Early intervention has been the cornerstone of improving outcomes in patients with rheumatoid arthritis. Over the past decade, the boundaries have been pushed in an attempt to achieve effective prevention strategies in those who are at high risk of developing rheumatoid arthritis. Core risk factors including the presence of serum anti-citrullinated protein antibodies, arthralgia and subclinical inflammation on imaging are highly predictive of arthritis development. The influence of air pollution, diet and the role of microbiome on disease progression are less clear. In turn, therapeutic focus has shifted to an earlier pre-arthritis phase of the disease continuum where the clinically apparent arthritis may potentially be intercepted. Seven proof-of-concept interventional trials in at-risk individuals have been conducted so far. Whether true prevention of rheumatoid arthritis is possible remains elusive. Promising signals towards permanent disease modulation and improvement in symptom burden were seen with some immunomodulatory therapies, whilst others were unsuccessful. Long-term follow-up is required to ascertain a true effect. Looking forward, a better understanding of the natural history and underlying biological mechanisms of arthritis development and more accurate, validated risk stratification is needed.

OBJECTIVES:To compare the magnitude of cognitive impairment against age-expected levels across the immune mediated inflammatory diseases (IMIDs: systemic lupus erythematosus [SLE], rheumatoid arthritis [RA], axial spondyloarthritis [axSpA], psoriatic arthritis [PsA], psoriasis [PsO]).METHODS:A pre-defined search strategy was implemented in Medline, Embase and Psychinfo on 29/05/2021. Inclusion criteria were: (i) observational studies of an IMID, (ii) healthy control comparison, (iii) measuring cognitive ability (overall, memory, complex attention/executive function, language/verbal fluency), and (iv) sufficient data for meta-analysis. Standardised mean differences (SMD) in cognitive assessments between IMIDs and controls were pooled using random-effects meta-analysis. IMIDs were compared using meta-regression.RESULTS:In total, 65 IMID groups were included (SLE: 39, RA: 19, axSpA: 1, PsA: 2 PsO: 4), comprising 3141 people with IMIDs and 9333 controls. People with IMIDs had impairments in overall cognition (SMD: -0.57 [95% CI -0.70, -0.43]), complex attention/executive function (SMD -0.57 [95% CI -0.69, -0.44]), memory (SMD -0.55 [95% CI -0.68, -0.43]) and language/verbal fluency (SMD -0.51 [95% CI -0.68, -0.34]). People with RA and people with SLE had similar magnitudes of cognitive impairment in relation to age-expected levels. People with neuropsychiatric SLE had larger impairment in overall cognition compared with RA.CONCLUSIONS:People with IMIDs have moderate impairments across a range of cognitive domains. People with RA and SLE have similar magnitudes of impairment against their respective age-expected levels, calling for greater recognition of cognitive impairment in both conditions. To further understand cognition in the IMIDs, more large-scale, longitudinal studies are needed.

The last British Society for Rheumatology (BSR) guideline on PMR was published in 2009. The guideline needs to be updated to provide a summary of the current evidence for pharmacological and non-pharmacological management of adults with PMR. This guideline is aimed at healthcare professionals in the UK who directly care for people with PMR, including general practitioners, rheumatologists, nurses, physiotherapists, occupational therapists, pharmacists, psychologists and other health professionals. It will also be relevant to people living with PMR and organisations that support them in the public and third sector, including charities and informal patient support groups. This guideline will be developed using the methods and processes outlined in the BSR Guidelines Protocol. Here we provide a brief summary of the scope of the guideline update in development.

Background Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are common inflammatory rheumatic diseases with distinct clinical phenotypes, that can both result in significant disability. Whilst some data in selected samples report no difference in Health Assessment Questionnaire scores (HAQ) between RA and PsA(1), there is a lack of definitive long term population based data. The Norfolk Arthritis Register (NOAR) is an inception cohort of early inflammatory arthritis established in 1989, with over 4,500 cases of new onset inflammatory arthritis. Cases were recruited in primary care or from hospital clinics, and inclusion criteria were age >16 years with 2 swollen joints lasting ≥4 weeks. Data was collated on demographics and disability through Health Assessment Questionnaires (HAQ) over variable years of follow up (0-20 years); HAQ scores values range from 0 to 3, and the higher the score the greater the disability [2]. Objectives Our aim was to compare differences between both baseline and follow-up HAQ scores in RA and PsA, in cases selected from the same base population and followed continuously for over 20 years. Methods Cases included in this study were recruits into NOAR, who were followed at intervals of 1, 2, 3, 4, 5, 7, 8, 10, 12, 15, 18 and 20 years. Cases of RA were defined using American College of Rheumatology (ACR) criteria; cases of PsA were classified by retrospective clinical record review. Cases with RA were compared to cases with PsA, and data analysis was carried out in R. Independent samples t-tests were used to assess statistical significance of unadjusted HAQ scores. Results A total of 1,812 cases of RA (85.4%) and 308 cases of PsA (14.5%) were identified with complete data on sex and age within the NOAR cohort who had recorded HAQ scores. The mean age of onset for RA was 56.3 years (min 18.6 – max 88.6; SD 13.9), and 47.3 years for PsA (min 16 – max 79.9, SD 13.1). Baseline HAQ Mean baseline HAQ scores were higher for RA at 0.854 (SD 0.704) when compared with PsA at 0.706 (SD 0.688) (p<0.001). Females had higher baseline HAQ scores than males (0.915 vs 0.677) consistent across both disease types which was statistically significant (RA – 0.919 vs. 0.716, p <0.001: PsA – 0.885 vs. 0.533, p <0.001). Follow-up HAQ Cases were followed up to 20 years. 1,812 cases of RA were identified at baseline, decreasing to 1552 with 1-year follow up (85.6%) and 165 cases with 20-year follow up (9.1%). 308 PsA cases were identified at baseline, 248 followed up at 1-year (80.5%) and 21 cases for 20-years (6.8%). Figure 1 illustrates that cases with RA had higher mean HAQ scores than PsA throughout a follow up period of up to 20 years. Mean HAQ scores accumulated over the follow up period for RA, whilst there was a decrease in HAQ scores after 12 years of follow up for those with PsA before increasing after 18 years. Conclusion The NOAR cohort is unique in its long follow up period of up to 20 years, allowing for the assessment of HAQ longitudinally. The relationship between higher HAQ scores in RA than PsA holds for both baseline HAQ scores and follow-up HAQ scores throughout the follow-up period, supporting the association of RA with greater disability. We hypothesise that this may be due to the nature of joint damage and other comorbidities associated with RA. We also demonstrate from this data that females present with statistically higher baseline HAQ scores than males within both diseases. In conclusion, there are evident trends with higher HAQ scores in RA over PsA consistent over time. References [1]Sokoll KB, Helliwell PS. Comparison of disability and quality of life in rheumatoid and psoriatic arthritis. J Rheumatol. 2001 Aug;28(8):1842–6. [2]Uhlig T, Haavardsholm EA, Kvien TK. Comparison of the Health Assessment Questionnaire (HAQ) and the modified HAQ (MHAQ) in patients with rheumatoid arthritis. Rheumatology. 2006 Apr 1;45(4):454–8. Acknowledgements: NIL. Disclosure of Interests None Declared.

Background Age strongly influences cognitive ability. Previous studies have tried to compare the cognitive ability of people with different immune mediated inflammatory diseases (IMIDS: systemic lupus erythematosus [SLE], rheumatoid arthritis [RA], axial spondyloarthritis [axSpA], psoriatic arthritis [PsA], psoriasis [PsO]) in age-matched analyses. However, given the varying age of onset of these conditions, within direct age-matched comparisons one of the disease groups is necessarily older/younger than typical. Objectives (i) To perform a systematic review of the cognitive ability of people with IMIDs compared with age-matched controls, and (ii) use meta-regression to indirectly compare the cognitive ability of people with different IMIDs. Methods A search strategy was implemented in the Medline, Embase and PsychInfo databases on 29.5.2021. Identified studies were screened by two reviewers, selecting observational studies comparing the cognitive ability of people with an IMID against healthy controls. This abstract only includes studies reporting overall cognition scores, memory scores and attention scores. The standardised mean differences (SMDs) of the cognitive assessments between people with IMIDs and controls were pooled using random-effects meta-analysis, stratified by IMID. The IMIDs were compared using meta-regression, to identify the IMID with the greatest impairment in cognitive ability compared with healthy people of a similar age (inclusion cut-off: ≥5 studies). Results In total, 62 studies (SLE: 37, RA: 18, axSpA: 1, PsA: 2, PsO: 4) were included in the meta-analyses. People with IMIDs had moderate impairments in overall cognition, memory and attention compared with controls (Table 1), with similar results seen when limiting analyses to studies which included age-matched controls (N=48 studies). People with SLE and RA had similar levels of impairment compared with controls of comparable age in terms of overall cognition (coef: -0.12 (95% CI -0.42, 0.19) and attention (coef: -0.35 (95% CI -0.73, 0.04)). Other IMIDs and cognition dimensions were not included in the meta-regression analysis due to lack of studies. Table 1. Results of meta-analyses Standardised mean difference (95% Confidence Interval) [N studies] Systemic lupus erythematosus Rheumatoid arthritis Axial spondyloarthritis Psoriatic arthritis Psoriasis Overall cognition All -0.55 (-0.70. -0.39) [18] -0.59 (-0.82, -0.35) [13] -0.66 (-1.11, -0.21) [1] -0.50 (-0.78, -0.21) [2] -0.51 (-1.09, 0.07) [3] Age-matched -0.55 (-0.72, -0.38) [14] -0.66 (-0.92, -0.41) [11] -0.66 (-0.11, -0.21) [1] -0.61 (-1.08, -0.14) [1] -0.77 (-1.39, -0.16) [2] Attention All -0.51 (-0.63, -0.38) [27] -0.79 (-1.10, -0.47) [9] -0.58 (-1.03, -0.13) [1] - -0.14 (-0.42, 0.14) [2] Age-matched -0.51 (-0.67, -0.36) [21] -0.87 (-1.35, -0.39) [6] -0.58 (-1.03, -0.14) [1] - -0.36 (-0.75, 0.04) [1] Verbal memory (immediate ) All -0.59 (-0.79, -0.38) [19] -1.00 (-1.47, -0.53) [7] - - -0.52 (-1.05, 0.02) [3] Age-matched -0.61 (-0.90, -0.32) [12] -1.42 (-1.73, -1.12) [4] - - -0.72 (-1.42, -0.02) [2] Verbal memory (delayed ) All -0.44 (-0.57, -0.31) [18] -0.93 (-1.48, -0.38) [5] -0.23 (-0.67, 0.21) [1] - -0.52 (-1.52, 0.49) [2] Age-matched -0.39 (-0.56, -0.21) [12] -1.40 (-1.76, -1.03) [3] -0.23 (-0.67, 0.21) [1] - -1.05 (-1.47, -0.63) [1] Non-Verbal memory (immediate ) All -0.41 (-0.57, -0.25) [15] -0.32 (-1.23, 0.58) [1] -0.21 (-0.62, 0.23) [1] - - Age-matched -0.34 (-0.52, -0.16) [10] - -0.21 (-0.62, 0.23) [1] - - Non-Verbal memory (delayed ) All -0.45 (-0.63, -0.27) [16] -0.41 (-0.91, 0.08) [1] -0.14 (-0.58, 0.30) [1] - - Age-matched -0.46 (-0.75, -0.17) [10] -0.41 (-0.91, 0.08) [1] -0.14 (-0.58, 0.30) [1] - - Conclusion People with IMIDs have significant impairments in terms of overall cognition, memory and attention. Whilst this indirect analysis shows that people with SLE and RA have a similar magnitude of impairment compared with healthy controls of a similar age, a number of factors could be influencing this finding (e.g. selection bias, demographic differences). Disclosure of Interests None declared

Plasma exchange (PLEX) is often recommended as an adjunctive therapy for patients with ANCA-associated vasculitis (AAV) in the setting of rapidly progressive glomerulonephritis or diffuse alveolar haemorrhage. Since ANCAs are pathogenic, it seems a reasonable and justified approach to remove them through therapeutic PLEX, as despite advances in immunosuppressive therapy regimens, AAV is associated with significant morbidity and death. However, the association between ANCA levels and mortality or disease activity is uncertain. In addition, any treatment must be judged on the potential risks and benefits of its use. Here, we summarise the current data on PLEX usage in patients with AAV. The largest randomised trial to date the Plasma Exchange and Glucocorticoids in Severe ANCA-Associated Vasculitis (PEXIVAS) study failed to show added benefit for PLEX on the prevention of death or end-stage renal failure (ESRF) for the management of patients with severe AAV. However, there is a possibility that PLEX delays dialysis dependence and ESRF in the early stages of the disease. Regardless of whether this is only for 3 to 12 months, this could be of clinical significance and a substantial improvement in patient’s quality of life. Cost utility analysis and trials including patient-centred outcomes are required to evaluate the use of PLEX. Furthermore, ascertaining those at high risk of developing ESRF could help identify those who may benefit from PLEX the most, and further insights are required in setting of diffuse alveolar haemorrhage.

Objective. The aim was to compare the cognitive ability of people with RA with healthy controls (HCs). Methods. People with RA were recruited from the Norfolk Arthritis Register (NOAR), a population-based cohort study of people with inflammatory arthritis. Data on aged-matched HCs (people with no cognitive impairment) came from the comparison arm of The Dementia Research and Care Clinic Study (TRACC). People with RA and HCs performed a range of cognitive ability tasks to assess attention, memory, verbal fluency, language, visuospatial skills, emotional recognition, executive function and theory of mind. A score of <88 on the Addenbrooke's Cognitive Examination III was considered cognitive impairment. Scores were compared using linear regression adjusting for age, sex, smoking status, education, BMI, anxiety and depression. Results. Thirty-eight people with RA [mean (S.D.) age: 69.1 (8.0) years; 25 (65.8%) women] were matched with 28 HCs [mean (S.D.) age: 68.2 (6.4) years; 15 (53.6%) women]. Twenty-three (60.5%) people with RA were considered to have mild cognitive impairment [mean (S.D.) Addenbrooke's Cognitive Examination III: RA = 85.2 (7.4), HC = 96.0 (2.5)]. People with RA had impairments in memory, verbal fluency, visuospatial functioning, executive function and emotional recognition in faces compared with HCs, after adjustment for confounders. Conclusion. People with RA had cognitive impairments in a range of domains. People with RA might benefit from cognitive impairment screening to allow for early administration of appropriate interventions.

Background:The risk of cognitive decline and dementia is of particular interest for patients exposed to prolonged inflammation. In rheumatoid arthritis (RA), the inflammatory mechanisms that are central to the disease’s pathology share many features with those seen in Alzheimer’s disease (AD). However, published reports on the strength and direction of the putative associations with cognitive decline and dementia in RA are conflicting and the potential impact of immunomodulation has not been fully established. This study reports on a case control analysis comparing the results of a cognitive test conducted in RA cases from a longitudinal population register with healthy controls. The relationship between test outcomes, disease characteristics, and treatment is examined.Objectives:To characterise differences in cognitive function as assessed by a validated test battery between a group of patients with RA and a matched sample of healthy controls.To investigate disease and treatment related factors that might have an impact on the cognitive function of patients with RA.Methods:A total of 38 people with RA were selected at random from subjects who had enrolled on the Norfolk Arthritis Register as part of the ICORA (Investigation of Cognition in RA) Study. The register is a large longitudinal inception cohort of patients recruited from both primary and secondary care. The study subjects were over 55 years old with a diagnosis of RA defined by the ACR criteria. Cognitive function was assessed using the Addenbrooke’s Cognitive Examination III (ACE-III) battery. The ACE-III is a validated screening test for dementia that evaluates five cognitive domains (attention, memory, verbal fluency, language and visuospatial skills). A cut off value of 82 is indicative of cognitive impairment. The ACE-III scores in the cases were compared with scores from 29 healthy population-based controls matched for age and sex.Results:The mean age of the patient and control groups was 69 years. The RA patients had a mean disease duration of 9.8 years and had been taking DMARDs for 7.1 years. Among the patient group with RA, 14 (37%) scored below 82 compared with none in the group of healthy controls. The mean ACE-III scores of both groups are shown in the table below:Controls N=29RA N=38ACE-III Total95.2 (3.7)85.2 (7.4)•Attention17.7 (0.5)16.5 (1.9)•Memory24.6 (1.9)19.8 (4.0)•Fluency12 (1.4)9.9 (2.6)•Language25.5 (0.8)24.6 (1.7)•Visuospatial15.8 (0.5)14.4 (1.5)After adjusting for age, sex, BMI and smoking status, significant differences were seen in the ACE-III total (adjusted mean difference(SE)=8.67(1.77); p<0.001), memory (adjusted mean difference(SE)=4.16(1.03); p<0.001), fluency (adjusted mean difference(SE)=2.29(0.67); p=0.001) and visuospatial (adjusted mean difference(SE)=1.36(0.38); p<0.001). There was no difference in attention (p=0.19) or language (p=0.10).Among the patients with RA there was no clear association between disease duration and ACE-III Total scores; however, there was a trend for increasing cognitive scores in those who had been taking DMARDs for longer (<5 years: mean ACE-III Total=84.1; 5-10 years: 85.0: 11-14 years: 85.4; >14 years: 89.6).Conclusion:This study provides evidence to suggest that patients with established RA are at increased risk of cognitive decline when compared with healthy controls. The pattern of cognitive deficit, predominantly involving visuospatial and memory function, is consistent with an Alzheimer’s disease profile. Our data suggest a potential role for DMARDs in reducing the rate of cognitive decline in patients with RA.Disclosure of Interests:Tasuku Toyoda: None declared, Jacqueline Chipping: None declared, Jack Dainty: None declared, Stephen Jeffs: None declared, Michael Hornberger: None declared, Eneida Mioshi: None declared, Suzanne Verstappen Grant/research support from: BMS, Consultant of: Celltrion, Speakers bureau: Pfizer, Max Yates: None declared, Alex MacGregor: None declared