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Limited evidence shows minimal effectiveness of drug therapy for primary Sjögren Syndrome

Dena Fischer DDS, MSD, MS .


Systematic Review Conclusion

Evidence suggests benefits of oral sialagogues and topical ocular cyclosporine for management of the subjective dry mouth and eye symptoms of primary Sjögren syndrome.

Critical Summary Assessment

Although the quality of this systematic review is acceptable, the evidence to support clear therapeutic recommendations is very limited.

Evidence Quality Rating

Limited Evidence

Structured Abstract

Clinical Questions:

In adult patients with primary Sjogren syndrome, do currently utilized drug therapies compared to standard drug or untreated controls have enough evidence to support its use to relieve sicca syndrome (dry mouth and dry eyes) and extragladular involvement?

Review Methods:

The review authors conducted an electronic search of two databases from January 1986 through April 2010 for articles published in English. They also searched reference lists and contacted study authors when necessary. The authors included only randomized controlled trials (RCTs) or prospective cohort studies on adult human subjects who were treated for primary SS using drug therapy. Comparison groups were either untreated controls or standard of care drug. Further inclusion criteria required that studies contain clear information about the effect of the drug on the clinical outcomes of xeropthalmia (dry eyes), xerostomia (dry mouth), general symptoms, and/or extraglandular involvement. Three independent reviewers selected studies, extracted data, and assessed the methodological quality of the studies using the Cochrane Collaboration tool for assessing risk of bias. Any disagreement was resolved by discussion.

Main Results:

The review authors found 37 controlled trials (5 with a crossover, washout design) and 19 prospective cohort studies that met all inclusion/exclusion criteria. Sixteen trials included only primary SS patients, while the other studies included patients with primary SS or associated symptoms. The duration of follow-up ranged from 4 weeks to 1 year. Therapies evaluated included eyedrops (n=12 studies), oral sialogogues (n=9), immunomodulatory or immunosuppressive drugs (n=14), biologic therapies (n=9) and miscellaneous drugs (n=12). Two of three RCTs comparing topical cyclosporine eyedrops to placebo found a benefit using objective criteria for dry eyes. Because the comparison group was placebo rather than another drug therapy, the clinical significance of these findings remains questionable. Five of seven placebo-controlled trials of oral sialogogues (pilocarpine and cevimeline) reported a significant improvement in subjective dry mouth and dry eye symptoms. Use of sialagogues resulted in a 61-76% improvement in dry mouth compared to 24-37% with placebo, and a 39-72% decrease in dry eye symptoms while use of placebo resulted in 24-30% reduction. No direct comparison between oral sialogogue drugs was found. Studies of other therapeutics and for the outcomes of general symptoms and extraglandular involvement were inconclusive.


Evidence suggests some benefit for pilocarpine and cevimeline for sicca features and topical cyclosporine for moderate or severe dry eyes in primary SS. No conclusive evidence is available for the other therapeutics. The quality of evidence is limited.

Source of Funding:

The study was supported by grants from La Marató de TV3 and Fondo de Investigaciones Sanitarias.


Importance and Context:

SS is a systemic autoimmune disease that affects 0.5 to 3 million persons in the United States (Helmick, 2008). Primary SS presents with sicca symptomatology of mucosal surfaces, mainly dry mouth and dry eyes, in a previous healthy person. There are no evidence-based therapeutic guidelines for management of primary SS. Consequently, therapeutic decisions are mostly based on decreasing symptoms using topical and systemic medications. A few new therapeutic approaches are now available. Helmick CG, Felson DT, Lawrence RC, et al; National Arthritis Data Workgroup. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States: part I. Arthritis Rheum. 2008;58 (1):15-25.

Strengths and Weaknesses of the Systematic Review:

This SR followed generally accepted methodological guidelines, though some limitations were identified. The review authors determined inclusion and exclusion criteria a priori and assessed included studies in triplicate for heterogeneity of study design and risk of bias. However, a complete analysis of all included studies was not provided. The study characteristics of only 14 of 56 studies were presented in Tables 1, 2 and 3. Further, limited search terms were utilized, only English articles were included in the SR, and only two electronic databases were searched. Finally, the authors did not state why they did not combine results through a meta-analysis.

Strengths and Weaknesses of the Evidence:

There were a large number of studies available for review, some with large populations of subjects. However, variations existed amongst studies in the definition of primary SS, and there was heterogeneity in the study outcomes due to lack of objective, standardized criteria. In addition, studies were heterogeneous with respect to study quality, length of follow-up, types of control groups, and outcome definitions and reporting, all of which could introduce bias into the results. It is unclear if confounding factors that may have affected the outcomes were addressed. Both patient-oriented and disease outcomes were reported in the literature, and adverse effects of drugs were reported. The level of the available evidence was limited. Only a few studies (less than 10%) compared drugs (rather than comparison to placebo) in clinical scenarios.

Implications for Dental Practice:

No clear cut therapeutic recommendations could be made. There is limited evidence available for the therapies most frequently used to manage primary SS. Although some studies reported statistically significant improvements in SS symptoms with the use of a therapeutic agent, the comparison was against placebo. It has to be noted that comparison against placebo has to be considered with caution, as most drugs will show effect when compared to no treatment. Additionally the systematic review itself did not conduct any statistical analysis. As expected, the most effective drugs attempt to decrease the symptoms associated with this condition. Standardized diagnosis and outcome criteria are needed to better assess therapies for SS. This would provide a better indication of the clinical significance of the therapies.

Critical Summary Publication Date:


These summaries are not intended to, and do not, express, imply, or summarize standards of care, but rather provide a concise reference for dentists to aid in understanding and applying evidence from the referenced systematic review in making clinically sound decisions as guided by their clinical judgment and by patient needs. American Dental Association © 2018