2016 American College of Rheumatology/European League Against Rheumatism Classification Criteria for Primary Sjögren's Syndrome: A Consensus and Data-Driven Methodology Involving Three International Patient Cohorts

Abstract

Objective: To develop and validate an international set of classification criteria for primary Sjögren's syndrome (SS) using guidelines from the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR). These criteria were developed for use in individuals with signs and/or symptoms suggestive of SS.

Methods: We assigned preliminary importance weights to a consensus list of candidate criteria items, using multi-criteria decision analysis. We tested and adapted the resulting draft criteria using existing cohort data on primary SS cases and non-SS controls, with case/non-case status derived from expert clinical judgment. We then validated the performance of the classification criteria in a separate cohort of patients.

Results: The final classification criteria are based on the weighted sum of 5 items: anti-SSA/Ro antibody positivity and focal lymphocytic sialadenitis with a focus score of ≥1 foci/4 mm2 , each scoring 3; an abnormal ocular staining score of ≥5 (or van Bijsterveld score of ≥4), a Schirmer's test result of ≤5 mm/5 minutes, and an unstimulated salivary flow rate of ≤0.1 ml/minute, each scoring 1. Individuals with signs and/or symptoms suggestive of SS who have a total score of ≥4 for the above items meet the criteria for primary SS. Sensitivity and specificity against clinician-expert-derived case/non-case status in the final validation cohort were high, i.e., 96% (95% confidence interval [95% CI] 92-98%) and 95% (95% CI 92-97%), respectively.

Conclusion: Using methodology consistent with other recent ACR/EULAR-approved classification criteria, we developed a single set of data-driven consensus classification criteria for primary SS, which performed well in validation analyses and are well-suited as criteria for enrollment in clinical trials.

© 2016 The Authors. Arthritis & Rheumatology published by Wiley Periodicals, Inc. on behalf of the American College of Rheumatology.

Figures

Figure 1

Overview of methodology used for the definitive set of Sjögren’s syndrome classification criteria based on both data and expert clinical judgment. Item generation was derived from both the 2002 American-European Consensus Group (AECG) criteria and the 2012 American College of Rheumatology (ACR) criteria 1 UWS: Unstimulated whole saliva flow rate; VB: van Bijsterveld; OSS: Ocular staining score; FS: focus score computed from labial salivary gland biopsy in the presence of focal lymphocytic sialadenitis; RF: rheumatoid factor; ANA: antinuclear antibody titer 2 International SS Criteria Working Group meetings held during the 2013 International Symposium on Sjögren’s syndrome (ISSS) in Kyoto, Japan, and the 2013 American College of Rheumatology (ACR) annual meeting in San Diego, California 3 MCDA: multi-criteria decision analysis survey performed using 1000Minds software 4 Disease case and non-case status were derived from expert clinical judgment based on clinical vignettes for both development and validation cohorts

Figure 2

Distributions of clinician expert assigned weights for seven items included in the MCDA survey. Curves are kernel-smoothed probability density estimates and the vertical scale can be interpreted similarly to relative frequency histograms.

Figure 3

variable importance for random forest classification of clinician expert case/non-case designations in development data vignettes. A: based on all vignette variables; B: restricted to binary indicators consistent with the MCDA survey items.