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What is the topic?
Children and adolescents who develop lupus (pediatric-onset lupus) may have severe symptoms, kidney disease being especially common. To keep lupus in control and to prevent kidney damage, these young people may have to take several medications in combination, including strong immunosuppressant drugs, such as cyclophosphamide (a form of chemotherapy) and steroids, such as prednisone. Both cyclophosphamide and steroids can have serious side effects when taken over long periods of time, especially in younger individuals whose bodies are still developing.
What did the researchers hope to learn?
Tacrolimus (trade name: Prograf®, Protopic®) is an immunosuppressant drug that helps control inflammation. It was originally developed and approved to help prevent rejection of the new organ in transplant patients, but in recent years tacrolimus has been used to treat adults with lupus or rheumatoid arthritis. The researchers wanted to know if tacrolimus could be used safely to control lupus nephritis in pediatric-onset lupus patients with long-standing disease.
Who was studied?
The researchers studied six individuals who had been diagnosed with pediatric-onset lupus and who came to the same hospital in Japan for treatment during a lupus flare. At the time the study began, the participants ranged in age from 14 to 23. Five were teenage girls or young women in their early 20s; one was a young man in his early 20s. All six had been diagnosed before they were 14 years old, and had lupus for at least three years when they began the study. They also all had lupus nephritis, and had previously used a combination of prednisone and another immunosuppressive drug (cyclosporine A, cyclophosphamide, or mizorbine) to treat flares.
How were the studies conducted?
The study participants began treatment with tacrolimus and took the medication for at least six months (the researchers pointed out that tacrolimus has been given to other lupus patients for a one- to two-year period). The participants also continued to take prednisone during the study period, either in the same dose as they had before or a lower amount if they were getting better. Once a month, the researchers took a blood sample from the participants and measured the level of tacrolimus in the blood. At the start of the study and then again after one, three, and six months of treatment the researchers also compared blood levels of certain antibodies, proteins, and other chemicals that can indicate lupus kidney disease activity,. Lupus disease activity was measured at those times as well. This study did not have a control group taking a placebo (a substance that has no ingredient to treat the disease), and the study was not blinded, meaning that the participants, their family members, and the medical staff all knew that tacrolimus was being used.
What did the researchers find?
Tacrolimus appeared to work well in all of the participants, with some improvement in their lupus activity scores at the end of the first month. At three months and six months, the participants also had decreased levels of immune proteins (antibodies) and proteins that are seen in kidney disease. Five of the six individuals were able to reduce their prednisone doses; the only person who continued at the same prednisone dose after six months was the one who had the most advanced kidney disease at the time the study began. Although she did show some improvement in other measures, this was considered only a "partial response."
Tacrolimus also appeared to be well tolerated. None of the participants had to stop taking the medicine, nor were there any major side effects. Infections are a serious concern for anyone taking immunosuppressant drugs, but none of the six individuals taking tacrolimus in this study had even a minor infection. There were no reports of low white blood cell counts or other blood complications, or stomach or liver problems -- all of which can be related to immunosuppressant drugs. Although the level of tacrolimus in the participants’ blood varied greatly -- with some having more than three times the amount as others -- the researchers found that there was no relationship between the level of tacrolimus in the blood and its effectiveness or side effects.
What were the limitations of the studies?
The study had a very small sample size and the participants were all Japanese, so these results might not apply to all people with pediatric-onset lupus. Also, the study only followed the participants during the course of their treatment; although there were no serious side effects in that time period, there is no way to know if taking tacrolimus might cause problems later on in their lives.
What do the results mean for you?
As a pilot study, this research is a promising first step in a much bigger process that will be required to see how well tacrolimus works in individuals with pediatric-onset lupus that involves the kidneys. This is one of a number of studies in which tacrolimus has shown preliminary good results for treating lupus and it does appear that further studies are warranted. The rapid positive response to tacrolimus seen in the study participants, combined with the fact that there did not appear to be any serious side effects from taking tacrolimus for six months, makes it a possible treatment for lupus nephritis flares; to be sure, however, a direct comparison to the other medications currently being used would be necessary. Identification of a potential new treatment is especially encouraging for younger lupus patients, who may have serious kidney disease and may need to be treated with strong therapies many times over the course of their lifetime.
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