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.

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.

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.

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.

Background There is increasing research interest in the development of preventive treatment for individuals at risk of rheumatoid arthritis (RA). Previous studies have explored the perceptions of at-risk groups and patients about predictive and preventive strategies for RA, but little is known about health care professionals’ (HCPs) perspectives. Methods One-to-one semi-structured qualitative interviews were conducted (face-to-face or by telephone) with HCPs. Audio recordings of the interviews were transcribed, and the data were analysed by thematic analysis. Results Nineteen HCPs (11 female) were interviewed, including ten GPs, six rheumatologists and three rheumatology nurse specialists. The thematic analysis identified four organising themes: 1) Attributes of predictive and preventive approaches; 2) Ethical and psychological concerns; 3) Implementation issues and 4) Learning from management of other conditions. Theme 1 described necessary attributes of predictive and preventive approaches, including the type and performance of predictive tools, the need for a sound evidence base and consideration of risks and benefits associated with 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, uncertainty around the development of RA and the potential for benefit associated with the treatments being considered. Theme 3 describes the implementation issues considered, including knowledge and training needs, costs and resource implications of implementing predictive and preventive approaches, the role of different types of HCPs, guidelines and tools needed, and patient characteristics relating to the appropriateness of preventive treatments. Theme 4 describes lessons that could be learned from interviewees’ experiences of prediction and prevention in other disease areas, including how preventive treatment is prescribed, existing guidelines and tools for other diseases and issues relating to risk communication. Conclusions For successful implementation of predictive and preventative approaches in RA, HCPs need appropriate training about use and interpretation of predictive tools, communication of results to at-risk individuals, and options for intervention. 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.

BACKGROUND:There is growing recognition of the importance of patient and public stakeholder involvement (PPI) in patient preference research. However, limited evidence exists regarding the impact, barriers and enablers of PPI in preference studies. The Innovative Medicines Initiative (IMI)-PREFER project conducted a series of preference case studies which incorporated PPI.OBJECTIVE:To describe: (1) how PPI was operationalized in the PREFER case studies, (2) the impact of PPI, and (3) factors that served to impede and facilitate PPI.METHODS:We reviewed the PREFER final study reports to determine how patient partners were involved. We conducted a thematic framework analysis to characterize the impact of PPI and then administered a questionnaire to the PREFER study leads to identify barriers and facilitators to effective PPI.RESULTS:Eight PREFER case studies involved patients as research partners. Patient partners were involved in activities spanning all phases of the patient preference research process, including in study design, conduct and dissemination. However, the type and degree of patient partner involvement varied considerably. Positive impacts of PPI included improvements in the: (1) quality of the research and research process; (2) patient partner empowerment; (3) study transparency and dissemination of results; (4) research ethics, and (5) trust and respect between the research team and the patient community. Of the 13 barriers identified, the 3 most frequently reported were inadequate resources, insufficient time to fully involve patient partners, and uncertainty regarding how to operationalize the role of 'patient partner. Among the 12 facilitators identified, the two most frequently cited were (1) having a clearly stated purpose for involving patients as research partners; and (2) having multiple patient partners involved in the study.CONCLUSION:PPI had many positive impacts on the PREFER studies. Preference study leads with prior PPI experience reported a greater number of positive impacts than those with no such experience. In light of the numerous barriers identified, multi-faceted implementation strategies should be considered to support adoption, integration and sustainment of PPI within preference research. Additional case studies of patient partner involvement in preference research are needed as well to inform best practices in this area.

Background While the integration of patient and public involvement (PPI) in clinical research is now widespread and recommended as standard practice, meaningful PPI in pre-clinical, discovery science research is more difficult to achieve. One potential way to address this is by integrating PPI into the training programmes of discovery science postgraduate doctoral students. This paper describes the development and formative evaluation of the Student Patient Alliance (SPA), a programme developed at the University of Birmingham that connects PPI partners with doctoral students. Methods Following a successful pilot of the SPA by the Rheumatology Research Group at the University of Birmingham, the scheme was implemented across several collaborating Versus Arthritis / Medical Research Council (MRC) centres of excellence. Doctoral students were partnered with PPI partners, provided with initial information and guidance, and then encouraged to work together on research and public engagement activities. After six months, students, their PPI partners and the PPI coordinators at each centre completed brief surveys about their participation in the SPA. Results Both doctoral students and their PPI partners felt that taking part in SPA had a positive impact on understanding, motivation and communication skills. Students reported an increased understanding of PPI and patient priorities and reported improved public engagement skills. Their PPI partners reported a positive impact of the collaboration with the students. They enjoyed learning about the student’s research and contributing to the student’s personal development. PPI coordinators also highlighted the benefits of the SPA, but noted some challenges they had experienced, such as difficulties matching students with PPI partners. Conclusions The SPA was valued by students and PPI partners, and it is likely that initiatives of this kind would enhance students’ PPI and public engagement skills and awareness of patients’ experiences on a wider scale. However, appropriate resources are needed at an institutional level to support the implementation of effective programmes of this kind on a larger scale.

Background Tests to predict the development of chronic diseases in those with a family history of the disease are becoming increasingly available and can identify those who may benefit most from preventive interventions. It is important to understand the acceptability of these predictive approaches to inform the development of tools to support decision making. Whilst data are lacking for many diseases, data are available for ischemic heart disease (IHD). Therefore, this study investigates the willingness of those with a family history of IHD to take a predictive test, and the effect of the test results on risk-related behaviours. Method Medline, EMBASE, PsycINFO, LILACS and grey literature were searched. Primary research, including adult participants with a family history of IHD, and assessing a predictive test were included. Qualitative and quantitative outcomes measuring willingness to take a predictive test and the effect of test results on risk-related behaviours were also included. Data concerning study aims, participants, design, predictive test, intervention and findings were extracted. Study quality was assessed using the Standard Quality Assessment Criteria for Evaluating Research Papers from a Variety of Fields and a narrative synthesis undertaken. Results Five quantitative and two qualitative studies were included. These were conducted in the Netherlands ( n = 1), Australia ( n = 1), USA ( n = 1) and the UK ( n = 4). Methodological quality ranged from moderate to good. Three studies found that most relatives were willing to take a predictive test, reporting family history ( n = 2) and general practitioner (GP) recommendation ( n = 1) as determinants of interest. Studies assessing the effect of test results on behavioural intentions ( n = 2) found increased intentions to engage in physical activity and smoking cessation, but not healthy eating in those at increased risk of developing IHD. In studies examining actual behaviour change ( n = 2) most participants reported engaging in at least one preventive behaviour, particularly medication adherence. Conclusion The results suggests that predictive approaches are acceptable to those with a family history of IHD and have a positive impact on health behaviours. Further studies are needed to provide a comprehensive understanding of predictive approaches in IHD and other chronic conditions.

Objectives To quantify tolerance to risks of preventive treatments among first-degree relatives (FDRs) of patients with rheumatoid arthritis (RA). Methods Preventive treatments for RA are under investigation. In a preference survey, adult FDRs assumed a 60% chance of developing RA within 2 years and made choices between no treatment and hypothetical preventive treatment options with a fixed level of benefit (reduction in chance of developing RA from 60% to 20%) and varying levels of risks. Using a probabilistic threshold technique, each risk was increased or decreased until participants switched their choice. Perceived risk of RA, health literacy, numeracy, Brief Illness Perception Questionnaire and Beliefs about Medicines Questionnaire-General were also assessed. Maximum acceptable risk (MAR) was summarised using descriptive statistics. Associations between MARs and participants’ characteristics were assessed using interval regression with effects coding. Results 289 FDRs (80 male) responded. The mean MAR for a 40% reduction in chance of developing RA was 29.08% risk of mild side effects, 9.09% risk of serious infection and 0.85% risk of a serious side effect. Participants aged over 60 years were less tolerant of serious infection risk (mean MAR ±2.06%) than younger participants. Risk of mild side effects was less acceptable to participants who perceived higher likelihood of developing RA (mean MAR ±3.34%) and more acceptable to those believing that if they developed RA it would last for a long time (mean MAR ±4.44%). Conclusions Age, perceived chance of developing RA and perceived duration of RA were associated with tolerance to some risks of preventive RA therapy.

BACKGROUND:There is increasing research focus on prediction and prevention of rheumatoid arthritis (RA). Information about risk of RA is increasingly available via direct-to-consumer testing. However, there is limited understanding of public perceptions around predictive testing for RA. This study explores public perceptions of predictive testing for RA in comparison to breast cancer (BC) and early-onset Alzheimer's disease (AD). METHODS:Four focus groups with 21 members of the public were conducted using hypothetical vignettes about predictive testing for each disease. Transcripts of focus group proceedings were analysed inductively using thematic analysis. RESULTS:Thematic analysis of the data produced three key themes: decision-making factors, consequences, and consumer needs. Factors suggested that might influence decision-making about predictive testing included family history, fear, and perceived severity and treatability of the illness. RA was perceived to be less severe and more treatable than BC/AD. Potential consequences of predictive testing across all diseases included lifestyle modification, planning for the future and discrimination by employers or insurers. Predictive testing for RA was perceived to have less potential for negative psychological consequences than other diseases. Participants highlighted that individuals undertaking predictive testing should be signposted to appropriate support services and receive information on the accuracy of predictive testing. It was suggested that strategies to mitigate concerns regarding communication and confidentiality of risk results are required. CONCLUSIONS:The findings of this study reflect public misunderstandings regarding RA that may impact the uptake of and responses to predictive testing, and key informational needs of individuals considering a predictive test. Predictive strategies should be accompanied by awareness-raising initiatives and informational resources.

Background There is a growing research focus on the development of interventions to reduce risk of rheumatoid arthritis (RA) in at-risk individuals.(1) A recent survey of the general population asked to assume a 60% risk of RA established that hypothetical preventive treatments were acceptable to most participants.(2) However the preferences of individuals who actually have an elevated risk of RA, such as first-degree relatives (FDRs) of RA patients, are not well understood. Objectives To quantify FDRs’ preferences for preventive treatments for RA. Methods Adult FDRs in the UK and Germany were invited to take part in a web-based survey via patients with clinician-confirmed RA either during a rheumatology clinic visit or by mail. In addition, FDRs taking part in a UK-based prospective cohort (PREVeNT-RA) were invited via email. Participants received information about RA followed by questions to check comprehension, and an introduction to the survey including warm-up questions. They were asked to imagine they were experiencing arthralgia and had positive autoantibody tests indicating a 60% chance of developing RA in the next two years. Using a discrete choice experiment, participants were offered a series of 15 choices between no treatment and two unlabeled hypothetical treatments to reduce risk of RA. Treatments were defined by six attributes with varying levels, describing benefits, risks, and frequency/route of administration (Table 1). Attribute selection and presentation was informed by qualitative research, ranking surveys, systematic literature review, and expert opinion. Survey layout was informed by patient research partners and qualitative pre-testing. A two-class latent class analysis was used to estimate preferences and calculate relative importance of treatment attributes and predicted uptake. A panel mixed logit model was used to obtain maximum acceptable risk estimates. Table 1. Treatment attributes and levels Attribute Levels Chance of developing RA reduced from 60% to 10%; 20%; 30%; 40% How the treatment is taken A shallow injection under the skin A drip into the vein One or two tablets How often the medication has to be taken Daily Weekly Monthly Every 6 months Chance of mild side effects 2%; 5%; 10% Chance of a serious infection due to treatment 0%; 1%; 5% Chance of a serious side effect that is potentially irreversible 1 in 100,000 people 20 in 100,000 people 100 in 100,000 people Results 356 FDRs (252 female, 289 in the UK) responded. While treatment effectiveness was the most important attribute in both classes (Figure 1), the importance of other attributes differed between classes, with method and frequency of treatment administration being more important in class 2 and risk of mild side effects only impacting treatment choice in class 1. Perceived risk of developing RA predicted class assignment; those with higher perceived risk were more likely to belong to class 1. On average, the predicted uptake of treatment profiles estimating prevention candidates: abatacept; atorvastatin; hydroxychloroquine; tolerogenic cell-based therapy; and no treatment would be 50%, 15%, 9%, 18% and 0%, respectively. Finally, the maximum acceptable risk participants were willing to accept were 81%, 25% and 3% point increases in risk of mild side effects, serious infection, and serious side effects, respectively, for medicines that would reduce their risk of developing RA in the upcoming two years from 60% to 20%. Conclusion Effective preventive treatments for RA were acceptable to FDRs asked to assume a 60% chance of developing RA. Mode and frequency of treatment administration had a greater impact on treatment choices for participants with a lower perceived risk of RA. These findings are informative for target product profile development, endpoint selection, benefit-risk assessment, regulatory approval, and development of informational resources for those at risk of RA. References [1]Mankia et al. Ann Rheum Dis. 2021;80(10):1286-98. [2]Simons et al. Ann Rheum Dis. 2021;80:96-7. Acknowledgements On behalf of the PREFER project. PREFER received funding from the IMI 2 Joint Undertaking (grant No. 115966), which receives support from the EU’s Horizon 2020 research and innovation program and European Federation of Pharmaceutical Industries and Associations (EFPIA). This abstract and its contents reflect the view of the presenter and not the view of PREFER, IMI, the European Union or EFPIA. K. Raza is supported by the NIHR Birmingham Biomedical Research Centre. Disclosure of Interests Gwenda Simons: None declared, Jorien Veldwijk: None declared, Rachael DiSantostefano Shareholder of: Johnson & Johnson, Employee of: Janssen Research and Development, Matthias Englbrecht Speakers bureau: Abbvie, Chugai, Eli Lilly, Novartis, Roche, Sanofi, Munidpharma, Paid instructor for: Abbvie, Chugai, Roche, Consultant of: Abbvie, Novartis, Roche, Sanofi, Grant/research support from: Roche, Chugai, Christine Radawski Shareholder of: Eli Lilly & Company, Employee of: Eli Lilly & Company, Larissa Valor: None declared, Jenny Humphreys: None declared, Ian N. Bruce: None declared, Karim Raza Consultant of: Abbvie, Sanofi, Grant/research support from: Bristol Myers Squibb, Marie Falahee: None declared

ObjectivesTo define variables associated with perceived risk of developing rheumatoid arthritis (RA) in first-degree relatives (FDRs) of patients with RA.MethodsPatients with RA and their FDRs were invited to complete cross-sectional surveys. FDR and index patient responses were linked. FDRs' perceived absolute risk, comparative risk, experiential risk and worry about risk were assessed using 5-point Likert scales. FDR predictor variables included demographics, illness perceptions and psychosocial variables. Patient predictors of FDR perceived risk were assessed. Binary logistic regression examined the relationship between FDR characteristics and perceived risk of RA. Generalised estimating equations assessed whether patient variables predicted FDR's perceived risk.Results396 FDRs returned a survey. 395 FDRs provided sufficient data and were included in analysis. Paired data from 213 patients were available for 291 of these FDRs. All measures of perceived risk were inter-correlated. 65.2% of FDRs perceived themselves to be 'likely' or 'very likely' to develop RA in their lifetime. Relationship with index patient, high health anxiety, female gender, long perceived RA duration, high perceived concern about RA, negative perceived emotional impact of RA and low perceptions of how well treatment would control RA were all associated with increased FDRs' perceived risk. Patient characteristics did not associate with FDRs' risk perceptions.ConclusionsFDRs' perceived risk of RA was high. Key predictors included being a child of a patient with RA, higher health anxiety and lower perceptions of RA treatment control. An understanding of these predictors will inform the development of tailored risk communication resources and preventive clinical strategies for RA.

Abstract Background Rheumatoid arthritis (RA) is a chronic inflammatory arthritis which can cause joint damage and reduced quality of life. Early treatment of RA within 3 months of symptom onset is associated with improved clinical outcomes. However, this window of opportunity is often missed. One important contributing factor is patients with symptoms of RA delaying consulting their general practitioner (GP). Previous research indicates that patients with inflammatory arthritis are likely to visit pharmacies for advice before consulting their GP. Therefore, pharmacists are well positioned to identify patients with symptoms of early inflammatory arthritis and signpost them appropriately. This research examines community pharmacy staff’s knowledge, perceptions, and approaches to management of patients presenting with symptoms of RA in order to identify training needs and other opportunities for intervention to enhance the role of pharmacy staff in the pathway to care. Methods Semi-structured interviews were conducted with 19 community pharmacy staff in the West Midlands (UK), during a 12-month period (2017–2018). The interviews were audio-recorded, transcribed, and analyzed using thematic analysis facilitated by NVivo 12. Results There was considerable variation in knowledge and perceptions of RA and the need for early treatment amongst pharmacists and other pharmacy staff. The potential role of pharmacists and other pharmacy staff in reducing delay in help-seeking was also discussed. Four themes emerged from thematic analysis: (1) Variations in perceptions and knowledge about RA. (2) The role of the pharmacy in increasing public awareness about RA. (3) The role of the pharmacy staff in facilitating access to the GP. (4) Practical considerations for pharmacy-based interventions. Conclusion Variability in knowledge and perceptions of RA amongst pharmacists, and amongst other pharmacy staff will affect effective signposting of suspected RA cases. This study identifies opportunities for enhanced training of community pharmacists and other pharmacy staff in relation to inflammatory arthritis as well as other pharmacy-based interventions, such as public awareness campaigns about RA and other musculoskeletal conditions. Together with existing referral services and other pharmacy-based initiatives this could result in enhanced signposting to GP consultation or other appropriate NHS services for inflammatory symptoms and reduced treatment delay.

Objective To quantify preferences for preventive therapies for rheumatoid arthritis (RA) across three countries. Methods A web-based survey including a discrete choice experiment was administered to adults recruited via survey panels in the UK, Germany and Romania. Participants were asked to assume they were experiencing arthralgia and had a 60% chance of developing RA in the next 2 years and completed 15 choices between no treatment and two hypothetical preventive treatments. Treatments were defined by six attributes (effectiveness, risks and frequency/route of administration) with varying levels. Participants also completed a choice task with fixed profiles reflecting subjective estimates of candidate preventive treatments. Latent class models (LCMs) were conducted and the relative importance of attributes, benefit-risk trade-offs and predicted treatment uptake was subsequently calculated. Results Completed surveys from 2959 participants were included in the analysis. Most participants preferred treatment over no treatment and valued treatment effectiveness to reduce risk more than other attributes. A five-class LCM best fitted the data. Country, perceived risk of RA, health literacy and numeracy predicted class membership probability. Overall, the maximum acceptable risk for a 40% reduction in the chance of getting RA (60% to 20%) was 21.7%, 19.1% and 2.2% for mild side effects, serious infection and serious side effects, respectively. Predicted uptake of profiles reflecting candidate prevention therapies differed across classes. Conclusion Effective preventive pharmacological treatments for RA were acceptable to most participants. The relative importance of treatment attributes and likely uptake of fixed treatment profiles were predicted by participant characteristics.

Background There is a growing research focus on the development of interventions to reduce risk of rheumatoid arthritis (RA) in at-risk groups.(1) RA patients’ first-degree relatives (FDRs) have an elevated risk of developing RA and are potential candidates for preventive interventions. Recent studies have quantified the preferences of at risk groups for preventive treatments.(2-4) Little is known about predictors of preference heterogeneity in this context. Objectives Assess the extent to which FDR characteristics and beliefs predict risk tolerances for preventive treatments. Methods Adult FDRs of patients with confirmed RA in the UK were invited to take part in a web-based survey. FDRs enrolled in a UK prospective cohort (PREVeNT-RA) were also invited. Survey development, including attribute selection and presentation, was informed by qualitative research, ranking surveys, literature review, and expert opinion including patient research partners. Respondents received information about RA, questions to check comprehension, and an introduction to the survey. Participants were asked to imagine they were experiencing arthralgia and had positive autoantibody tests indicating a 60% chance of developing RA within two years. Using a probabilistic threshold technique, participants made choices between no treatment (no benefit and no risks) or a preventive treatment option. Treatment options were defined by a fixed level of benefit (reduction in risk of RA from 60% to 20%) and varying levels of risks (Table 1). For each treatment risk, participants made a series of choices where the risk was systematically increased or decreased until they switched their choice. This procedure was repeated for each of the remaining risks. Participants also completed items assessing demographics, perceived risk of developing RA, health literacy, subjective numeracy, the Brief Illness Perception Questionnaire (IPQ) and the Beliefs about Medicines Questionnaire General (BMQ-G). The maximum acceptable risk (MAR) respondents were willing to accept for a 40% (60% to 20%) point risk reduction in developing RA was summarized across participants using descriptive statistics. Associations between MARs and participants’ characteristics and illness/medication beliefs were assessed using interval regression. Independent variables were dichotomized and effects coded. Table 1. Attributes and levels of treatment options Treatment attribute Levels describing no treatment option Levels describing treatment option Chance of developing RA 60% 20% Chance of mild side effects 0% 2%; 4%; 5%; 7% or 10% Chance of a serious infection due to treatment 0% 1%; 1.5%; 2%; 3% or 5% Chance of a serious side effect that is potentially irreversible 0% 0.001%; 0.01%; 0.02%; 0.05% or 0.1% Results 289 FDRs (80 male) responded. The mean (SE) MAR for mild side effects, serious infection, and serious side effects was 29.08 (1.52), 9.09 (0.60) and 0.85 (0.27), respectively. Participants aged over 60 years were less tolerant of risk of serious infection than average (mean MAR - 2.06 (0.78)) and younger participants were more tolerant of risk of serious infection than average (mean MAR + 2.06 (0.78)). Risk of mild side effects was less acceptable to participants who perceived they were likely/very likely to develop RA (mean MAR - 3.34 (1.55)) than to those who did not (mean MAR + 3.34 (1.55)). Education level, health literacy, numeracy, IPQ and BMQ-G subscales were not predictors of risk tolerance. Conclusion Age and perceived risk of RA had a significant impact on FDRs’ tolerance for specific, but not all, included risks. Cognitive ability and beliefs about RA/medicine did not explain preference heterogeneity. This is informative for drug development and the development of tailored risk communication resources to support preventive approaches. References [1]Mankia et al. Ann Rheum Dis. 2021;80(10):1286-98. [2]Simons et al. Ann Rheum Dis. 2021;80:96-7. [3]Harrison et al. Plos One. 2009; 14(4): e0216075. [4]Finckh et al. Curr Rheumatol Rep. 2016;18: 51. Acknowledgements On behalf of the PREFER project. PREFER received funding from the IMI 2 Joint Undertaking (grant No. 115966), which receives support from the EU’s Horizon 2020 research and innovation program and European Federation of Pharmaceutical Industries and Associations (EFPIA). K. Raza is supported by the NIHR Birmingham Biomedical Research Centre. Disclosure of Interests Gwenda Simons: None declared, Ellen Janssen Shareholder of: Johnson & Johnson, Employee of: Janssen Research and Development, Jorien Veldwijk: None declared, Rachael DiSantostefano Shareholder of: Johnson & Johnson, Employee of: Janssen Research and Development, Matthias Englbrecht Speakers bureau: Abbvie, Chugai, Eli Lilly, Novartis, Roche, Sanofi, Mundipharma, Paid instructor for: Abbvie, Chugai, Roche, Consultant of: Abbvie, Novartis, Roche, Sanofi, Grant/research support from: Roche, Chugai, Christine Radawski Shareholder of: Eli Lilly, Employee of: Eli Lilly, Larissa Valor: None declared, Jenny Humphreys: None declared, Ian N. Bruce: None declared, Brett Hauber Shareholder of: Pfizer Inc., Employee of: Pfizer Inc., Karim Raza Consultant of: Abbvie, Sanofi, Grant/research support from: Bristol Myers Squibb, Marie Falahee: None declared.