Sjögren Syndrome: An A-to-Z Update

Robert I. Fox, MD, PhD; Carla M. Fox, RN


December 03, 2013

In This Article

Treatment Options

Abatacept reduced disease activity in early primary Sjögren syndrome in a phase 2 open-label study.[22] Patients with disease duration less than 5 years and who were not previously treated with disease-modifying antirheumatic drugs were enrolled. Abatacept was well-tolerated and showed significant reductions in ESSDAI score. However, the clinical trials of abatacept in SLE were terminated due to safety concerns.[23]

Seror and colleagues[24] reported an improved pattern of lymphocyte infiltrates on serial lip biopsy in 2 small European trials of belimumab (the BELISS study). Among 15 treated patients, the ESSDAI and BAFF levels showed significant improvement. As these trials were not placebo controlled, it is difficult to establish clinical efficacy. Levels of endothelial growth factor are lower in belimumab-treated patients.[25]

However, the most interesting part of the discussion is that patients showed relatively less subjective improvement in their ocular and oral symptoms than would be expected from their overall improvement. This suggests that we may improve peripheral extraglandular manifestations, but we are still missing a key element of Sjögren syndrome that regulates pain, myalgia, and fatigue.

A review of biologics in the European registry for Sjögren syndrome during the past 2 years indicated that the most frequently used agent was rituximab.[26] Jousse-Joulin and colleagues[27] reported an improvement in ultrasound of the salivary glands in the TEAR and TRACTISS studies conducted in the United Kingdom and France. (Both small studies used a placebo control.) However, corresponding changes in lip biopsy were not observed.

Discussion of this interesting paper indicated that most rheumatologists were using rituximab for specific flares such as vasculitis, including mixed cryoglobulinemia, hematopoietic changes (eg, hemolytic anemia or thrombocytopenia), or parotid gland swelling on an as-needed basis rather than on a continuous basis.

Promising agents in preclinical development for Sjögren syndrome and SLE include the following:

Anti-CD22 (epratuzumab);


Atacicept (anti-TACI);

Anti-IL6 (tocilizumab);



Anti-interferon type 1; and

Anti-C5a (eculizumab).

Traditional drugs, including methotrexate (for arthritis), azathioprine (for nephritis), and mycophenolic acid to help taper the steroid dose, remain our standard of care.

Other trials currently in progress are studying low-dose cyclosporine with the hopes of finding a dose that is efficacious, but not renally toxic. Gottenberg and colleagues[28] reported that the rate of serious infections remains stable in patients with multiple retreatments based on the rituximab (AIR) registry.

Although more than 60% of patients sustained a serious infection, they continued to receive rituximab when their systemic manifestations required treatment.

About 5% of patients had serious adverse events after the first cycle and similar percentages after subsequent trials including a cohort with 5 cycles.

The treatment of extraglandular features such as vasculitis, rash, or parotid swelling was effective. The treatment of chronic benign symptoms of oral/ocular pain was disappointing.

In summary, there is a great deal of interest on the part of the pharmaceutical industry in Sjögren syndrome, and that is encouraging. However, the current results have limited benefit on the "benign" symptoms (fatigue, myalgia, cognitive) that patients most consider limitations to their quality of life. Symptomatic therapies remain largely unchanged over the past decade.


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