Abstract
Purpose: :
Sjogren syndrome is an autoimmune disorder characterized by lacrimal gland destruction that also affects numerous non-ocular tissues. Lymphocytic infiltrates of the lacrimal and salivary glands, the hallmark of Sjogren syndrome, lead to the prominent clinical features of dry eye and dry mouth. It is well recognized that dry eye disease (DED) manifestations are often more severe and associated with a higher incidence of corneal complications in Sjogren (SS) patients than in non-Sjogren (NS) patient. A post hoc analysis was performed to evaluate the outcomes of SS and NS patients with moderate to severe DED participating in a randomized clinical trial.
Methods: :
The Siccanove study was a 6 month phase III, multicenter, randomized, controlled, double-masked trial of Cyclokat (0.1% cyclosporine cationic emulsion) administered once daily versus its cationic emulsion vehicle in 492 patients with moderate to severe DED (grade 2-4 corneal fluorescein staining, CFS, on the modified Oxford scale). Mean change in corneal fluorescein staining (CFS) and the mean change in DED symptoms measured using the OSDI from baseline were assessed at month 6.
Results: :
Of the 379 analyzed patients 123 (37%) had SS and 237 (63%) were had NS. The improvement in DED symptoms in the Cyclokat group compared to vehicle was greater in both SS and NS patients and was similar across all levels DED severity at baseline as defined by CFS (Grades 2-4: -15.8 vs -13.6 SS and -15.8 vs -10.9 NS; Grades 3-4: -16.3 vs -12.0 SS and -15.5 vs -9.9 NS; Grade 4: -15.2 vs -11.7 SS and -20.2 vs -8.1 NS). While both SS and NS patients treated with Cyclokat showed greater improvements in CFS over the vehicle at all levels of severity (Grade 2-4: -1.0 vs -0.7 SS and -1.2 vs -0.8 NS; Grades 3-4: -1.0 vs -0.8 SS and -1.4 vs -0.9 NS; Grade 4: -1.5 vs -0.6 SS and -1.8 vs -0.6 NS), at all levels of severity NS patients treated with Cyclokat showed greater improvement than SS patients (CFS improvement Grade 2-4: -1.0 SS vs -1.2 NS; Grade 3-4: -1.0 SS vs -1.4 NS Grade 4 -1.5 SS vs -1.8 NS).
Conclusions: :
Treatment with Cyclokat showed the greatest benefit in patients with most severe keratitis in both SS and NS patients. The response to DED symptoms evident in both treatment groups seemed not to differ between SS and NS patients and may be a positive benefit of the cationic emulsion formulation. The greater improvement in keratitis in NS over SS patients supports the clinical notion that DED in SS patients is more difficult to treat and could argue for longer term topical anti-inflammatory treatment in DED patients with this underlying systemic disease.
Clinical Trial: :
http://www.clinicaltrials.gov NCT00814515
Keywords: cornea: tears/tear film/dry eye • clinical (human) or epidemiologic studies: treatment/prevention assessment/controlled clinical trials • cyclosporine