Tuesday, December 7, 2010

Rituximab for Sjogren's Syndrome

Rituximab is a man made antibody most frequently used in the treatment of autoimmune Rheumatoid Arthritis and B cell non-Hodgkins Lymphoma - a type of cancer. Rituximab is a type of chemotherapy agent. In 2008 it was the world's best selling cancer drug.

A study was published in the journal Arthritis Rheum Jan, 2010 that discussed its use in patients with primary Sjogren's Syndrome - an autoimmune disease that primarily affects the moisture producing (exocrine) glands.

In any autoimmune disease, the body mistakenly begins to attack its own cells (self). The immune system is multi-faceted and works much like an army. Autoimmunity is largely a mystery, but what is known is the system somehow (there can be multiple mechanisms) 'forgets' which cells are foreign and which cells are self. The body targets self, and healthy cells are destroyed by friendly fire.

Rituximab is an injectible chimeric antibody. (A chimera is a mythical creature with body parts from different animals) In this case, Rituximab is part human and part mouse. Because it is prepared using the cells/proteins of living creatures it is called a biologic. Because it depletes the immune system it is also called a DMARD - Disease Modifying Anti-Rheumatic Drug.

Rituximab is used mixed with other fluids and given via IV once weekly. Each infusion may take 3-4 or more hours. It works as an autoimmune treatment by depleting the number of B cells - one of the many types of specialized cells in the immune system that play a part in inflammation. Normally, inflammation is a necessary and normal immune response. In autoimmune primary Sjogren's Syndrome, the inflammatory response is out of control.

Rituximab is not a first line drug. It is used only when other biologic medications have failed. Rituximab is an antibody that is specific for a molecule called CD20 that is normally present on the surface of B cells. The cells are targeted and lysed (destruction via explosion) by the Rituximab antibodies.

There can be significant side effects, especially during or shortly after the first or second doses. One of those side effects is called serum sickness. In serum sickness, the body reacts negatively to the introduction of a foreign protein (the Rituximab) into the system. Reactions can range from mild to life threatening. It is interesting to note that serum sickness was noted in 3 of 8 patients in an earlier study in which low or no corticosteroids were used, but in only one diabetic patient in the second study of 30 patients in which higher doses of steroids were used.

It is unknown if the use of steroids in the second study helped to increase the positive outcome for Rituximab and placebo patients (slight improvement at 5 weeks) in that study, but it seems suggestive that it may have helped to prevent serum sickness in the Rituximab patients.

In the respective studies, improvement was seen in these areas: secretion of saliva as well as inflammatory activity within the saliva, improved lab values (ESR, IgG, FACS analysis on B and T cells), fatigue, parotid (salivary gland) biopsies, and there were fewer extraglandular symptoms (joint pain, kidney involvement, etc). There was no increase seen in tear production. The most significant point in time at which improvement was noticed in the second study was between 12 - 36 weeks of treatment.

Because Sjogren's patients are at increased risk for B cell Lymphoma (a type of cancer treatable by this medication) and Rituximab depletes B cells, the studies suggest that treatment with Rituximab may also help those patients lower their risk for this disease complication.

In conclusion, the second study's research team stated: "This study indicates that rituximab could be an effective and safe treatment...for patients with primary Sjogren's syndrome."

Note: I speculate that it may be important to some patients that the addition of mouse DNA to Rituximab may create problems for those allergic to mice. Please check with your doctor if you are concerned about this type of reaction. A quick allergy test to see if you are sensitive may be a prudent precaution.

I would also like to add that, when we transfuse equine (horse) foals with antibodies (a fairly frequent occurrence), serum sickness also frequently develops. Slowing down the infusion (sometimes greatly) and allowing the foals to move around, eat etc, helps to prevent/lessen stress and this reaction. I don't know if this would be helpful for their human counterparts or not, but might be worth mentioning to your physicians in case you'd like to ask to try it.

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