No Difference in Infection Rates Among SLE Drugs Save

Rates of serious infection and mortality among patients with systemic lupus erythematosus (SLE)  did not depend on the immunosuppressive drug regimen they were on, investigators reported.

In a study of propensity score-matched pairs of patients, rates of serious infection and mortality didn't change whether SLE patients were new users of mycophenolate mofetil (CellCept), azathioprine, or cyclophosphamide, wrote Candace H. Feldman, MD, MPH, of Brigham and Women's Hospital in Boston, and colleagues, in Arthritis & Rheumatology.

It's well known that patients with SLE face an increased risk of developing serious infections that could lead to hospitalizations and even death. But uncertainty exists as to whether infection rates differ according to the various immunosuppressive drug regimens SLE patients undergo, Feldman's groups pointed out.

The authors used insurance claims data from the Medicaid Analytic eXtract database for Medicaid enrollees to assess whether there were differences in the rates of serious infection among SLE patient initiating mycophenolate (CellCept) compared with azathioprine, as well as those initiating mycophenolate compared with cyclophosphamide.

These agents were selected for study because they are the most commonly used medications for treating moderate-to-severe SLE (other than hydroxychloroquine and corticosteroids) and are often used interchangeably.

Feldman and her colleagues studied 1,350 propensity score-matched pairs of patients in whom mycophenolate and azathioprine treatments had been newly initiated, as well as 674 pairs of mycophenolate and cyclophosphamide patients. They estimated propensity scores for the patients receiving mycophenolate versus those receiving azathioprine, as well as those receiving mycophenolate versus cyclophosphamide, based on sociodemographic, comorbidity, and medication use information.
For both drug comparisons, they determined rates of first serious infection as well as all-cause mortality over 6- and 12-month periods.

First serious infection was defined as a hospital discharge diagnosis ICD-9 code for bacterial infection, as well as fungal, viral, and mycobacterial infections.

For the mycophenolate/azathioprine comparison, the 6-month intention-to-treat (ITT) analysis determined that the incident rate of first hospitalized infection per 100 person-years was 14.6 (95% CI 11.6-17.6) among mycophenolate new users and 15.2 (95% CI 12.9-18.3) among azathioprine new users.

More than 90% of the infections in both treatment groups were bacterial and there was no significant difference in time to infection. Additionally, there was no significant difference in infection rates in the 12-month ITT analysis.

As for the mycophenolate/cyclophosphamide group, a 6-month ITT analysis comparing the two found that the incident rates of first hospitalized infection per 100 person-years were 24.1 (95% CI 18.6-29.7) among new mycophenolate users and 24.6 (95% CI 19.0-30.2) among new cyclophosphamide users. As with the mycophenolate/azathioprine comparison group, over 90% of infections were bacterial, and there were no significant differences in infection rates in the 12-month ITT analysis.
While the researchers observed no differences in serious infection rates based on their analyses, "we found high rates of serious infections associated with use of all three of the immunosuppressive medications examined.

Therefore, they suggested that "the high burden of serious infections among SLE patients receiving these medications overall is important to consider."

This study has the potential to help physicians guide clinical decisions concerning these three drugs, Feldman's group concluded, adding that their findings suggest that "concerns about differential infection risks may not need to influence physician and patient choice between mycophenolate versus azathioprine and mycophenolate versus cyclophosphamide, even in a population highly susceptible to adverse outcomes."

While the study was the largest head-to-head population-based comparative effectiveness study examining this subject, the authors wrote, "it lacks power to examine specific infection subtypes, as well as the effect of immunosuppressive dosages on these rates." They also pointed out that while the study compared risk of infection in the short term, further study is needed to analyze the risk associated with long-term use of these medications.