OBJECTIVES:To assess whether prodromal symptoms of RA, as recorded in the Clinical Practice Research Datalink Aurum (CPRD) database of English primary care records, differ by ethnicity and socioeconomic status. METHODS:A cross-sectional study to determine the coding of common symptoms (≥0.1% in the sample) in the 24 months preceding RA diagnosis in CPRD Aurum, recorded between 1 January 2004 and 1 May 2022. Eligible cases were adults with a code for RA diagnosis. For each symptom, a logistic regression was performed with the symptom as dependent variable, and ethnicity and socioeconomic status as independent variables. Results were adjusted for sex, age, BMI and smoking status. White ethnicity and the highest socioeconomic quintile were comparators. RESULTS:In total, 70 115 cases were eligible for inclusion, of which 66.4% were female. Twenty-one symptoms were coded in >0.1% of cases so were included in the analysis. Patients of South Asian ethnicity had higher frequency of codes for several symptoms, with the largest difference by odds ratio being muscle cramps (1.71, 99.76 % confidence interval 1.44-2.57) and shoulder pain (1.44, 1.25-1.66). Patients of Black ethnicity had higher prevalence of several codes including unintended weight loss (2.02, 1.25-3.28) and ankle pain (1.51, 1.02-2.23). Low socioeconomic status was associated with morning stiffness (1.74, 1.08-2.80) and falls (1.37, 2.03-1.82). CONCLUSION:There are significant differences in coded symptoms between demographic groups, which must be considered in clinical practice in diverse populations and to avoid algorithmic bias in prediction tools derived from routinely collected healthcare data.

Objective The field of rheumatoid arthritis (RA) is moving towards identification of and intervention in people at risk of RA, but a validated risk stratification method is lacking. This work was undertaken to develop a risk stratification method for persons presenting with arthralgia considered to be at risk of RA. Methods A joint EULAR/American College of Rheumatology (ACR) expert committee was established. Risk factor and outcome data from 10 arthralgia cohorts (including clinically suspect arthralgia and autoantibody-positive arthralgia) were studied. The work focused on differentiating the risk of progression to clinically apparent inflammatory arthritis (IA) within 1 year, using clinical and serologic variables, without and with subclinical joint inflammation detected by ultrasound (US) or magnetic resonance imaging (MRI). Developing RA according to the 2010 EULAR/ACR criteria within 1 year was a secondary outcome. A set of validated risk stratification criteria was developed. Results Using data from 2,293 symptomatic at-risk individuals, a stratification method was derived consisting of 6 clinical and serologic variables (morning stiffness, patient-reported joint swelling, difficulty making a fist, C-reactive protein, rheumatoid factor, and anti-citrullinated peptide antibody) yielding an area under the curve (AUC) of 0.80 (95% confidence interval [CI] 0.77-0.83) for IA development. The inclusion of US variables did not increase the discriminative ability. When MRI-detected subclinical inflammation variables were included, the AUC was 0.87 (95% CI 0.82-0.90). In the presence of clinical, serologic, and MRI variables, a sensitivity and specificity of >75% was achieved. For RA development, the AUC of the criteria with MRI was 0.93 (95% CI 0.90-0.97). Conclusions EULAR/ACR risk stratification criteria have been developed for people with arthralgia in secondary care who are considered at risk for RA. The criteria can be applied in the absence or presence of imaging data and have been developed to define homogeneous risk groups for future prevention trials.

Background Rheumatoid arthritis is a chronic disease of immune dysregulation affecting 1% of United Kingdom adults at an estimated cost to the taxpayer exceeding £5B per annum. Recently, enhanced pathophysiological understanding and a growing array of rational therapeutic candidates have converged on the potential to intercept rheumatoid arthritis before clinically manifest arthritis occurs, raising the possibility of delaying or even preventing disease. The National Institute for Health and Care Research Efficacy and Mechanism Evaluation Acceleration Award provided 12-month support to accelerate the development of an international precision medicine platform study, within remit of the Medical Research Council-National Institute for Health and Care Research Efficacy and Mechanism Evaluation Programme. To this end, Rheumatoid Arthritis Prevention: catalysing PlatfORm Trial proposed a pan-European precision medicine platform trial for preventative interventions in people at risk of rheumatoid arthritis. Challenges of delivering a trial of this nature led by a United Kingdom Sponsor, as well as those specific to the delivery of Rheumatoid Arthritis Prevention: catalysing PlatfORm Trial, were addressed. Objectives The overarching aim of Rheumatoid Arthritis Prevention: catalysing PlatfORm Trial was to submit a stage 1 application for the Efficacy and Mechanism Evaluation call: 23/15 precision medicine platform studies to efficiently evaluate the efficacy of interventions. In delivering this, we met the following objectives: Understand optimal sponsorship, governance and funding models for international platform trials by synthesising relevant literature in the form of systematic review. Convene and engage an international at risk of rheumatoid arthritis Precision Platform Trial Management Group with expertise in the pathobiological understanding and therapeutic management of at risk of rheumatoid arthritis, as well as the design and delivery of interception trials, with a view to developing a master protocol. Convene and consult a Rheumatoid Arthritis Prevention: catalysing PlatfORm Trial Public Advisory Group to directly inform trial design, including a strategy for mapping the level of rheumatoid arthritis progression risk to lifestyle and/or pharmacological interventions. Identify interventions to be evaluated in a platform trial, engaging appropriately with industry partners. Identify optimal clinical and/or immunological biomarkers for participant stratification. Outcomes Five work streams were set up to target delivery of the aforementioned objectives. A systematic review entitled ‘Operational complexities in international clinical trials: a systematic review of challenges and proposed solutions’ has been registered with the Open Science Framework, completed and submitted for publication. Linked to this, a working group was established to identify barriers and solutions to acting as Sponsor for Rheumatoid Arthritis Prevention: catalysing PlatfORm Trial; purposeful interactions with European Union and United Kingdom partner sites helped prioritise governance and funding models to enable delivery, and have informed local standard operating procedures for sponsoring international trials. A patient and public involvement Advisory group was formed, and a series of events and programme of work undertaken to feed into all aspects of Rheumatoid Arthritis Prevention: catalysing PlatfORm Trial. A range of potential interventions, non-pharmacological and pharmacological, were considered and prioritised for inclusion in Rheumatoid Arthritis Prevention: catalysing PlatfORm Trial’s design. A funding framework supported by industry partners, incorporating one lifestyle and two drug interventions, was developed, along with a strategy for prioritising future interventions. A working group was furthermore convened for the management of biological samples to be collected for research in biomarker evaluations. A stage 1 application for the 23/15 Efficacy and Mechanism Evaluation call was submitted in May 2023. Limitations In its first iteration, the substantive clinical trial proposal proposed as a result of the Accelerator award reported herein was not funded by National Institute for Health and Care Research. In part this was due to the approach adopted to address the ‘precision medicine’ element of the brief. Other challenges include the assembly of geographically diverse patient partners for an international study given time constraints, and logistical complexity in international trial design. Future work Efforts to fund the work described in amended form are ongoing. Funding This article presents independent research funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation programme as award number NIHR153955. Plain language summary Rheumatoid arthritis is a common long-term condition in which the immune system causes joint damage, leading to pain and reduced well-being. Some people who develop musculoskeletal pain and are found to have abnormalities in their immune systems on blood testing are at increased risk of rheumatoid arthritis. Researchers suspect certain treatments could relieve their symptoms and prevent them from developing the disease. This could have major benefits for society. A few clinical trials have tried to test whether taking certain drugs for a limited period might delay or prevent rheumatoid arthritis. However, it can prove difficult to find enough participants from routine rheumatology clinics to carry out such studies. In addition, people’s risk of developing rheumatoid arthritis varies: a person at slightly increased risk might not want a drug that could cause side effects, but a person at very high risk might. More ‘personalised’ trial designs are therefore needed. The National Institute for Health and Care Research Efficacy and Mechanism Evaluation Acceleration Award provided 12 months of support to address these challenges. We proposed a Newcastle-led, international ‘platform trial’. In platform trials, different treatments can be tested in different sections (arms) of a single trial. Treatments can be added or removed as results come in, without needing to start up a new trial each time. In Rheumatoid Arthritis Prevention: catalysing PlatfORm Trial, an international team came together, including experts in trial design and people with lived experience of being at risk of rheumatoid arthritis and/or trial participation. Working with partners in the pharmaceutical industry, we submitted a National Institute for Health and Care Research proposal. In it, we wanted to test a non-drug treatment in a ‘low-risk’ arm (for people at only slightly increased risk of rheumatoid arthritis), and a drug treatment in the ‘high-risk’ arm, for those at higher risk. The ultimate aim was to bring about a step change in the management of rheumatoid arthritis that recognises prevention is better than cure.

OBJECTIVES:The field of rheumatoid arthritis (RA) is moving towards identification of and intervention in people at risk of RA, but a validated risk stratification method is lacking. This work was undertaken to develop a risk stratification method for persons presenting with arthralgia considered to be at risk of RA. METHODS:A joint European Alliance of Associations for Rheumatology (EULAR)/American College of Rheumatology (ACR) expert committee was established. Risk factor and outcome data from 10 arthralgia cohorts (including clinically suspect arthralgia and autoantibody-positive arthralgia) were studied. The work focused on differentiating the risk of progression to clinically apparent inflammatory arthritis (IA) within 1 year, using clinical and serologic variables, without and with subclinical joint inflammation detected by ultrasound (US) or magnetic resonance imaging (MRI). Developing RA according to the 2010 EULAR/ACR criteria within 1 year was a secondary outcome. A set of validated risk stratification criteria was developed. RESULTS:Using data from 2293 symptomatic at-risk individuals, a stratification method was derived consisting of 6 clinical and serologic variables (morning stiffness, patient-reported joint swelling, difficulty making a fist, C-reactive protein, rheumatoid factor, and anti-citrullinated peptide antibody) yielding an area under the curve (AUC) of 0.80 (95% CI, 0.77-0.83) for IA development. The inclusion of US variables did not increase the discriminative ability. When MRI-detected subclinical inflammation variables were included, the AUC was 0.87 (95% CI, 0.82-0.90). In the presence of clinical, serologic, and MRI variables, a sensitivity and specificity of >75% was achieved. For RA development, the AUC of the criteria with MRI was 0.93 (95% CI, 0.90-0.97). CONCLUSIONS:EULAR/ACR risk stratification criteria have been developed for people with arthralgia in secondary care who are considered at risk for RA. They can be applied in the absence or presence of imaging data and have been developed to define homogeneous risk groups for future prevention trials.

Introduction The pharmacological management of inflammatory arthritis often requires choices that involve trade-offs between benefits, risks and other attributes such as administration route, frequency and cost. This living systematic review aims to inform international clinical guidelines on inflammatory arthritis by creating an evidence map of patient preference studies concerning the trade-offs in pharmacological management of inflammatory arthritis.Methods and analysis We will include published and peer-reviewed full-text studies in any language that quantitatively assess preferences of patients for the pharmacological management of inflammatory arthritis (rheumatoid arthritis, spondyloarthritis and juvenile idiopathic arthritis). Studies must use either stated or revealed preference methods to assess preferences and provide a quantitative assessment of relevant characteristics, such as benefits, risks, costs and process attributes. Articles will identified through Medline and EMBASE database searches from inception using search terms that combine keywords and subject headings for inflammatory arthritis and preference-based methods, and a search in the Health Preference Study and Technology Registry using keywords for the populations of interest. Two independent reviewers will perform abstract and full-text screening. Risk of bias will be assessed using the GRADE risk of bias tool. An evidence map will be generated to summarise included studies and their assessments of each trade-off. The search will be conducted every 6 months with new studies added to the inventory.Ethics and dissemination Ethics approval is not required. Results from the base review will be published in a peer-reviewed journal and findings will be presented at conferences. In the living model, we will publish updates and datasets on an Open Science Framework page, with periodic updates in peer-reviewed journals.

Background The way potential benefits and harms of trial interventions are shared within patient information leaflets (PILs) varies widely and may cause unnecessary harms ("nocebo effects"). The aim of this meta-analysis will be to evaluate the influence on recruitment rates and early effects on patient reported adverse events of principled patient information leaflets (PrinciPILs) compared with standard PILs. Methods Eligible studies will include those that report the effects on recruitment and patient reported adverse events of PrinciPILs compared to standard PILs. We will include in this meta-analysis all the standard PILs in studies within trials (SWATs) of PrinciPILs that were developed as part of the Medical Research Council (MRC) funded PrinciPIL project. By publishing this as a living meta-analysis, we will allow the meta-analysis to be updated with future SWATs of PrinciPILs. We will use the Cochrane Risk of Bias tool to evaluate the risk of bias for each outcome. We will report the total number of studies and participants analysed and the characteristics of included studies (including details of intervention, comparators, outcomes). For dichotomous data, we will calculate the risk difference and the risk ratio (RR) and 95% confidence intervals (CIs). For continuous outcomes we will use weighted mean differences with 95% CIs or standardized mean differences with 95% CIs. We will investigate heterogeneity by visually inspecting the forest plot and by considering the I2 test result. We will assess the certainty warranted for each outcome using the Grading of Recommendations Assessment Development and Evaluation (GRADE). Ethics approval is not applicable since no original data will be collected. The results will be disseminated through peer-reviewed publication and conference presentations. Discussion We will discuss the limitations of the meta-analysis including study risk of bias, inconsistency, heterogeneity, and imprecision. A general interpretation of the results and important implications will be provided.

Background When selecting samples for patient preference studies, it may be difficult or impractical to recruit participants who are eligible for a particular treatment decision. However, a general public sample may not be an appropriate proxy. Objective This study compares preferences for rheumatoid arthritis (RA) preventive treatments between members of the general public and first-degree relatives (FDRs) of confirmed RA patients to assess whether a sample of the general public can be used as a proxy for FDRs. Methods Participants were asked to imagine they were experiencing arthralgia and had screening tests indicating a 60% chance of developing RA within 2 yrs. Using a discrete choice experiment, participants were offered a series of choices between no treatment and 2 unlabeled hypothetical treatments to reduce the risk of RA. To assess data quality, time to complete survey sections and comprehension questions were assessed. A random parameter logit model was used to obtain attribute-level estimates, which were used to calculate relative importance, maximum acceptable risk (MAR), and market shares of hypothetical preventive treatments. Results The FDR sample ( n = 298) spent more time completing the survey and performed better on comprehension questions compared with the general public sample ( n = 982). The relative importance ranking was similar between the general public and FDR participant samples; however, other relative preference measures involving weights including MARs and market share differed between groups, with FDRs having numerically higher MARs. Conclusion In the context of RA prevention, the general public (average risk) may be a reasonable proxy for a more at-risk sample (FDRs) for overall relative importance ranking but not weights. The rationale for a proxy sample should be clearly justified. Highlights Participants from the general public were compared to first-degree relatives on their preferences for rheumatoid arthritis (RA) preventive treatments using a discrete choice experiment. Preferences were similar between groups in terms of the most important and least important attributes of preventive treatments, with effectiveness being the most important attribute. However, relative weights differed. Attention to the survey and predicted market shares of hypothetical RA preventive treatments differed between the general public and first-degree relatives. The general public may be a reasonable proxy for an at-risk group for patient preferences ranks but not weights in the disease prevention context; however, care should be taken in sample selection for patient preference studies when choosing nonpatients.

BACKGROUND:Since the publication of the 2011 European Alliance of Associations for Rheumatology (EULAR) recommendations for patient research partner (PRP) involvement in rheumatology research, the role of PRPs has evolved considerably. Therefore, an update of the 2011 recommendations was deemed necessary. METHODS:In accordance with the EULAR Standardised Operational Procedures, a task force comprising 13 researchers, 2 health professionals and 10 PRPs was convened. The process included an online task force meeting, a systematic literature review and an in-person second task force meeting to formulate overarching principles (OAPs) and recommendations. The level of agreement of task force members was assessed anonymously (0-10 scale). RESULTS:The task force developed five new OAPs, updated seven existing recommendations and formulated three new recommendations. The OAPs address the definition of a PRP, the contribution of PRPs, the role of informal caregivers, the added value of PRPs and the importance of trust and communication in collaborative research efforts. The recommendations address the research type and phases of PRP involvement, the recommended number of PRPs per project, the support necessary for PRPs, training of PRPs and acknowledgement of PRP contributions. New recommendations concern the benefits of support and guidance for researchers, the need for regular evaluation of the patient-researcher collaboration and the role of a designated coordinator to facilitate collaboration. Agreements within the task force were high and ranged between 9.16 and 9.96. CONCLUSION:The updated EULAR recommendations for PRP involvement are more substantially based on evidence. Together with added OAPs, they should serve as a guide for researchers and PRPs and will ultimately strengthen the involvement of PRPs in rheumatology research.

Background: About 20% of psoriasis (PsO) patients develop psoriatic arthritis (PsA) [1]. Several risk factors have been identified and current research projects are aiming to quantify individual risk of developing PsA for PsO patients. There has been a lot of research interest into the potential for intervening to reduce the risk of PsA in people at-risk. However, prior to designing such studies, it is crucial to examine the patient perspective considering the acceptability of interventions with different levels of arthritis risk and different side effects. Objectives: We aimed to investigate: a) the minimally accepted level of risk reduction for PsA development that would be needed from the perspective of PsO patients to consider preventive interventions; and b) to explore the maximal acceptable risk of side effects for a hypothetical preventive intervention. Methods: Adult PsO patients without PsA in the United Kingdom and the Netherlands were recruited via national PsO patient charities to take part in an online survey. Participants were randomly allocated to a questionnaire with a hypothetical baseline risk of developing PsA of 50%, 70% or 90%. All participants went through the same introduction with explanation and an example question. We used a probabilistic threshold technique to investigate the PsO patients' preferences for interventions to prevent PsA, in which they chose between no treatment (no benefit and no risks) or a preventive intervention (pharmacological treatment or lifestyle intervention). Treatment attributes included the chance of mild, moderate and severe side effects, of which participants made a series of choices to find the maximum level of risk at which they would accept the intervention. Subgroup differences were analysed using the Fisher-Freeman-Halton Exact Test. Results: Between November 9th 2022 and November 14th 2023, 285 PsO patients initiated the survey. 155 participants completed the survey, but 46 of these only completed the sections up to moderate side effects. Mean age was 46.8 (SD 15.3) and 76% were female. 68% had a diagnosis of PsO for >10 years and 28% had a first degree relative with PsA. 25% used tablets or injections as treatment for PsO. 143 out of 155 participants (92%) would consider a preventive pharmacological intervention to lower the risk of development of PsA. Overall, the maximum acceptable risk of developing PsA after initiating a hypothetical preventive therapy was on average 45% (IQR 30-50%). The acceptable risk was lower in the subgroup of PsO patients with a 50% baseline risk of developing PsA. See Figure 1. Participants were even more willing to start lifestyle interventions to lower their risk of developing PsA. A risk of developing PsA after lifestyle interventions of ≥30% was accepted by 89% of participants. The maximum accepted risk of mild side effects was on average 30% (IQR 20-50%), with a slightly lower acceptable risk level in the subgroup with a baseline risk of 50%. The maximum accepted risk of moderate side effects was on average 25% (IQR 10-40%), with no difference between subgroups. See Figure 2. We also found an overall tendency to accept severe side effects. Two third of the participants were willing to accept a risk of severe side effects of 10 in 100.000 patients. Conclusion: The willingness of PsO patients to start therapy to prevent PsA in our study is higher than previous results found for healthy people at risk of developing rheumatoid arthritis and axial spondyloarthritis [2]. This study provides a support for the acceptability of a clinical trial to prevent PsA in PsO patients when improved risk profiling becomes available, as many patients showed willingness to start preventive interventions even if these would come with a risk of side effects. REFERENCES: [1] Zabotti et al. Rheumatol Ther. 2021;8(4):1519-1534. [2] Van Boheemen et al. Arthritis Res Ther. 2020;22(1):217. Acknowledgements: This work is partly funded by HIPPOCRATES which received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No. 101007757. The JU receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA. Disclosure of Interests: None declared.

Abstract Background The value of patient and public involvement (PPI) during the earliest stages of clinical trial development, and prior to the award of substantive funding, is widely recognised. However, it is often under-resourced and PPI processes during this phase are rarely reported in detail. Having benefitted from seed funding to develop an international clinical trial proposal, we sought to describe and appraise PPI activities and processes that support pre-award co-development. Methods A 12-month “accelerator” award facilitated development of a substantive funding application to deliver the Rheumatoid Arthritis Prevention PlatfORm Trial (RAPPORT), conceived to prioritise preventative interventions for people at risk of RA. PPI partners, including individuals at risk of rheumatoid arthritis (RA), RA patients, relatives and members of the public, provided feedback on key trial design issues through online meetings, a feedback form and emails. PPI processes employed during the one-year accelerator project were thereafter evaluated by PPI partners using an anonymous online feedback form with reference to National Institute of Health and Care Research (NIHR) UK standards for public involvement in research. Results Sixteen out of the 25-strong PPI partner panel completed an online feedback form (64%). Respondents perceived PPI processes positively in relation to all NIHR standard domains. Several key facilitators and challenges were identified, including the need for adequate PPI funding during pre-award phases of research, strategies for creating an inclusive environment, flexibility around levels of involvement, and challenges in achieving representatively diverse participation, and the importance of communicating transparent processes for role-assignment and time-reimbursement. Conclusions In general, RAPPORT was considered an example of PPI well done, and in line with UK standards for public involvement in research. Facilitators and challenges of relevance for the development of future translational and clinical trial funding applications are highlighted.

Abstract Background Rheumatoid arthritis (RA) is often preceded by symptomatic phases during which classification criteria are not fulfilled. The health burden of these “at-risk” stages is not well described. This study assessed health-related quality of life (HRQoL), function, fatigue and depression in newly presenting patients with clinically suspect arthralgia (CSA), unclassified arthritis (UA) or RA. Methods Cross-sectional analysis of baseline Patient-Reported Outcome Measures (PROMs) was conducted in patients from the Birmingham Early Arthritis Cohort. HRQoL, function, depression and fatigue at presentation were assessed using EQ-5D, HAQ-DI, PHQ-9 and FACIT-F. PROMs were compared across CSA, UA and RA and with population averages from the HSE with descriptive statistics. Multivariate linear regression assessed associations between PROMs and clinical and sociodemographic variables. Results Of 838 patients included in the analysis, 484 had RA, 200 had CSA and 154 had UA. Patients with RA reported worse outcomes for all PROMs than those with CSA or UA. However, “mean EQ-5D utilities were 0.65 (95%CI: 0.61 to 0.69) in CSA, 0.61 (0.56 to 0.66) in UA and 0.47 (0.44 to 0.50) in RA, which was lower than in general and older (≥ 65 years) background populations.” In patients with CSA or UA, HRQoL was comparable to chronic conditions such as heart failure, severe COPD or mild angina. Higher BMI and older age (≥ 60 years) predicted worse depression (PHQ-9: -2.47 (-3.85 to -1.09), P < 0.001) and fatigue (FACIT-F: 5.05 (2.37 to 7.73), P < 0.001). Women were more likely to report worse function (HAQ-DI: 0.13 (0.03 to 0.21), P = 0.01) and fatigue (FACIT-F: -3.64 (-5.59 to -1.70), P < 0.001), and residents of more deprived areas experienced decreased function (HAQ-DI: 0.23 (0.10 to 0.36), P = 0.001), greater depression (PHQ-9: 1.89 (0.59 to 3.18), P = 0.004) and fatigue (FACIT-F: -2.60 (-5.11 to 0.09), P = 0.04). After adjustments for confounding factors, diagnostic category was not associated with PROMs, but disease activity and polypharmacy were associated with poorer performance across all PROMs. Conclusions Patient-reported outcomes were associated with disease activity and sociodemographic characteristics. Patients presenting with RA reported a higher health burden than those with CSA or UA, however HRQoL in the pre-RA groups was significantly lower than population averages.

Background Rheumatoid Arthritis (RA) is a chronic rheumatological condition which causes inflammation of both the joint lining and extra-articular sites. It affects around 1% of the UK population and, if not properly treated, can lead joint damage, disability, and significant socioeconomic burden. The risk of long-term damage is reduced if treatment is started in an early disease stage with treatment in the first 3 months being associated with significantly improved clinical outcomes. However, treatment is often delayed due to long referral waits and challenges in identifying early RA in primary care. We plan to use large primary care datasets to develop and validate an RA risk prediction model for use in primary care, with the aim to provide an additional mechanism for early diagnosis and referral for treatment. Methods We identified candidate predictors from literature review, expert clinical opinion, and patient research partner input. Using coded primary care data held in Clinical Practice Research Datalink (CPRD) Aurum, we will use a time to event Cox proportional hazards model to develop a 1-year risk prediction model for RA. This will be validated first in CPRD GOLD and then independently in the Secure Anonymised Information Linkage dataset. We will also conduct a sensitivity analysis for the same model at 2–5-year risk, with a secondary outcome of RA and initiation of a disease modifying drug, and with the addition of laboratory test results as candidate predictors. Discussion The resulting risk prediction model may provide an additional mechanism to distinguish early RA in primary care and reduce treatment delays through earlier referral. ### Competing Interest Statement JSC and KN are co-directors of DExtER operating division which is part of the University of Birmingham. DExtER operating division supports the extraction and preparing of healthcare data to support epidemiological analyses such as those seen in this article. ### Funding Statement BH is funded by an MB-PhD studentship supported by The Kennedy Trust for Rheumatology Research [grant no. KENN 2021 04]. NIHR Research for Patient Benefit funds the Development and validation of Rheumatoid Arthritis PredIction moDel using primary care health records (RAPID), grant NIHR203621. AD is funded by a PhD studentship from the Applied Research Collaboration Northwest, in turn funded by the National Institute for Health Research (NIHR). KR, KN and NJA are supported by the NIHR Birmingham Biomedical Research Centre (BRC). This is independent research carried out at the NIHR BRC. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. CM is part funded by the NIHR ARC West Midlands and the NIHR School for Primary Care Research ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: CPRD obtains annual research ethics approval from the UKs Health Research Authority Research Ethics Committee (East Midlands, Derby; reference no.05/MRE04/87) to receive and supply patient data for research. Therefore, no additional ethics approval is required for studies using CPRD data for research, subject to individual research protocols meeting CPRD data governance requirements. The use of CPRD data for the study was approved by the CPRD Independent Scientific Advisory Committee (reference no. 22_002239). Individual patient data is available from CPRD with valid license. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data access will be subject to ethics approval from CPRD.

Objective Some immunomodulatory drugs have been shown to delay the onset of, or lower the risk of developing, rheumatoid arthritis (RA), if given to individuals at risk. Several trials are ongoing in this area; however, little evidence is currently available about the views of those at risk of RA regarding preventive treatment. Method Three focus groups and three interviews explored factors that are relevant to first degree relatives (FDRs) of RA patients and members of the general public when considering taking preventive treatment for RA. The semi-structured qualitative interview prompts explored participant responses to hypothetical attributes of preventive RA medicines. Transcripts of focus group/interview proceedings were inductively coded and analysed using a framework approach. Results Twenty-one individuals (five FDRs, 16 members of the general public) took part in the study. Ten broad themes were identified describing factors that participants felt would influence their decisions about whether to take preventive treatment if they were at increased risk of RA. These related either directly to features of the specific treatment or to other factors, including personal characteristics, attitude towards taking medication, and an individual’s actual risk of developing RA. Conclusion This research highlights the importance of non-treatment factors in the decision-making process around preventive treatments, and will inform recruitment to clinical trials as well as information to support shared decision making by those considering preventive treatment. Studies of treatment preferences in individuals with a confirmed high risk of RA would further inform clinical trial design.

Objective We aimed to empirically compare maximum acceptable risk results estimated using both a discrete choice experiment (DCE) and a probabilistic threshold technique (PTT). Methods Members of the UK general public ( n = 982) completed an online survey including a DCE and a PTT (in random order) measuring their preferences for preventative treatment for rheumatoid arthritis. For the DCE, a Bayesian D-efficient design consisting of four blocks of 15 choice tasks was constructed including six attributes with varying levels. The PTT used identical risk and benefit attributes. For the DCE, a panel mixed-logit model was conducted, both mean and individual estimates were used to calculate maximum acceptable risk. For the PTT, interval regression was used to calculate maximum acceptable risk. Perceived complexity of the choice tasks and preference heterogeneity were investigated for both methods. Results Maximum acceptable risk confidence intervals of both methods overlapped for serious infection and serious side effects but not for mild side effects (maximum acceptable risk was 32.7 percent-points lower in the PTT). Although, both DCE and PTT tasks overall were considered easy or very easy to understand and answer, significantly more respondents rated the DCE choice tasks as easier to understand compared with those who rated the PTT as easier (7-percentage point difference; p < 0.05). Conclusions Maximum acceptable risk estimate confidence intervals based on a DCE and a PTT overlapped for two out of the three included risk attributes. More respondents rated the DCE as easier to understand. This may suggest that the DCE is better suited in studies estimating maximum acceptable risk for multiple risk attributes of differing severity, while the PTT may be better suited when measuring heterogeneity in maximum acceptable risk estimates or when investigating one or more serious adverse events.

First-degree relatives (FDRs) of people with rheumatoid arthritis (RA) are increasingly recruited to prediction and prevention studies. Access to FDRs is usually via their proband with RA. Quantitative data on predictors of family risk communication are lacking. RA patients completed a questionnaire assessing likelihood of commu-nicating RA risk information to their FDRs, demographic variables, disease impact, illness perceptions, autonomy preferences, interest in FDRs taking a predictive test for RA, dispositional openness, family functioning, and attitudes towards predictive testing. Ordinal regression examined associations between patients' characteristics and their median likelihood of communicating RA risk to FDRs. Questionnaires were completed by 482 patients. The majority (75.1%) were likely/extremely likely to communicate RA risk information to FDRs, especially their children. Decision-making preferences, interest in FDRs taking a predictive test, and beliefs that risk knowledge would increase people's empowerment over their health increased patients' odds of being likely to communicate RA risk information to FDRs. Beliefs that risk information would cause stress to their relatives decreased odds that patients would be likely to communicate RA risk. These findings will inform the development of resources to support family communication about RA risk.

Abstract Background/Aims There is an increasing interest in treating individuals at risk of rheumatoid arthritis (RA) with preventive drugs and several clinical trials have already reported results. Once developed, a successful predictive and preventive strategy needs to be integrated in the healthcare system. The current research explores the perceptions of health care professionals (HCPs) regarding this, and factors that may affect this integration. Methods We conducted one-to-one semi-structured qualitative interviews (either face-to-face or by telephone) with HCPs based in the West Midlands (UK). Audio recordings of the interviews were transcribed, coded and the data were analysed by thematic analysis facilitated by NVIVO. Results Nineteen HCPs (11 female, 8 male) were interviewed, including ten GPs, six rheumatologists and three rheumatology nurse specialists. The coding and thematic analysis of the transcripts identified four organising themes: Attributes of predictive and preventive approaches; Ethical and psychological concerns; Implementation issues; and Learning from management of other conditions. Theme 1 described necessary attributes of predictive and preventive approaches that interviewees highlighted, including the type and performance of the predictive test, the need for a clear evidence base for preventive approaches and consideration of the risks and benefits associated with the preventive treatment. Theme 2 described the ethical and psycho-social concerns that interviewees raised, including the potential negative economic, financial and psychological effects of risk disclosure for ‘at-risk' individuals and uncertainty around the development of RA and the potential for benefit associated with the treatments being considered. Theme 3 describes the implementation issues HCPs considered, including knowledge and training needs, the costs and resource implications of implementing predictive testing and preventive treatment, the role of different types of HCPs, guidelines and tools needed for implementation and patient characteristics, such as age and family history on appropriateness of prescribing preventive treatments. Theme 4 related to the lessons that could be learned from interviewees’ experiences of prediction and prevention in other disease areas, including relevant knowledge, of how preventive treatment is prescribed, existing guidelines and tools for other diseases which could be adapted for RA prevention and issues relating to risk communication. Conclusion For the successful implementation of predictive and preventative approaches in RA, HCPs across primary and secondary care need appropriate training about predictive tests, test interpretation, communication of results to at-risk individuals, and intervention options. Evidence of cost-efficiency, appropriate resource allocation, adaptation of official guidelines and careful consideration of the at-risk individuals’ psycho-social needs are also needed. Disclosure G. Simons: None. I. Wells: None. J.P. Kanacherril: None. C.D. Mallen: Grants/research support; CM is funded by the NIHR School for Primary Care Research and the NIHR ARC West Midlands. K. Raza: Grants/research support; K.R. is supported by the National Institute for Health Research Birmingham Biomedical Research Centre. M. Falahee: None.