Background/Purpose: A prospective study of preclinical SLE disease evolution is needed to help elucidate critical aspects of disease etiology and early pathogenesis, and to identify early directed therapeutic targets. However, designing the most informative study of this complex heterogeneous disease is unclear without better definition of high-risk populations. Our objective was to determine screening characteristics to identify individuals for follow-up in a prospective study.

Methods: We sent letters to 3823 individuals who reported having a family member with SLE and who did not meet ≥ 4 ACR criteria for SLE at their baseline visit to enroll in a follow-up study to gather information regarding interim development of signs and symptoms consistent with SLE; 436 enrolled. Fifty-six individuals had transitioned to SLE (> 4 cumulative ACR criteria, verified by medical record review) by the time of follow-up. Generalized estimating equations, accounting for correlation within families, assessed associations between our dichotomous outcome of transitioning to SLE with baseline characteristics, including age, sex, race, ANA positivity (ANA+), Connective Tissue Disease Screening Questionnaire (CSQ) SLE score, and number of ACR criteria. Predictive accuracy of characteristics on transitioning were analyzed using positive predictive value (PPV), negative predictive value (NPV), sensitivity, and specificity. Characteristics were separated by the amount of effort required to collect the data: questionnaire alone; questionnaire and a blood test; and a blood draw and medical records for ACR criteria confirmation.

Results: Age (47.2 vs 47.2 years), sex (87.5% vs 83.2%), and race (76.8% vs 73.4% European American (EA)) were similar between those who transitioned and those who did not transition. Sisters of a SLE proband were just as likely to transition as other first-degree relatives (OR=1.5, 95% CI 0.8-2.8), as were those <30 years of versus those ≥ 30 years old (OR=1.3, 95% Ci 0.5-3.2), and non-EAs versus EA (OR=1.3, 95% 0.5-3.5). ANA+, CSQ classification of possible or probable SLE (CSQ-SLE+), and greater number of ACR criteria were each associated with transitioning to SLE. Being ANA+ and having photosensitivity by confirmed ACR criteria had the highest PPV and specificity for transitioning to SLE (Table 1). CSQ-SLE+ had a better PPV, NPV, sensitivity and specificity than ANA+ alone. Combining ANA+ and CSQ-SLE+ increased the PPV and specificity of transitioning to SLE; additionally limiting to females did not increase the predictive accuracy.

Conclusion: Limiting follow-up to females or to a specific race/ethnic group does not appear to be needed. Confirmed ACR criteria provided the best predictive accuracy. Given limited resources, identifying subjects based on the SLE portion of the CSQ questionnaire could be most efficient for follow-up.

Table 1. Predictive Accuracy of Baseline Characteristics for Transitioning to SLE.

« Back to 2017 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/identification-of-key-screening-characteristics-for-systemic-lupus-erythematosus-natural-history/