Abstract

Background:Accurate prediction of rheumatoid arthritis (RA) development in persons at risk of RA can help to select individuals for early intervention trials. Currently, RA prediction mostly relies on biomarkers such as genetic factors, autoantibodies and imaging abnormalities, with symptoms being only a minor component1-3. However, at-risk individuals exhibit a high prevalence of diverse and often severe symptoms4,5and information on the predictive ability of individual symptoms or symptom complexes is still largely lacking.Objectives:We investigated the prevalence and predictive ability of symptoms in persons at-risk of RA, using the validated ‘Symptoms in Persons At Risk of Rheumatoid Arthritis’ (SPARRA) questionnaire.Methods:Individuals at-risk of RA from four different cohorts from the Netherlands (n=122), United Kingdom (N=90), Sweden (N=13) and Switzerland (N=20), were asked to fill out the SPARRA questionnaire, consisting of 69 questions (previously described6). Individuals were either defined as persons with anticitrullinated protein antibodies (ACPA) and/or rheumatoid factor (RF; n=193), having relevant symptoms (i.e. clinically suspect arthralgia with or without RA-specific antibodies, n=70) or being first degree relatives (FDR, n=20) of RA patients. All were followed for a minimum of 24 months or until clinical arthritis development. Univariable analyses were performed for possible predictor selection (p<0.2), followed by stepwise forward selection (by Cox regression, p<0.1) to create a multivariable prediction model.Results:The mean age of all participants was 49 years and 69% was female. In total, 56 persons (23%) developed clinical arthritis (n=22, 25, 7, 2 respectively in the 4 groups) after a median of 11.9 months (IQR 5.3 - 17.8). In total, 23 SPARRA questions were selected from the univariable analyses and entered in the stepwise forward selection procedure. Time to development of RA was predicted by the following questions: pain moving from joint to joint, having moderate or severe swelling in joints, feeling ≥1 days fatigue per month and feeling stiffness in joints of one and both feet (table 1).Table 1.Multivariable prediction model of SPARRA questions to predict clinical arthritisHR (95% CI), pDoes your joint pain move from joint to joint?No; from arms to legs; from legs to arms (ref)1From ons side to the other2.96 (1.57; 5.57), p = 0.001Over the past month how much joint swelling have you had?None or mild (ref)1Moderate or severe3.04 (1.48; 6.25), p = 0.003Over the past month how many days of the month have you had fatigue?0 (ref)1≥ 10.32 (0.15; 0.67), p = 0.003Where did you feel joint stiffness?Neither feet (ref)One foot0.93 (0.42; 2.08), p = 0.865Both feet0.40 (0.17; 0.93), p = 0.032Conclusion:Asking persons at-risk of RA about joint pain, swelling and stiffness is common clinical practice. However, specific details such as pain moving from one side to the other or degree of joint swelling may provide useful additional information to estimate a person’s RA risk. The protective effect noted for fatigue and stiff feet may reflect an underlying pain syndrome rather than RA risk. We are currently performing analyses of the potential added value of SPARRA questions over the clinical prediction model by van der Stadt et al3which will help determine the final format of the SPARRA questionnaire.

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