Mycophenolate mofetil was superior to azathioprine in preventing treatment failure in 227 lupus nephritis patients who initially responded to induction therapy, according to a randomized, double-blind comparison of the drugs’ efficacy during a 36-month maintenance phase of treatment.
The study’s participants were selected from a group of 370 lupus nephritis patients that received induction therapy in the form of mycophenolate mofetil (MMF) or intravenous cyclophosphamide (IVC) for 24 weeks; there was no difference in the efficacy of these two drugs.
All patients entered the study with biopsy-proven class III-V lupus nephritis and laboratory tests consistent with active nephritis, including evidence of an active urine sediment, proteinuria greater than or equal to 1 g/day or elevated serum creatinine (greater than 1.3 mg/dL). Patients with class III or V lupus nephritis were required to have higher levels of proteinuria (greater than or equal to 2 g/day) or serum creatinine greater than 1.3 mg/dL. Only patients who met prespecified criteria for a complete or partial renal response after 24 weeks of induction therapy and were adjudicated as responders by the clinical endpoints committee were advanced into the maintenance phase of the trial. The primary outcome measure in the maintenance phase was the time to treatment failure (TF), defined by any of the following criteria: death, end-stage renal disease, sustained doubling of serum creatinine, or renal flare and requirement for rescue therapy.
Among the patients who participated in the induction phase of the trial, non-Hispanic ethnicity was associated with a higher likelihood of complete remission.
Various characteristics of the study’s participants were associated with greater likelihood of treatment failure. These included: anti–double-stranded DNA (anti-dsDNA) at trial entry, failure to reduce anti-dsDNA within 8 weeks, and failure to reduce urine protein:creatinine ratio (UP/C) by greater than or equal to 25% within 8 weeks (Lupus Sci. Med. 2015 [doi:10.1136/lupus-2015-000089]).
For patients who participated in the maintenance phase, baseline estimated glomerular filtration rate (eGFR) greater than or equal to 90 mL/min/1.73 m2, and UP/C greater than or equal to 1 at the end of induction were independently associated with complete remission during the maintenance phase.
Among the study’s other findings for patients who participated in maintenance therapy were that lack of treatment with antimalarials, failure to reduce anti-dsDNA or UP/C within the first 8 weeks of induction therapy, and anti-dsDNA positivity at the end of induction were independently associated with TF.
“Although our findings contribute to the understanding of predictors of renal outcomes in lupus nephritis, we believe that the associations described in this study are not strong enough to directly impact therapeutic decision making in individual patients in the clinic,” noted Dr. Maria Dall’Era of the University of California, San Francisco, and her colleagues. “Better biomarkers are needed to achieve this important goal. Lastly, in future controlled trials of lupus nephritis, studying the factors identified in our present analysis in a prespecified fashion might serve to further elucidate their association with renal response to treatment.”
The researchers declared no conflicts of interest.