Sjogren’s syndrome – its time has come

Sjogren’s syndrome is a systemic autoimmune disease.  The infiltration of exocrine tissues, such as the salivary and lacrimal glands, has been termed autoimmune exocrinopathy.  It has also been called epitheliitis or epithelitis, because the infiltration does not only affect exocrine glands, but involves other exocrine tissues.  The disease manifestations include involvement of the joints, respiratory system, urinary tract, neurological system, and skin.  Sjogren’s syndrome is associated with the highest frequency of lymphoma among the autoimmune rheumatic diseases.

In the past decade, research has advanced our knowledge of the epidemiology, immunological mechanisms, and outcomes in Sjogren’s syndrome.  Efforts to develop new outcome measures for clinical trials were hampered by having few or marginally efficacious treatments for the systemic aspects of the disease.

New advances in B-cell based treatments for rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) have spilled over into Sjogren’s syndrome.  Rituximab is under active investigation for Sjogren’s syndrome and results thus far are not discouraging.  A dividend of such studies has been the opportunity to evaluate outcome measures for the disease.  In addition, the treatment of Sjogren’s syndrome with the anti-BLyS or anti-BAFF agent, belimumab is also under investigation. Interestingly, BLyS/BAFF has higher expression in Sjogren’s syndrome than in other autoimmune rheumatic diseases, including SLE. Benlysta (belimumab) was recently approved by the FDA for treatment of SLE.  At the time, this was the first time that a drug was specifically approved for SLE in over 50 years.  While Salagen (pilocarpine) and Evoxac (cevimeline) were approved for the symptoms of oral or ocular dryness occurring Sjogren’s syndrome, they are secretogogues that do not address the immunological component of the disease, unlike belimumab and rituximab.
In SLE, type 1 interferons, such as interferon alpha have increased expression, and the same is true for Sjogren’s syndrome.  This is therefore another target of interest and anti-interferon alpha biologics could have potential in the treatment of Sjogren’s syndrome.
Currenlty, there is no drug that has been specifically approved for treatment of the autoimmune component of Sjogren’s syndrome.  Yet new advances in the understanding of the mechanisms of Sjogren’s syndrome, the availability of drugs that appear promising, and responders in clinical trials of immunological agents that are allowing for the validation of outcome measures indicate that the time has come for Sjogren’s syndrome