Elsevier

Journal of Autoimmunity

Volume 51, June 2014, Pages 51-56
Journal of Autoimmunity

Review
Outcome measures for primary Sjögren's syndrome: A comprehensive review

https://doi.org/10.1016/j.jaut.2013.12.010Get rights and content

Highlights

  • ESSDAI and ESSPRI have been developed for evaluation primary Sjögren's patients.

  • Both indexes have been proven to be valid, reliable, sensitive to change.

  • ESSDAI or ESSPRI are complementary and should be used together.

  • These indexes may help to improve conduction of clinical trial in primary Sjögren's syndrome.

  • ESSDAI or ESSPRI should be used as outcome measure in clinical trials.

Abstract

Lymphocytic infiltration of different exocrine and non-exocrine epithelia is the pathological hallmark of primary Sjögren's syndrome, whereas involvement of salivary and lachrymal glands with the clinical counterpart of dry eye and dry mouth are the predominant features of the disease, together with fatigue and musculoskeletal pain. In addition, systemic manifestations, like arthritis, skin vasculitis, peripheral neuropathy, glomerulonephritis, may also be present in a consistent number of patients. As result, clinical features in SS can be divided into two facets: the benign subjective but disabling manifestations such as dryness, pain and fatigue, and the systemic manifestations. In the past decades, great efforts have been made to develop valid tools for the assessment of these both facets. Disease specific questionnaires such as Profile of Fatigue and Discomfort (PROFAD) and Sicca Symptom Inventory (SSI) have been proposed for evaluation of patients' symptoms, whereas different composite indexes have been suggested for the assessment of systemic disease activity. After that, an international project supported by EULAR, emerged to develop consensus disease activity indexes: the EULAR Sjögren's Syndrome Patients Reported Index (ESSPRI), and the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI), a systemic activity index to assess systemic manifestations. Both EULAR indexes have been developed in an international collaboration to be consensual. Both indices have now been validated in a large independent international cohort. They both have been shown to be feasible, valid and reliable instruments. Also, we have found that these two scores did not correlate, suggesting that these two indexes assess two different disease components that poorly overlap, but were complementary. The sensitivity to change of both scores has been assessed, they are both able to detect change, however, ESSDAI score, like other systemic score, is more sensitive to change than ESSPRI and other patient scores. Current work is ongoing to define disease activity levels and clinically important changes for defining significant clinical improvement with the systemic score ESSDAI, and ESSPRI. We hope that this increased knowledge on the way to assess patients with primary SS, along with the emergence of new targeted therapy, will put a great input in the improvement of conduction of clinical trials in pSS.

Section snippets

Assessment of systemic disease activity: the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI)

For evaluation of systemic activity, the SSDAI was the first activity index proposed for SS. It offered the advantage of great simplicity, but the major disadvantage is of a lack of exhaustiveness, which results in an important floor effect with more than half of the patients having a score of 0 or 1 in a real life cohort of primary SS patients [26]. By contrast, the SCAI is much more exhaustive, but is so complex to rate that it is very difficult to use in clinical practice. Compared to

EULAR validation study

Both ESSDAI and ESSPRI have been recently validated in a prospective international cohort that included 395 patients in 15 countries [29]. The aim of this study was to evaluate psychometric properties (construct validity, responsiveness and reliability) and compare them to that of previous scores: SSDAI and SCAI for ESSDAI and SSI and PROFAD for ESSPRI. Like all scores, EULAR scores had excellent reliability. However, they have been found to have better construct validity (i.e. higher

Future steps: conducting clinical trials

The objective is now for these indexes to be used as outcome criteria in randomized controlled trial, in order to be able to demonstrate, if any, efficacy of treatments. Effectively, the treatment of pSS remains a challenge, since most of randomized controlled trials, even the most recent ones, failed to demonstrate efficacy of the evaluated treatment. Hydroxychloroquine which is the most frequently proposed treatment, is used based on observational studies [49] and one cross-over study that

Conclusion

We have now two validated indexes to completely assess disease features of primary SS patients. These tools are complementary and should be used together in addition to objectives measures of dryness and biological markers of activity. Depending on the component of disease that is the target of the treatment, ESSDAI or ESSPRI should be outcome measure of clinical trials. Work is currently in progress to better define disease activity levels and response criteria using these indexes. This

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    On behalf of the EULAR Sjögren's Task Force.

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