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Glomerulonephritis & Lupus

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New drugs: A New Option for Lupus Induced Kidney Disease

By admin

Published: August 7, 2009

rituximab..

A new study published in March 2009 comparing the standard treatment of lupus nephritis i.e corticosteroids and cyclophosphamide vs rituximab was published in the clinical journal of the american society of nephrology.

Cyclophosphamide is considered a main stay of chemotherapy where it functions as an ” alkylating agent” which is simply a way to express that it binds to DNA (the code that determines the function of the individual cells within the body) and destroys it.

If it were capable of destroying only cancer cells or cells of the immune system involved in lupus then it would be a perfect drug a magic bullet, unfortunately its side effects prove otherwise they include nausea, loss of hair, bone marrow suppression, predisposition to infections, sterility and ironically, with accumulating, doses even cancer. However studies have shown that up to 70% of lupus patients will respond to this drug and the side effects are not guaranteed to occur hence its continued use. Steroids on the other hand are well known to a variety of patients and come with their own problems. The price to be paid is weight gain predisposition to diabetes and recurrent infections, fluid retention, skin changes, hair growth and loss of bone mass to name a few. Steroids however are highly effective at suppressing the entire immune system by turning off the signal in between the sentinel cells that protect the body by searching for foreign invaders on a daily basis. When these cells are unable to talk to each other effectively the immune response is blunted and hence the attack of the immune system against its own body is also blunted. This leads directly to their efficacy in lupus where the immune system is overactive and a major part of the problem.

The fact is however that depending on the genetic make up of each individual patient with lupus and kidney disease these drugs may not work at all to prevent progression of the disease to the end stage. This has led to the search for alternative therapies such as rituximab.

Rituximab is a monoclonal chimeric antibody that targets b cells. Sounds almost like that magic bullet doesn’t it?

This drug was designed to perform one task. Locate the cells causing the problem in autoimmune disease (the B cell) and kill it. Unfortunately B cells are also necessary for the normal functioning of the immune system so its expected that there would be increased risk of infection after taking the drug. But the hope is that there would be much less side effects associated with its therapy than the older regime.

This study had 20 test subjects nineteen women and one man side effects included five infections. A complete resolution of kidney disease was seen in 60% of the patients. The investigators concluded that rituximab is an interesting therapeutic option in relapsing or refractory lupus nephritis. The study is small however and the findings should be noted, however additional studies will be needed in the future before the drug can become a mainstay of therapy.

Unfortunately the cost of rituximab in jamaica is an issue. The drug is priced out of the reach of many people as a course costs in the region of two hundred thousand dollars.

The verdict? In my opinion try standard therapy first rituximab should only be used as a last line of defense in a patient that has tried everything already and it hasn’t worked. Be aware that you are entering unknown territory to some extent.

EDIT: 14th October 2009.

The FDA has issued an advisory re: the use of Rituxan to treat Lupus. The advisory follows the death of two patients who recieved the drug for treatment of lupus. They had a rare complication of therapy known as pleomorphic multifocal leucoencephalopathy or PML.

About Roger:
Dr. Roger Smith is a nephrologist currently employed to the government of Jamaica. He is the Nephrologist in charge of Spanish Town Dialysis Unit. His interests are lupus nephritis and other glomerulopathies. He was previously a lecturer in Nephrology at the University of the West Indies in the Department of Internal Medicine and Coordinator of the Urogenital Module before moving into private and government practice.