Researchers are continuing to investigate Sjogren's syndrome in hopes of gaining a deeper understanding about the pathophysiology of the disorder and using this information to develop novel approaches for improved treatments. Some of the current areas of research interest in Sjogren's syndrome include:

• Treatment of Sjogren's syndrome is a topic of active investigation. Researchers are investigating treatments not only for the dry eye and dry mouth symptoms but also to modify the progression of the disease. New approaches include interference with inflammation processes and chemical receptors as well as strategies to preserve and restore functional exocrine tissue. To read more about emerging treatment strategies and potential therapeutic targets in primary Sjogren's syndrome, please click on the following link: http://www.ncbi.nlm.nih.gov/pubmed/19906008
• To assess the effect of rituximab therapy on parotid tissue in Sjogren's disease, five patients underwent a parotid biopsy before starting a regimen of rituximab and subsequently underwent an addition parotid biopsy after 12 weeks of rituximab infusions. Results showed that following treatment:
  • four of the five patients showed an increased salivary flow rate and a normalization of salivary sodium concentration
  • lymphocytic infiltrate of the parotid gland was reduced in all five patients
  • in three patients, the amount and extent of a particular type of lesion was reduced, and in two patients, it was completely absent
  • the proliferation of cluster-like tissue that forms in response to inflammation was reduced in all patients

The authors concluded that the histopathologic evidence of reduced glandular inflammation seen in this small subset of Sjogren's patients may indicate the potential for glandular restoration with rituximab. To read more about this study, please click on the following link: http://www.ncbi.nlm.nih.gov/pubmed/19877054

Therapies for Dry Mouth under Investigation for Sjogren's Syndrome

• Evaluation of a mouth rinse solution containing casein derivative calcium phosphate (CD-CP) to help prevent tooth decay in patients with dry mouth.
• Evaluation of trithio-p-methoxyphenylpropene (Sialor) for stimulating salivary secretion in patients with dry mouth.
• Transplantation of submandibular salivary glands is in early stages of research as a potential treatment for xerostomia.
• A clinical trial investigating the drug mizoribine for treatment of sicca syndrome yielded promising results in patients' assessment of improvement. To read more about this treatment, please click on the following link: http://www.ncbi.nlm.nih.gov/pubmed/18506160
• There is an ongoing effort to produce saliva substitutes based on new thickening agents such as linseed polysaccharide or xanthan gum polysaccharide to achieve longer adherence on mucosal surfaces.
• Researchers are studying a treatment involving irrigation of the parotid gland with prednisolone.
• Efforts are underway to reformulate pilocarpine as a slow-release medication that will deliver medication at a slow, steady rate over a longer period of time than the present form.
• Here is a link to an interesting study investigating the effect of homeopathic medicine on salivary flow rates: http://www.ncbi.nlm.nih.gov/pubmed/16060203

Dry Eye Therapies under Investigation for Sjogren's Syndrome

• Researchers at the Massachusetts Eye and Ear Infirmary in Boston investigated the efficacy of multiple daily dosing of topical cyclosporine 0.05% for patients with severe dry eye disease who did not respond to the usual twice-a-day regimen. Twenty-two patients were given topical cyclosporine 0.05% either three or four times a day for a two-month course of treatment. Overall dry eye symptoms improved in 15 patients (68%) and global physician assessment of dry eye status improved in 16 patients (72%). Three patients (13%) reported new symptoms of burning or irritation. The authors conclude that patients with severe dry eye symptoms that do not respond to a twice-daily regimen may require more frequent dosing of topical cyclosporine. To read more about this study, please click on the following link: http://www.ncbi.nlm.nih.gov/pubmed/19770713
• Cevimeline (Evoxac), a drug that has already been approved by the U.S. Food and Drug Administration (FDA) for the treatment of dry mouth, is also being evaluated as a potentially safe and effective treatment for dry eye.
• Topical therapy with cyclosporin A is being evaluated for the treatment of dry eye.
• Novel topical agents that are designed to enhance the transport of water across the conjunctiva by stimulating specific receptors in the eye known as purinogenic ocular surface receptors are being developed for the treatment of dry eye.
• Eye-drops formulated with hyaluronate show promise for the treatment of severe dry eye in Sjogren's patients.
• Novel secretogogues that target secretion of mucins which form the inner layer of the tear film and are responsible for lubrication and protection including:
  • INS365 (diquafosol tetrasodium) - improved test scores of Schirmer test and corneal/conjunctival staining
  • 15S-HETE
  • ecabet sodium - an anti-ulcer agent that has shown promise for treatment of dry eye
  • gefarnate - used in the treatment of gastric ulcers and has shown potential for treatment of dry eye
• Gene transfer of therapeutic agents (such as immunomodifying agents) into the affected gland has successfully been studied in animals. Researchers are investigating the potential of carrying out this model for treatment in humans.

Systemic Treatments under Investigation for Sjogren's Syndrome

• Results from a clinical trial that took place in Leeds, Great Britain showed a reduction of fatigue levels with rituximab infusions. To read more about this just-published study, please click on the following link: http://www.ncbi.nlm.nih.gov/pubmed/18276741
• Results of a clinical trial investigating the treatment of autoimmune-related interstitial lung disease with mycophenolate mofetil (MMF) instead of cyclophosphamide (CYC) were published in 2009 in the American Journal of Medical Science. Cyclophosphamide is associated with significant toxicity and poor outcome. Ten patients received MMF while five patients received CYC infusion. Results were encouraging regarding MMF-treated patients who showed improvement in alveolitis (diffuse interstitial lung disease), symptoms related to coughing, dyspnea, and chest discomfort, and perceived quality of life and activity levels. In addition, average doses of prednisone were reduced significantly without worsening of the patient's condition. To read more about this study, please click on the following link: http://www.ncbi.nlm.nih.gov/pubmed/19295413
• Research regarding development of biologic agents which target B-cells and T-cells in Sjogren's syndrome is very robust. B-cell targeting medications under investigation include:
  • rituximab
  • ocrelizumab
  • epratuzumab
  • belimumab
• T-cell targeted therapies include:
  • efalizumab (Raptiva)
  • alefacept (Amevive)
  • abatacept (Orencia)

NOTE: Efalizumab (Raptiva) is a medication that is used for the treatment of a condition called psoriasis - a chronic skin disease characterized by dry red patches covered with scales. In April 2009, this drug was withdrawn from the U.S. market due to the potential risk of patients developing progressive multifocal leukoencephalopathy - a usually fatal condition that is characterized by progressive brain damage due to inflammation of the white matter of the brain. Efalizumab (Raptiva) is no longer available in the U.S. as of June 8, 2009.