BOSTON – It took 10 years to find out that mycophenolate mofetil and azathioprine are comparable as maintenance therapies for patients with lupus nephritis, at least in a European population.
Or as the principal investigator, Dr. Frédéric A. Houssiau of Saint-Luc University Hospital in Brussels, put it, “azathioprine and MMF [mycophenolate mofetil] are equally unefficacious maintenance therapies for lupus nephritis.”
Dr. Frédéric A. Houssiau
“We really need further research, and new drugs are eagerly awaited,” Dr. Houssiau said at the annual meeting of the American College of Rheumatology.
He presented long-term follow-up results of patients with systemic lupus erythematosus (SLE) and proliferative lupus nephritis enrolled in the MAINTAIN Nephritis Trial.
The investigator-initiated trial compared MMF and azathioprine (AZA) for their ability to prevent renal flares over the long term. The immunosuppressive agents were delivered at target dose of 2 mg/kg per day for AZA or 2 g/day for MMF beginning at week 12 of the study, following induction therapy with glucocorticoids and cyclophosphamide.
At 5-year follow-up, there were fewer flares among patients treated with MMF, but the difference was not significantly superior to AZA.
In the current analysis, the authors sought to determine whether additional follow-up would reveal a difference in efficacy between the two therapies, to see what factors, if any, could predict long-term renal outcomes, and to assess whether inclusion of renal function and urinalysis in the early complete response criteria could improve the prediction of long-term outcomes.
In early 2014, they collected data on patient deaths, renal flares, renal function, and proteinuria at last follow-up, as well as current treatment, cumulated use of immunosuppressive and/or biologic agents, and serious adverse events. They also correlated long-term renal outcomes with each patient’s initial response to therapy during the first year of treatment.
Of the original 105 patients, 13 were lost to follow-up, and 5 had died, including 1 from SLE and 4 from infections. Median follow-up for the remaining 87 patients was 115 months, or 5 months shy of a decade.
At last follow-up, more than half of patients in each group were currently on glucocorticoids, and a nearly equal percentage (55% in the MMF group and 58% in the AZA group) were currently on an immunosuppressant. There were no significant differences in either the need for additional immunosuppressive therapy (36% vs. 47%, respectively), need for additional intravenous cyclophosphamide (12% vs. 22%), or need for rituximab (12% vs. 11%).
There were also no significant between-group differences in the total number of flares (19 vs. 22), proteinuric flares (12 vs. 18), or nephritic flares (6 vs. 4).
The authors also found that baseline data do not predict long-term outcomes. However, a drop in proteinuria from baseline levels early in the course of treatment was significantly predictive of good outcomes at 3, 6, and 12 months. Patients whose last creatinine levels were at or below 120% of baseline had good outcomes, whereas those with levels above 120% of baseline had poor outcomes, Dr. Houssiau said.
The investigators reported better 10-year outcomes among two sets of patients: those with an estimated glomerular filtration rate greater than 60 mL/min per 1.73 m2, compared with those with an eGFR less than 60, and patients whose last recorded serum creatinine level was less than 1.4 mg/dL when compared against those with higher values.
However, when they looked at early response criteria sets they found that including renal function and urinalysis did not add predictive value, compared with assessment of proteinuria alone at 12 months.
The findings led the authors to the conclusion that “MMF is not superior to AZA as maintenance therapy in a European population,” Dr. Houssiau said.
The study was an investigator-initiated trial without external support. Dr. Houssiau disclosed occasional consulting for eight different pharmaceutical companies.