Flares of disease activity are a serious complication for people with lupus nephritis (LN), which causes inflammation, protein spilling into the body rather than being filtered by the kidneys, and damage in the kidneys and renal system. LN usually is treated with aggressive immunosuppressive medications, along with corticosteroids (steroids). The first part of the treatment, which requires the highest doses of immunosuppressive medication, is called "induction therapy." When the LN flare becomes controlled, medication usually can be reduced to lower doses; this is called "maintenance therapy."
How was the study conducted?
Patients were treated for 24 weeks with either MMF or CY, in addition to prednisone, a steroid. Whether a person received MMF or CY was determined by chance; this is called "random assignment." At the start of the study there were 185 patients in each group, and the make-up of the groups was similar in terms of the mix of men and women, age, race, types of lupus symptoms, and degree of kidney damage. This is important to know because if other factors that might affect the outcome were not equal between the groups, it would be harder to compare the treatments. The average prednisone doses were the same for the two groups, and these doses were steadily decreased
("tapered") over the six-month induction treatment period. By the end of the 24-week period, 64 patients had dropped out of the study, leaving 150 in the MMF group and 156 in the CY group.
When patients of African/mixed race or Hispanic descent were evaluated, a much larger percentage of them improved with MMF (60.4% and 60.9%, respectively) than with CY (38.5% and 38.8%, respectively). This sub-group of patients did better overall on MMF than the complete MMF group did, and they also fared worse on CY than the complete CY group. This is important because African Americans and Hispanics with lupus seem to develop more serious complications in general, and African Americans with lupus also have a higher rate of kidney failure.
Most of the patients in each group developed one or more side effects (96.2% for MMF, 95% for CY). However, there were more side effects overall in the CY patients than the MMF patients: 51 (27.7%) patients in the MMF group and
41 (22.8%) of the patients in the CY group had at least one serious side effect. Both groups reported having the same kinds of problems, the most common being infections and gastrointestinal disorders (nausea and vomiting). Diarrhea was more common in patients who took MMF, whereas hair loss (alopecia) occurred mostly in CY patients. Twenty-four MMF and 13 CY patients had to stop participating in the study because of side effects.
Because the study was only 24 weeks long, the researchers were not able to note any side effects that could emerge at a later date as a result of taking one of these medicines. They hope to learn more about these possible longer term side effects by continuing to study these same patients during their maintenance treatment period, which will be handled as a different phase of this study. It might be helpful to know what percentage of patients from each racial or ethnic background received MMF vs cyclophosphamide and how race or ethnicity might have affected the side effects. For example, the efficacy data favor people from African/mixed or Hispanic descent. These patients might like to know how many side effects people from their background had on each treatment. Also, by assessing results only after 24 weeks, the researchers did not take into account how quickly patients responded, which might have been different between the two treatments.
This was one of the largest international studies on LN that compared MMF and CY. Although MMF and CY seemed to work equally well, there are other factors that need to be considered when comparing the two medicines and deciding on treatment. As a pill, MMF is much more convenient for patients to take than IV CY, which needs to be given in a doctor's office or by a home-care nurse. Also, MMF has not been shown to have long-term effects on fertility, which can be important for women of child-bearing age, as well as for men who want a family. And finally, for Hispanic and African American patients, MMF seems to provide more effective treatment.