and Nutrition Research Initiative (CHNRI) method of setting research priorities with a range of stakeholders was used, involving four stages and two surveys, to: (1) gather research uncertainties, (2) consolidate these, (3) score uncertainties against importance and impact, and (4) analyse scoring for prioritisation. 213 people responded to the first survey and 285 people to the second, representing clinicians, researchers, and people with musculoskeletal disorders. Key priorities included developing and testing new treatments, better treatment targeting, early diagnosis, prevention, and better understanding and management of pain, with an emphasis on understanding underpinning mechanisms. We present a call to action to researchers and funders to target these priorities.

Osteoarthritis & stroke: a bidirectional mendelian randomization study

The epidemiological evidence on the link between osteoarthritis (OA) and stroke remains inconclusive. Herein, we adopted a two-sample bidirectional Mendelian randomization (MR) study to determine the causality relationship between OA and stroke. Summary-level data derived from the published genome-wide association studies (GWAS) were employed for analyses. The data for OA at any site (n=455,211), knee OA (n=403,124), and hip OA (n=393,873) were obtained from a meta-analysis of GWAS available in the UK Biobank and Arthritis Research UK Osteoarthritis Genetics resources. The MEGASTROKE consortium provided data for stroke (n=446,696), ischemic stroke (IS) (n=440,328) and its subtypes, and intracerebral hemorrhage (ICH) (n=3,026). The main MR analysis was conducted by the inverse variance weighted (IVW) method. MR-Egger regression, MR pleiotropy residual sum and outlier, weighted median, Cochran Q statistic, and leave-one-out analysis approach were leveraged as supplements. We detected that higher risk of hip OA was significantly associated with overall stroke [IVW odds ratio (OR): 1.12, 95% confidence interval (CI): 1.06-1.20, P= 0.0002], IS (OR: 1.13, 95%CI: 1.06-1.21, P= 0.0003), and small vessel IS (OR: 1.25, 95%CI: 1.10-1.42, P= 0.0006). However, we found no evidence that stroke and subtypes had casual effects on OA in the reverse MR analyses. The present study provides genetic support that hip OA is a potential risk factor for overall stroke, IS, and small vessel IS. Further studies are warranted to elucidate the underlying mechanisms of causal associations between site-specific OA and stroke subtypes.

Research priority setting for paediatric rheumatology in the UK.

The evidence base that underlies the management of children and young people with paediatric rheumatic diseases is deficient. In this field, there are many crucial unanswered questions. The UK Paediatric Rheumatology Clinical Studies Group, supported by UK National Institute for Health Research Clinical Research Network: children and Versus Arthritis, elicited ideas for research priorities from paediatric rheumatologists, trainees, allied health-care professionals, nurse specialists, patients, parents of patients, carers, and charities. These ideas were collected through online surveys and face-to-face meetings. A modified Delphi process was used, which included online research priority ranking surveys and a consensus workshop. A longlist of 55 disease-specific research priorities and 37 general research priorities were voted on in the first survey. A list of 11 top general research priorities was produced. The top ten disease-specific research priorities were discussed in depth at a Delphi workshop to determine their final ranking. This Health Policy paper will help to guide clinicians, academics, and funding bodies to prioritise research in paediatric rheumatic diseases, specifically in areas of unmet patient needs.

Development of an interdisciplinary early rheumatoid arthritis care pathway

BackgroundTo develop an interdisciplinary care pathway for early rheumatoid arthritis (RA) including referral triage, diagnosis, and management.MethodsOur process was a four-phase approach. In Phase 1, an anonymous survey was electronically distributed to division rheumatologists. This provided data to a small interprofessional working group of rheumatology team members who drafted an initial care pathway informed by evidence-based practice in Phase 2. In Phase 3, an education day was held with approximately 40 physicians (rheumatologists and rheumatology residents), members of our interprofessional team, and two clinic managers to review the proposed care elements through presentations and small group discussions. The care pathway was revised for content and implementation considerations based on feedback received. Implementation of the care pathway and development of strategies for evaluation is ongoing across multiple practice sites (Phase 4).ResultsOur care pathway promotes an approach to patient-centered early RA care using an interdisciplinary approach. Care pathway elements include triage processes, critical diagnostics, pre-treatment screening and vaccinations, and uptake of suggested RA pharmacologic treatment using shared decision-making strategies. Pathway implementation has been facilitated by nursing protocols and evaluation includes continuous monitoring of key indicators.ConclusionThe ‘Calgary Early RA Care Pathway’ emphasizes a patient-centered and interdisciplinary approach to early RA identification and treatment. Implementation and evaluation of this care pathway is ongoing to support, highest quality care for patients.

I don't know what type of arthritis I have: A population-based comparison of people with arthritis who knew their specific type and those who didn't.

ObjectiveTo understand differences between people with arthritis who do not know their type (DK) compared to those reporting osteoarthritis (OA) or inflammatory and autoimmune types of arthritis (IAA), including the receipt of appropriate health care, information, and services.MethodsAnalysis of the Survey on Living with Chronic Disease in Canada–Arthritis Component. Respondents aged ≥20 years with health professional-diagnosed arthritis (n = 4,385) were characterized as reporting DK, OA or IAA. Variables: arthritis characteristics (duration, number and site of joints affected), arthritis impact (current pain and fatigue, difficulty in sleeping and daily activities, impact on life), health (self-rated general and mental health, life stress), arthritis management strategies (seeing health professionals, medication use, assistive devices, receipt of arthritis information, self-management activities). Multinomial logistic and log-Poisson regressions were used, as appropriate, to compare the DK to the OA and IAA groups.ResultsIn this arthritis sample, 44.2% were in the DK group, 38.3% reported OA and 17.5% reported IAA. Those in the DK group were more likely to be younger, have low income, low education, and be of non-white cultural background compared to those with OA. There were no significant differences in arthritis impact, but the DK group was less likely to have received information on, or have used, arthritis management strategies.ConclusionsThe sociodemographic characteristics of the DK group suggest they likely have lower health literacy. They were less likely to have accessed health care and other support services, indicating this is an important group for health education, both for individuals with arthritis and health care providers.

0798 Detriggered - a case of tenosynovitis ameliorated by CPAP

Abstract Introduction The influence of sleep quality and pain is bidirectional (1). Sleep loss can induce hyperalgesia through upregulated inflammatory mediators such as IL-6 and TNF (2, 3). Obstructive sleep apnea (OSA) is characterized by obstructive respiratory events, hypoxemia, sleep fragmentation, and ultimately poor quality sleep. Here we present a case of how the treatment of OSA with continuous positive airway pressure (CPAP) mitigated hand inflammation and trigger finger symptoms. Report of Cases: A 60 year old male with prediabetes, hypertension, and BMI 30 presented to primary care with bilateral finger pain and stiffness. Hand orthopedics noted a tender left A1-pully 4th finger with 20 degree flexion contracture and a palpable right 3rd finger flexor tendon nodule causing definite triggering. He was diagnosed with trigger finger and initially treated with steroid injections and again 5 months later due to persistent symptoms. 10 months after the initial orthopedic visit, orthopedics planned for surgical intervention, but patient missed his surgery for unknown reasons. 7 months later, sleep medicine evaluated the patient for snoring and daytime fatigue. He underwent home sleep apnea testing which revealed a respiratory event index (REI) of 36.7 which necessitated CPAP therapy. Unfortunately, the patient was then lost to follow up in sleep medicine clinic. More than a year later, the patient showed to clinic and found to have 100% CPAP compliance with residual REI of 0.7. He enthusiastically noted improvement of daytime fatigue and trigger finger symptoms when using CPAP. When he would forget to use CPAP at night or during naps, he would wake up with returned finger pain and stiffness. Per patient, the symptoms would then resolve after re-initiation of CPAP. This consistent association of CPAP and finger symptom amelioration continued even 8 months later in most recent follow up. Conclusion To our knowledge, this is the first report of trigger finger symptoms improving with treatment of OSA. One hypothesis is that through improved sleep quality, there is a dampening of chondrocyte proliferation of the retinacular sheath and allowing unrestricted motion of the flexor tendon (4). More studies are needed to evaluate the musculoskeletal benefits of CPAP for OSA. Support (If Any) 1. Haack M. Scott Sutherlandj. Et al. Pain sensitivity and modulation in primary insomnia. Eur J Pain. 2012, 16: 522-533.2. Chhangani BS, Roehrs Ta et al. Pain sensitivity in sleepy pain-free normals. Sleep, 209, 32:1011-1017.3. Li, Joule Sarah Appleton. Association of Musculoskeletal Joint Pain with Obstructive Sleep Apena, Daytime Sleepiness, and Poor Sleep Quality in Men. Arthritis Care and Research Vol 69. No 5. May 2017.4. Makkouk Al Hasan et al. Trigger finger: etology, evaluation, and treatment. Curr Rev Musculoskeltal Med 2008. 1:92-96.

Decision Needs and Preferred Strategies for Shared Decision-Making in Rheumatoid Arthritis: Perspectives of Canadian Urban Indigenous Women.

ObjectiveDecision‐making for treatment of rheumatoid arthritis (RA) is complex, with multiple beneficial medication options available, but with the potential for treatment‐related adverse effects and significant economic considerations. Indigenous patients make treatment decisions informed by an interplay of clinical, family, and societal factors. Shared decision‐making may represent an approach to support treatment decisions in a culturally congruent manner. Our objective was to identify aspects of arthritis care that Indigenous participants found relevant for shared decision‐making and to explore preferences for shared decision‐making strategies.MethodsA purposive sampling from rheumatology clinics that provide services to Indigenous patients in a Canadian urban center was used to recruit participants for interviews. Seven participants were recruited to reach content saturation. Interview content was coded by 2 individuals, including an Indigenous patient with RA, and the data were analyzed via thematic analysis.ResultsParticipants were all women ages 37–61 years living with RA. Participants supported the idea that shared decision‐making would be beneficial, primarily to support decisions around treatment plans and medication changes. Shared decision‐making approaches would need to reflect Indigenous‐specific content areas, such as benefits and risks of therapy informed by data from Indigenous patient populations and inclusion of traditional modes of healing. All participants were interested in having a decision coach and preferred that decision aids be in both paper and electronic formats for accessibility.ConclusionThis study advances knowledge in the priority areas and specific content needed in the shared decision‐making process and the preferences of shared decision‐making strategies relevant and appropriate for urban Indigenous women living with RA in Canada.

Issue Information

Arthritis Care & ResearchVolume 74, Issue 5 Issue InformationFree Access Issue Information First published: 25 April 2022 https://doi.org/10.1002/acr.24669AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Volume74, Issue5May 2022 RelatedInformation

P100 Research priorities to reduce the impact of musculoskeletal disorders

Abstract Background/Aims Involving research users in setting priorities for research is essential to ensure research outcomes are patient-centred and to maximise research value and impact. In 2019, Versus Arthritis convened a Musculoskeletal Disorders (MSKD) Research Advisory Group (RAG) which included 25 members: people with musculoskeletal conditions, researchers and healthcare professionals. The RAG identified a need for a research prioritisation exercise for adult non-inflammatory MSKD. Methods The Child Health and Nutrition Research Initiative (CHNRI) method was selected. The MSKD RAG identified, through consensus, four research Domains: Mechanisms of Disease; Diagnosis and Impact; Living Well with MSK disorders and Successful Translation. Following ethical approval, an initial electronic survey was distributed to stakeholders (people with musculoskeletal conditions, researchers, healthcare professionals, industry, research funders, healthcare providers, government and charities) asking for important research uncertainties in the four domains. Uncertainties were organised into themes and refined into research questions using a series of MSKD RAG workshops. Research questions underwent lay review to optimise readability. A second e-survey was distributed to stakeholders as above, where participants were asked to score each research question for two criteria, importance and impact, on a 1-10 numeric rating scale. Median criterion scores for impact and importance were calculated for each question and summed to create a total score. Research questions were ranked according to total score. Results The first survey had 209 respondents, who described 1290 research uncertainties, which were refined into 68 research questions. 285 people responded to the second survey, of which 189 fully completed. 74(39.2%) were public/lay responders, 48(25.4%) researchers, 43(22.8%) clinicians, 24(12.6%) other/unrecorded. The research questions, total scores and rankings are summarised in Table 1. Total scores ranged from 12 to 18 (maximum possible score 20). Conclusion For the first time, we have summarised priorities for research across MSKD, from discovery science to applied clinical and health research, including translation. Key priorities include developing and testing new treatments, better targeting of treatments, early diagnosis, prevention and better understanding and management of pain, with an emphasis on understanding the underpinning mechanisms. We present a call to action to researchers and funders to target these priorities. Disclosure Z. Paskins: Grants/research support; NIHR, Versus Arthritis, Royal Osteoporosis Society. C.E. Farmer: None. R.K. Jones: None. A. Clark: None. L. Troeberg: Grants/research support; Versus Arthritis. H. Pandit: Consultancies; Depuy J&amp;J, Zimmer Biomet, Smith and Nephew, Medacta International, Meril Life, JRI Orthopaedics, Invibio and Kennedy’s Law. Grants/research support; NIHR, VA (Versus Arthritis) and UKIERI (UK India Education and Research Initiative). S.M. Richardson: None. J. Loughlin: None. C.A. Brown: Grants/research support; Versus Arthrtitis. E.J. Taylor: None. C.L. Le Maitre: None. R.K. Wilcox: Grants/research support; EPSRC, Versus Arthritis, NIHR, DePuy Synthes. F.L. Bishop: None. E. Salt: None. E.M. Clark: Grants/research support; Versus Arthritis, NIHR. Other; I am Associate Editor of Journal of Bone and Mineral Research Plus for which I receive a salary, I am part of the Lot 2 provider for analysis of the national Joint Registry of England and Wales, funded by HQIP. D.A. Andersson: None. M. McCarron: None. D.J. Mason: None. C.M. Wilkinson: None. T. Barlow: None. G.M. Peat: None. F.E. Watt: Consultancies; Pfizer.

P282 ANA seroconversion during prior anti-TNF therapy abolishes anti-CCP antibody positivity as a predictor of abatacept retention in rheumatoid arthritis

Abstract Background/Aims Few long-term drug survival analyses have been reported for patients with rheumatoid arthritis (RA) treated with abatacept. Here we report a machine learning approach to investigate drug-survival of abatacept over 5 years in RA patients. Methods We performed a retrospective observational study on a tertiary hospital dataset of RA patients who started abatacept between January 2008 and December 2020. Time to abatacept discontinuation over 5 years was estimated using Kaplan-Meier survival analyses. A multivariate cox-proportional hazard model to predict abatacept discontinuation was chosen by random survival forest and partial least regression. Results A total of 112 RA patients (81% female, mean age 58.1 [SD 13.5] years) received abatacept. Mean disease duration was 18.3 months (SD 13.6). More than half (65/112) were co-prescribed at least one conventional synthetic DMARD (csDMARD). Methotrexate was the most frequently concomitant csDMARD (n = 37), followed by hydroxychloroquine (n = 23), sulfasalazine (n = 15), and leflunomide (n = 7). 42 (37.5%) patients were treated with glucocorticoids (intermittent or continuous) with abatacept. Abatacept was mostly used as 4th (n = 29) and 3rd line (n = 24) bDMARD, but 19 patients received abatacept as their first line bDMARD. 75 (67%) patients were rheumatoid factor (RF) positive and 73 (65.2%) were anti-citrullinated protein antibody (ACPA) positive. Anti-nuclear antibody (ANA) was positive (≥1:80) in 25 patients (pre-biologics) and 18 seroconverted to previously exposed anti-TNF (ANA seroconversion group). Abatacept was discontinued in 54 patients (48.2%); 19 (35.2%) due to an adverse event and 35 (64.8%) due to loss of efficacy. Overall, the median time to discontinuation of abatacept was 3.8 years. Multivariate cox-proportional hazard model revealed that ACPA positivity was associated with reduced risk of abatacept discontinuation with HR of 0.56 (95% CI 0.32-0.95,p=0.03) compared to the ACPA-negative group. In contrast, the ANA seroconversion group demonstrated worse retention of abatacept with HR of 2.67 (95% CI 1.39-5.16, p = 0.0033) compared to ANA-negative patients. Kaplan-Meier analysis demonstrated that in the ANA seroconversion group, retention of abatacept was significantly inferior to pre-anti-TNF ANA positive patients (p = 0.0084) and ANA-negative patients (p = 0.0041). ACPA positivity was associated with better survival only in the non-ANA seroconverted group with HR of 0.54 (95% CI 0.29-0.92, p = 0.041), after adjusted by propensity score. Combining abatacept with any csDMARDs reduced the risk of abatacept discontinuation with HR of 0.57 (95% CI 0.33-0.98, p = 0.043) after adjusting by propensity score. No statistical difference was found between first-line, second-line, or any subsequent chronology of use of abatacept. Conclusion Our data suggest that previous ANA seroconversion occurring whilst on anti-TNF therapy reduces subsequent abatacept retention and cancels out the protective effect of anti-CCP positivity. The mechanism through which this occurs is unclear and further prospective and mechanistic studies are needed to validate these findings. Disclosure J. Kimpton: None. M. Shipa: Grants/research support; MS is funded by Versus Arthritis. S. Yeoh: Grants/research support; SY is funded by the Royal College of Physicians, Rosetrees Trust, NIHR University College London Hospitals Biomedical Research Centre, UCLH Charities, and Versus Arthritis. E. Hawkins: None. M. Ehrenstein: Grants/research support; ME is supported (in part) by the University College London Hospital Biomedical Research Centre.

P137 Supporting patients to get the best from their osteoporosis treatment; what works for whom, why and in what circumstance: a rapid realist review

Abstract Background/Aims For two decades, clinicians and academics have been writing about the problem of poor adherence in osteoporosis, while people with osteoporosis have identified a need for more follow up and information about medicines. We aimed to understand what works in supporting people with osteoporosis to get the best from their medicines, and specifically, to understand what mechanisms enable components of interventions to support osteoporosis medication optimisation and the underlying contextual conditions that enabled these mechanisms. Methods We conducted a Rapid Realist Review. The scope was informed by a workshop of the Effectiveness Working Group of the Royal Osteoporosis Society Osteoporosis and Bone Research Academy and the approach informed by background syntheses of qualitative literature and the Perceptions and Practicalities Approach as an underpinning conceptual framework. A primary search identified observational or interventional studies which aimed to improve medicines adherence or optimisation. Included studies were assessed for quality and data extracted relating to context, mechanism and outcomes. A supplementary second search was conducted to gain additional insight on included key papers and emerging mechanisms. Extracted data were interrogated by authors independently for patterns of context-mechanism-outcome configurations and further discussed in weekly team meetings. Recommendations for research and clinical practice were co-developed with clinical and lay stakeholders. Results 41 papers were included. We identified five contextual timepoints for the person with osteoporosis (identifying a problem; starting medicine; continuing medicine) and the practitioner and healthcare system (making a diagnosis and giving a treatment recommendation; reviewing medicine) and mechanisms relating to patient informed decision making, treatment burden, supporting routinisation and memory, supporting clinical decision making, targeting support, and approaches which were integrated and sustainable. Interventions which support patient informed decision making, improve patient knowledge and understanding, have potential to influence long-term commitment to treatment, although few studies explicitly addressed patients’ perceptions of illness and treatment as recommended in NICE guidelines. During treatment, targeting additional consultations to those most in need may be a cost and clinically effective approach to enable this. Supporting primary care clinician decision making and integration of primary and secondary care services also appears to be important, in improving rates of treatment initiation and adherence. Supporting patients’ ability to adhere (eg by lowering treatment burden and issuing reminders) may be helpful to address practical difficulties but there is little evidence to support the use of reminders alone. Conclusion For medicines optimisation for people with osteoporosis, we suggest a need for more patient-centred interventions to address patients’ perceptions of illness and treatment, and reduce treatment burden. Specialist services should consider the extent to which they integrate with, and support primary care clinical decision-making, in order to impact long-term clinical outcomes. Specific research recommendations have been co-developed, to address these knowledge gaps. Disclosure Z. Paskins: Grants/research support; NIHR, Versus Arthritis, Royal Osteoporosis Society. O. Babatunde: None. A. Sturrock: None. L. Toh: None. R. Horne: None. I. Maidment: None.

P066 COVID Voices: co-produced research to explore the shielding experiences of people with inflammatory musculoskeletal disease

Abstract Background/Aims Up to one-third of people living with inflammatory arthritis or auto-immune disease may have been classified as ‘clinically extremely vulnerable’ (CEV) to COVID-19 and required to ‘shield’. Communication regarding shielding notification and details of how to shield were unclear, causing confusion and uncertainty. Most research into the impact of shielding on people living with musculoskeletal disease has involved either quantitative or survey-based data, with little patient involvement. This project aims to capture patient “stories” to understand and explore the experiences of people with inflammatory musculoskeletal conditions who shielded, using co-produced, qualitative methodology. Methods The Centre for Epidemiology Versus Arthritis (CfE) is committed to involving patients and the public, convening a COVID-19 Patient and Public Involvement (PPI) group early in the pandemic. Two PPI group members developed the research idea and collaborated with a clinical academic to co-produce a successful grant application to the Versus Arthritis “New opportunities” fund. The research aims to capture experiences and opinions on the processes for determining and communicating who is identified as CEV, and the impact of shielding upon individuals’ lives. We will develop recommendations to improve the process for subsequent pandemics. People who shielded due to inflammatory arthritis / auto-immune disease are invited to discuss their experiences of shielding in semi-structured interviews (n = 30) or focus groups (n = 12). Up to 50 participants may submit creative materials (artwork, poetry, photographs or written word), to include those unable, or unwilling, to speak about their experiences. A framework approach to thematic analysis of data generated from interviews and focus groups will be employed. Creative materials will be used to illustrate these themes. In addition to the core team, an experienced Patient Advisory Group will contribute to the analysis. Full ethical approval was awarded by the University of Manchester Research Ethics Committee. The ‘core team’ (two patient/public contributors and a clinical academic) are committed to ‘co-production’: working together in equal partnership, driven by values such as transparency, sharing power and inclusivity, which we anticipate will improve the relevance and quality of this work. Results Recruitment to interview and focus groups was exceeded within 10 days. Half the creative materials participants were recruited within a month, and recruitment remains open. The team have given invited talks at several national and regional events, discussing the research and methodological approach, demonstrating the significant interest generated by this work. Conclusion Although most funders now mandate some form of PPI in grant applications, research ideas conceived and genuinely co-produced by patient partners are rare. The CfE’s commitment to PPI enabled conversations and collaboration, which built on existing relationships, and led to successful grant funding. We look forward to further highlighting and sharing both the model of our collaboration, and the qualitative research findings. Disclosure J. Fox: None. L. Laidlaw: None. W.G. Dixon: Consultancies; WGD has received consultancy fees from Abbvie and Google, unrelated to this work. C. Sanders: None. C.A. Sharp: None.

P243 Anti-rituximab antibodies demonstrate neutralising capacity, associate with lower circulating drug levels and early relapse in patients undergoing treatment for systemic lupus erythematosus

Abstract Background/Aims A major limitation of biologic therapy is formation of anti-drug antibodies (ADA). We previously demonstrated that ADA to rituximab are more prevalent in patients undergoing treatment for systemic lupus erythematosus (SLE) than rheumatoid arthritis and vasculitis, and predict subsequent infusion reactions. However, little is known regarding the long-term dynamics of ADA to rituximab. In this study we evaluated the longitudinal impact of ADA positivity in terms of drug kinetics, treatment response and neutralising capacity in SLE. Methods Patients with SLE undergoing treatment with rituximab were recruited to this study (n = 35). Serum samples were collected at the following intervals post-treatment; 1-3 months, 6 months, 12 months, 36 months (n = 114). Clinical and laboratory data was collected pre-treatment and at each time point. ADA were detected using an electrochemiluminescent immunoassay. Serum rituximab levels were measured via ELISA. A complement dependent cytotoxic assay was used to determine neutralising capability of ADA in a subgroup of positive samples (n = 38). Results ADA were found to be persistently positive over the 36-month follow-up period in 64.3% of patients. There was no significant difference in baseline disease activity (BILAG / SLEDAI-2K) between those who were subsequently ADA positive vs negative. ADA positive patients were younger at diagnosis compared with ADA negative (mean 22.50 ± 9.10 vs 37.29 ± 11.31 years, p = 0.002). Multivariate logistic regression found older age at diagnosis was associated with reduced incidence of persistent ADA with a 22% decrease in risk for each addition year after diagnosis (p = 0.03). ADA positive patients had a significantly lower C3 level at baseline (mean 0.61 ± 0.23 vs 0.87 ± 0.30, p = 0.026), which remained lower at each subsequent time point post-treatment up to 12 months. ADA titres peaked earlier and remained higher in those who had been treated with rituximab previously compared with those who were rituximab naive (median 132 AU/ml vs 7 AU/ml at 1-3 months). At 6 months post-treatment, patients with detectable ADA had a significantly lower circulating drug level than ADA negative (p = 0.0018). In terms of clinical response, ADA positive patients had an initial significant improvement in disease activity (SLEDAI-2K) by 3 months (p &amp;lt; 0.001). However, response was not maintained at 12 months. In comparison, ADA-negative patients showed a significant improvement in SLEDAI-2K at 6 months and this was maintained across the 36-month follow-up period. BILAG defined relapse within 12 months of treatment was only seen in ADA positive patients. Finally, all ADA positive samples were found to neutralise rituximab in vitro. Conclusion ADA to rituximab were common and persisted over the 36 month period of this study. ADA associated with earlier drug elimination, increased relapse rates and demonstrated neutralising capacity suggesting that ADA could be a significant limitation to sustained response to treatment. Disclosure C. Wincup: Grants/research support; Lupus UK, Versus Arthritis, British Society for Rheumatology. N. Dunn: None. C. Ruetsch-Chelli: None. A. Manouchehrinia: None. N. Kharlamova: None. M. Naja: None. B. Seitz-Polski: None. D. Isenberg: None. A. Fogdell-Hahn: None. C. Ciurtin: None. E. Jury: None.

P193 How did people with rheumatoid arthritis experience the COVID-19 pandemic? Interim qualitative results from the BIORA-PAIN study

Background/AimsOver the last 12 months (September 2020-21), we have been conducting a clinical trial with two biologic agents comparing pain outcomes in rheumatoid arthritis (RA) (n = 26). Within the trial, we investigated how participants with RA taking immunosuppressive medication felt about their care and responded to the COVID-19 pandemic. Such information is important to guide healthcare providers.MethodsSemi-structured interviews were conducted either face-to-face or virtually with participants who had recently been recruited to the Biologics for Rheumatoid Arthritis Pain (BIORA-PAIN) study and attended a South West London hospital. Participants had a DAS-28-CRP score of above 5.1 and were just starting on biological treatment. Seven interviews were conducted between April-September 2021, lasting between 23-60 minutes during which participants were asked how they managed their RA during the pandemic. All the responding participants were female, aged between 27-74 (mean 50.3 years), with a mixture of employment status and some living alone or with others. Interviews were recorded then transcribed verbatim and an interim thematic analysis was conducted.ResultsFour main themes were identified: the effect of lockdown; care of self; medical care; and support. Participants reported weight gain during lockdown due to being more sedentary and feeling less able to exercise, which increased stiffness. Despite reporting no official advice from doctors regarding shielding, most participants felt more vulnerable due to awareness of immunosuppression, but protective measures and vaccine uptake alleviated fears. Many sought advice from online resources, such as Versus Arthritis, and support groups which, as well as comfort, provided information enabling some participants to ask doctors specific questions about their care and medications. Most participants were wary of misinformation and chose to use trusted websites such as NHS and gov.uk or sources advised by doctors. There were varied reports of participants’ experiences of their care: most participants felt that their care was largely unaffected by the pandemic, with all participants feeling able to obtain current medication. However, some felt the COVID-19 restrictions slowed the progress of their care and felt unsupported whilst suffering worsening symptoms. Face-to-face appointments were preferred over telephone appointments, as participants felt doctors were unable to assess their pain and joints via phone call. Participants who lived alone suffered more mentally.ConclusionParticipants in this study were wary of coronavirus in relation to their disease and many chose to shield whilst reporting no shielding guidance. Many participants looked for reliable sources to research their care and treatment, which have been increased by feeling less able to contact clinicians during the pandemic. Participants felt that routine treatment was possible via telephone but changes in their condition required face-to-face appointments.Disclosure A. Blundell: None. G. Mein: None. S. Koushesh: None. A. Omoruyi: None. A. Harrison: None. P. Sedgwick: None. N. Sofat: None.

P135 Lower limb muscle strength and balance in older adults with distal radius fracture: a systematic review

Abstract Background/Aims Distal radius fractures (DRF) are common fall-related fragility fractures disproportionately affecting older females. After a DRF, there is an increased risk of future fragility fractures and functional decline. Systematic review evidence shows balance and muscle strengthening exercises reduce falls in older adults. Despite this, existing DRF rehabilitation trials have mainly focused on upper limb impairments. To inform rehabilitation requirements, we aimed to 1.) compare lower limb muscle strength and balance between older adults with a DRF with age- and sex-matched controls, and 2.) synthesise lower limb muscle strength and balance outcomes in older adults with a DRF. Methods We searched Embase, MEDLINE and CINAHL (1990 to August 2021). We included randomised and non-randomised controlled trials, and observational studies, that assessed lower limb strength and/or balance in adults aged ≥50 years enrolled within one year after a DRF. Strength and balance had to be assessed using validated instrumented or physical performance measures. Two reviewers independently screened titles and abstracts, and full-text reports of potentially eligible studies. One reviewer extracted data, then checked by another. Two reviewers independently appraised studies using the Cochrane risk-of-bias tool or Newcastle-Ottawa scale. We synthesised results narratively due to heterogeneity. PROSPERO registration: CRD42020196274. Results Seventeen studies (10 case-control studies, three RCTs and four case-series) including 1112 participants (95% women) with a DRF were included. Participants’ mean age ranged from 56 to 73 years; median sample size was 80 (IQR 54-106). Eleven (65%) studies assessed lower limb muscle strength using 10 different methods. Knee extensor strength assessment was most common (5/11 studies) followed by the 30-second and five times sit-to-stand tests (3/11 studies). All studies assessed balance, using 14 different methods. Single leg balance assessment was most common (6/17 studies) followed by functional reach and postural sway (3/17 studies). 5/10 case-control studies assessed lower limb muscle strength. Two studies found cases performed worse than controls during sit-to-stand tests; three studies assessed knee extensor strength with conflicting findings. All case-control studies assessed balance, with cases demonstrating impaired balance compared to controls on some measures. 4/17 studies assessed strength and 6/17 studies assessed balance at multiple timepoints. Over time, strength progressively improved in 3/4 studies but changes in balance were inconsistent across studies. Conclusion There is some evidence that older adults with a DRF have impaired lower limb muscle strength and balance compared to age- and sex-matched controls, but findings are inconsistent. Synthesis of results was limited by heterogeneity in the design, quality, and assessment methods used in included studies. Large-scale robust case-control and/or prospective observational studies are needed to better establish the rehabilitation requirements for this population. Disclosure C. Forde: Grants/research support; CF is supported by the NIHR Biomedical Research Centre, based at Oxford University Hospitals Trust, Oxford. P.J.A. Nicolson: Grants/research support; PN is supported by a Versus Arthritis Foundation Fellowship (ref. 22428). C. Vye: None. J.C.H. Pun: Grants/research support; JP received financial support from the NMAHPs Internship Versus Arthritis (Grant reference 22082). W. Sheehan: None. M. Costa: Grants/research support; MC receives grants from NIHR and related health charities. S.E. Lamb: Grants/research support; SL receives grants from NIHR and related health charities. D.J. Keene: Grants/research support; DK is supported by a National Institute of Health Research (NIHR) Postdoctoral Fellowship (ref. PDF-2016-09-056) and by the NIHR Biomedical Research Centre, based at Oxford University Hospitals Trust.

P054 Vascular Ehlers-Danlos syndrome: a life-altering diagnosis not to be missed

Abstract Background/Aims A 41-year-old lady underwent a laparotomy and small bowel resection for small bowel obstruction due to adhesions after presenting with a three-day history of abdominal pain. The surgery was complicated by significant bleeding from multiple points of the mesentery and a laceration of the uterine fundus, the repair of which was complicated due to extremely friable tissue. Post-operative ileus, fever, tachycardia, and raised inflammatory markers led to antibiotic therapy and further investigation with computed tomograph angiography (CTA) abdomen which identified a retroperitoneal haematoma due to a herald bleed from an adrenal artery pseudoaneurysm and multiple further true aneurysms in the coeliac, splenic, and right posterior hepatic arteries. The right adrenal artery aneurysm was treated by right renal artery stent graft as targeted embolisation was not possible due to extremely friable arterial intima that dissected and bled on instrumentation. The rheumatology team was consulted to advise on the possibility of vasculitis and whether treatment with immunosuppressives was indicated. Methods Prior to this admission, she denied any fever, weight loss, rash or neuropathies. There was a history of spontaneous peri-renal haematoma and easy bruising. She had three successful pregnancies; two were Caesarean section deliveries, one of which was complicated by post-partum bleeding. There was no family history of connective tissue diseases, sudden deaths, aneurysms or visceral ruptures. There were no clinical features of connective tissue disease. She was noted to have acrogeria, small finger joint hypermobility, large eyes, a small nose, and absent earlobes. There were prominent veins on her lower back, chest, arms, and legs. She had a normal palate arch, normal appearances of previous surgical scars, and there was no skin hyperextensibility. Results Inflammatory markers prior to admission were normal, with no cytopenias or thrombocytosis. ANA, ENA, ANCA, HIV, Hepatitis B/C, treponemal antibody, and rheumatoid factor/anti-CCP were negative. CTA showed no thickening suggestive of vascular/perivascular inflammation. Histopathology of resected small bowel and mesentery showed no evidence of vasculitis. A diagnosis of probable vascular Ehlers-Danlos syndrome (EDS) was made. She was not treated with steroids. Genetic testing confirmed a heterozygous mutation for a pathogenic missense variant in the COL3A1 gene: c.574G&amp;gt;C,p.(Gly192Arg), not previously reported to be associated with disease. Her inflammatory markers improved over time. She was discharged on celiprolol for blood pressure control and close surveillance of aneurysms. An extended screen for the presence of aneurysms elsewhere showed a left vertebral artery aneurysm and dissection at the C4/5 intervertebral foramen on CTA head. Genetic testing was offered to her family members, especially her three sons. Conclusion Vascular EDS is under-recognised and should be in the differential diagnosis of non-inflammatory vasculitis mimics in patients presenting with arterial ruptures, dissections or aneurysms to avoid potentially harmful treatment with immunosuppressive therapy. Disclosure S. Yeoh: Grants/research support; Versus Arthritis (unrelated to this work). C. von Stempel: None. C. Thornton: None. S. Yalamanchili: None. J. Manson: None.

P246 Revision to musculoskeletal domain of BILAG-2004 index to incorporate ultrasound findings

Abstract Background/Aims The BILAG-2004 index grades musculoskeletal (MSK) inflammation as mild (C), moderate (B) and severe (A), based on clinical features. In a recent study, 27% of SLE patients with MSK pain have ultrasound (US) synovitis without swelling, and respond better to therapy than those with normal ultrasound. We aimed to revise the MSK domain of the BILAG-2004 index to improve its utility in modern practice. Methods An MSK sub-committee reviewed the existing BILAG-2004 MSK definitions and glossary, then re-analysed data from recent studies to propose revised definitions. Results The new definitions/changes are: (i) BILAG-C arthralgia (if US is not performed) is defined as a classical inflammatory symmetrical small-joint distribution of symptomatic joints on clinical assessment, based on the features most associated with US inflammation in a previous study. If US is performed, all previous BILAG-C patients are reclassified: (ii) BILAG-B now includes patients without swelling if they have significant synovitis/tenosynovitis on US in symptomatic joints/tendons; (iii) patients with arthralgia without swelling are scored as BILAG-D instead of C, if US of the symptomatic joints has been performed and is normal; (iv) a more detailed definition of functional impairment is provided for BILAG-A. Data from 221 symptomatic SLE patients (BILAG-A-C) in two recent studies were re-analysed in the light of the above changes. 121/221 (54.8%) were graded clinically as having arthralgia / myalgia (BILAG-C) on BILAG-2004 . Of these, 53/121 (43.8%) had evidence of synovitis (GS &amp;gt; 1 or PD &amp;gt; 0) or tenosynovitis (GS &amp;gt; 0 or PD &amp;gt; 0) on US. The effect on grading if US were performed on all BILAG C cases is shown in table 1. Conclusion Future versions of the BILAG index will allow the use of US to classify patients who are graded as mild inflammatory arthritis (BILAG-C) to moderate (BILAG-B) or non-inflammatory pain (BILAG-D/E). Although US is not required for all assessments it may be used when there is diagnostic uncertainty. This is in keeping with clinical practice in inflammatory arthritis care, and similar to use of other investigations (e.g. renal biopsy) that contribute to BILAG assessments of other systems. Disclosure R.D. Sandler: None. E.M. Vital: None. A. Prabu: None. C. Riddell: None. K.I. Mahmoud: None. L. Teh: None. C.J. Edwards: None. C. Yee: None.