Etanercept in Sjögren's syndrome: A twelve‐week randomized, double‐blind, placebo‐controlled pilot clinical trial

Abstract

Objective. To assess the safety and potential efficacy of etanercept in the treatment of Sjögren's syndrome (SS).Methods. This pilot study was a 12-week randomized, double-blind, placebo-controlled trial of etanercept, with 14 subjects in each group. Patients received 25 mg of etanercept or placebo (vehicle) by twice-weekly subcutaneous injection. Patients met the AmericanEuropean Consensus Group criteria for SS. The primary outcome required at least 20% improvement from baseline values for at least 2 of the following 3 domains: subjective or objective measures of dry mouth, subjective or objective measures of dry eyes, and IgG level or erythrocyte sedimentation rate (ESR).Results. Of the 14 patients taking etanercept, 11 had primary SS and 3 had SS secondary to rheumatoid arthritis. Baseline measures did not differ between the 2 groups. Three etanercept-treated patients and 1 placebo-treated patient did not complete the trial. Five etanercept-treated patients and 3 placebo-treated patients showed improvement from baseline in the primary outcome variable at 12 weeks, but the difference was not statistically significant. There were no significant differences between the groups for changes in subjective measures of oral or ocular symptoms (by visual analog scale), the IgG level, Schirmer I test result, van Bijsterveld score, or salivary flow. At 12 weeks, the ESR had decreased in the etanercept group compared with baseline (P ‫؍‬ 0.004); however, the mean reduction was only 18.6%.Conclusion. We found no evidence to suggest that treatment with etanercept at a dosage of 25 mg twice weekly for 12 weeks was clinically efficacious in SS. A larger trial will be necessary to definitively address the efficacy of etanercept in the treatment of SS.

Augmented interferon‐α pathway activation in patients with Sjögren's syndrome treated with etanercept

“…In contrast to the success of this therapeutic approach in those diseases, and in spite of the documented presence of TNF␣ in labial salivary gland biopsy samples from SS patients (15), a pilot study of etanercept and 2 randomized placebo-controlled trials failed to show a significant effect of anti-TNF agents on clinical disease manifestations (18)(19)(20).…”

Effectiveness of abatacept for patients with Sjögren’s syndrome associated with rheumatoid arthritis. An open label, multicenter, one-year, prospective study: ROSE (Rheumatoid Arthritis with Orencia Trial toward Sjögren’s syndrome Endocrinopathy) trial

“…With regard to other biologics, TNF inhibitors (infliximab and etanercept) are reported to have no significant effects on glandular or extra-glandular manifestations of SS [13,14]. Although B cell activating factor (BAFF) is a promising biologic for SS, belimumab, a monoclonal anti-BAFF antibody, did not improve salivary flow or lacrimation, although it significantly decreased a composite of disease activity measures, including the European League Against Rheumatism (EULAR) Sjögren's Syndrome Disease Activity Index (ESSDAI) and EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) [15].…”

Diagnosis and treatment of primary Sjogren’s syndrome: an update

“…However, the study was halted due to the potential of this biological agent to cause progressive multifocal leukoencephalopathy [26]. Anti-TNF alpha agents including infliximab [27] and etanercept [28] both failed to demonstrate efficacy in primary SS. Interferon-targeted therapy has been studied in primary SS as well.…”