Search

BackgroundThere 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.ObjectivesTo quantify FDRs’ preferences for preventive treatments for RA.MethodsAdult 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 levelsAttributeLevelsChance of developing RA reduced from 60% to10%; 20%; 30%; 40%How the treatment is takenA shallow injection under the skinA drip into the veinOne or two tabletsHow often the medication has to be takenDailyWeeklyMonthlyEvery 6 monthsChance of mild side effects2%; 5%; 10%Chance of a serious infection due to treatment0%; 1%; 5%Chance of a serious side effect that is potentially irreversible1 in 100,000 people20 in 100,000 people100 in 100,000 peopleResults356 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%.ConclusionEffective 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.AcknowledgementsOn 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 InterestsGwenda 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

BackgroundRisk of rheumatoid arthritis (RA) is 3-5 times higher in first-degree relatives (FDRs). Efforts are increasing to develop preventive interventions for this at risk group. Risk perception is a key predictor of health behaviours, including FDRs’ interest in predictive testing1 and preventive intervention for RA. Effective risk communication is essential for RA prevention studies and clinical translation2.ObjectivesTo define variables associated with perceived risk of developing RA in FDRs of RA patients.MethodsRA patients attending outpatient clinics (West Midlands, UK) were asked to invite their FDRs to complete a cross-sectional printed survey. Patients were also invited to complete a survey. Unique survey numbers enabled linkage of FDR and proband responses. FDRs’ perceived absolute risk, comparative risk, experiential risk, and worry about risk were assessed using 5-point Likert scales. Predictor variables included demographics, the Single Item Literacy Screener, Brief Illness Perception Questionnaire, Brief Approach/Avoidance Coping Questionnaire, Life Orientation Test Revised and the Short Health Anxiety Inventory. Patient predictors of FDR perceived risk included demographics, time since RA diagnosis and Rheumatoid Arthritis Impact of Disease Score.Outcome measure responses were grouped into ‘low’ and ‘high’ for regression analyses. Univariable analysis used independent samples T-tests, chi-square tests and Mann-Whitney U Tests. Backwards stepwise 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. Paired data from 213 patients were available for 292 of these FDRs.The distributions of risk perception scores are shown in Figure 1. All measures of perceived risk were inter-correlated (p65.2% of FDRs perceived themselves to be ‘Likely’ or ‘Very Likely’ to develop RA in their lifetime. FDR’s ethnic group, deprivation index, employment status, education level, smoking status, cohabitation with index patient status, coping style and dispositional optimism were not significantly different between high and low perceived risk groups. Characteristics significant in univariable analyses were used in multivariable analyses (Table 1). Children were 3.89 times more likely than siblings to perceive themselves at high risk of RA. Higher health anxiety scores were associated with increased perceived risk. Female gender, and beliefs that RA would last a long time, and cause higher concern and negative emotional impact predicted increased risk perceptions. Higher perceptions of how well treatment would control RA was associated with a reduced likelihood of perceiving oneself at high risk.Index patient characteristics did not associate with FDRs’ risk perceptions.Table 1.Multivariable analysisFDR CharacteristicPerceived Risk [Odds Ratio (95% Confidence Interval)]AbsoluteComparativeExperientialWorry about RiskGender1.98 (1.19-3.27)* Male$ FemaleRelationship to index patient2.80 (1.70-4.61)***3.43 (2.04-5.78)***3.89 (2.24-6.75)***2.26 (1.30-3.94)** Child Sibling$Health Literacy1.50 (1.00-2.25)Illness Perceptions0.89 (0.79-0.99)*1.25 (1.05-1.48)*1.17 (0.99-1.38)0.84 (0.74-0.94)** Timeline0.91 (0.81-1.01)0.87 (0.77-0.98)*1.36 (1.13-1.63)** Treatment control1.20 (1.02-1.40)* Concern EmotionHealth Anxiety1.04 (1.01-1.07)*1.05 (1.01-1.07)*1.07 (1.03-1.11)**1.06 (1.02-1.09)***p**p***p$ ReferenceConclusionFDRs’ 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 effective risk communication and preventive strategies.References[1]Wells et al. Rheumatology. 2021 doi: 10.1093/rheumatology/keab890[2]Mankia et al. Ann Rheum Dis. 2021;80(10):1286-98AcknowledgementsS. Bunnewell and I. Wells are joint first authors.Disclosure of InterestsNone declared

BackgroundThere 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.ObjectivesAssess the extent to which FDR characteristics and beliefs predict risk tolerances for preventive treatments.MethodsAdult 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 optionsTreatment attributeLevels describing no treatment optionLevels describing treatment optionChance of developing RA60%20%Chance of mild side effects0%2%; 4%; 5%; 7% or 10%Chance of a serious infection due to treatment0%1%; 1.5%; 2%; 3% or 5%Chance of a serious side effect that is potentially irreversible0%0.001%; 0.01%; 0.02%; 0.05% or 0.1%Results289 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.ConclusionAge 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.AcknowledgementsOn 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 InterestsGwenda 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.