Treatment of Primary Sjögren's Syndrome Reviewed

Laurie Barclay, MD

July 28, 2010

July 28, 2010 — There is a very low level of evidence for the majority of drugs currently used in primary Sjögren's syndrome, according to the results of a systematic review reported in the July 28 issue of the Journal of the American Medical Association.

"A variety of topical and systemic drugs are available to treat primary Sjögren syndrome, although no evidence-based therapeutic guidelines are currently available," write Manuel Ramos-Casals, MD, PhD, from Sjögren Syndrome Research Group (AGAUR), Hospital Clínic in Barcelona, Spain, and colleagues. "The purpose of this systematic review was to analyze and summarize the evidence on drug therapies (topical and systemic) for the main clinical manifestations of primary Sjögren syndrome (sicca symptoms and extraglandular involvement) in adults."

The reviewers searched MEDLINE and EMBASE for articles on drug treatment of primary Sjögren's syndrome published between January 1, 1986, and April 30, 2010. There were 37 studies identified meeting inclusion criteria of randomized controlled trials of topical and systemic drugs tested in adult patients with primary Sjögren's syndrome.

In a placebo-controlled trial, patients treated with topical ocular 0.05% cyclosporine had significant improvement in the Schirmer and corneal staining scores, blurred vision, and artificial tear use. In 3 placebo-controlled trials, pilocarpine was associated with improvements in dry mouth (61% - 70% vs 24% - 31% for placebo) and in dry eye (42% - 53% vs 26%).

Cevimeline was associated with improved dry mouth in 2 placebo-controlled trials (66% - 76% vs 35% - 37% in the placebo group), as well as with improved dry eye (39% - 72% vs 24% - 30%). Oral prednisone or hydroxychloroquine did not significantly improve sicca outcomes in small trials enrolling fewer than 20 patients. Benefits were limited for the immunosuppressive drugs azathioprine and cyclosporine evaluated in small trials.

Oral interferon alfa-2a was associated with limited benefits in a large trial. The primary outcome (a composite visual analog scale measuring joint pain, fatigue, and dryness) was not reached in 2 placebo-controlled trials of infliximab and etanercept or in 2 small trials of rituximab in fewer than 30 patients. However, some secondary endpoints showed significant improvements from baseline.

"In primary Sjögren syndrome, evidence from controlled trials suggests benefits for pilocarpine and cevimeline for sicca features and topical cyclosporine for moderate or severe dry eye," the review authors write. "Anti–tumor necrosis factor agents have not shown clinical efficacy, and larger controlled trials are needed to establish the efficacy of rituximab."

Limitations of this study include those inherent in the included studies.

"In the last 3 decades, therapeutic approaches in primary Sjögren syndrome have been based on the use of substitute agents for sicca features and glucocorticoids and immunosuppressive agents for extraglandular involvement," the review authors conclude. "The emergence of new immunosuppressive agents and biologic therapies has increased the therapeutic armamentarium available in the most severe situations, but their use is limited by the lack of specific licensing. This systematic review highlights the limited evidence available for the drugs most frequently used in primary Sjögren syndrome and the difficulties of offering solid therapeutic recommendations."

La Marató de TV3 and Fondo de Investigaciones Sanitarias supported this study. The review authors have disclosed no relevant financial relationships.

JAMA. 2010;304:452-460.


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