Background/Purpose: , Primary Sjögren’s Syndrome (pSjS) is a systemic autoimmune inflammatory disease that primarily affects the lacrimal and salivary glands and is associated with B cell hyper-reactivity and elevated serum concentrations of Blys. Belimumab is approved for the treatment of Systemic Lupus Erythematosus, where B cell mediated inflammation is commonly seen.  In this retrospective study, we examined the off-label use of belimumab in a small cohort of pSjS with systemic manifestations.  We analyzed clinical endpoints based on questionnaires and patient reported outcomes (PROs) as well as multiple serum biomarkers, individually measured as part of a multi-biomarker disease activity assay (MBDA), used predominantly in RA. Vectra DA is a cumulative score based on the serum concentrations of 12 serum proteins (biomarkers); although the score has been validated for use in RA, several components of the test have been implicated in the pathogenesis of SjS.

Methods: , A retrospective chart review study was conducted at a teaching hospital and nine patients diagnosed with pSjS were identified, as defined by the American-European group consensus criteria. The patient’s age ranged from 26 to 73 (mean: 51).  All patients studied (1 male, 8 females) had confirmatory minor salivary gland biopsy (focal score>1), 3/9 (33%) were African American and 6/9 (67%) Hispanic.  Of the 9 patients studied, 4 were also treated with monthly belimumab infusions (10 mg/kg), as an add-on treatment to address predominantly extra-glandular manifestation, such as arthritis and fatigue, for approximately 60 weeks.  Vectra was done for all patients and clinical improvement was assessed by RAPID-3 and FACIT-F scores during the course of the treatment.  Individual biomarker concentrations were compared in the 2 groups using the Wilcoxon Exact test.

Results:  The results for EGF biomarker suggest that there is a statistically significant difference between the underlying distributions of the EGF scores of control group and the EGF scores of Belimumab group (p = 0.03, r=-0.71).  The patients on Belimumab had numerically lower serum concentrations of VCAM-1, VEGF-a, IL-6, MMP-3, YKL-40, Leptin, Resistin, SSA, and CRP biomarkers and higher concentrations of the TNF-RI and MMP-1 biomarkers compared to the control group, although the difference did not reach statistical significance.  Vectra-DA scores for the belimumab group (mean: 38) and the control group (mean: 31.5) were similar in both groups and were not affected by treatment.  Clinical endpoints, such as the RAPID-3 and FACIT scores, did not show a difference between the two groups.

Conclusion:   In our pSjS cohort, treatment with Belimumab was associated with significantly lower EGF concentrations, albeit no apparent extra-glandular clinical improvement. Controlled studies and development of more specific disease activity measures are needed.