A British population benefited from a previously unheard of 80% complete response rate.4 Rituximab is, therefore, now on the verge of becoming the best-established alternative or adjunct treatment for lupus nephritis via this steroid-sparing trial of induction. If this observation is confirmed in subsequent trials, it will add much-needed convergent validity.
Previous data supporting rituximab use in lupus nephritis come from French registry data, non-randomized series and meta-analysis.5
All this is despite failure of rituximab to reach its primary endpoint of renal improvement in the only large placebo-controlled trial of rituximab, the LUNAR trial of 2012.6
In 2015, 26 nephrology centers in China reported 368 patients randomized to conventional intravenous CYC vs. MMF plus TAC for induction. At 24 weeks, the MMF plus TAC, called the multitarget regimen, fared better.7 This result implies a substantial benefit conferred by TAC itself, because the general perception is that MMF and CYC are close to equivalent as induction agents in lupus nephritis.
A 2016 report from Hong Kong outlined a five-year, head-to-head comparison showing TAC to be non-inferior to MMF in the role of anchor induction drug for 150 patients with lupus nephritis participating in a balanced randomization.8 In number of flares or relapses over the five years, a non-significant, but sustained, trend favoring MMF emerged.
TAC may be a better choice in pregnant patients than MMF or cyclophosphamide. Use of MMF during pregnancy is associated with an increased risk of first trimester pregnancy loss and an increased risk of congenital malformations, especially external ear and other facial abnormalities including cleft lip and palate, and anomalies of the distal limbs, heart, esophagus, kidney and nervous system.
Integrating Recent Studies
Any critique of these recent studies featuring TAC and rituximab or an attempt to integrate their data into a proscriptive scheme for prescribing for lupus nephritis must accommodate three caveats. First and most obviously, the transplant rejection context offers more restricted alternatives than the lupus nephritis context.
The second caveat arises out of the recently noted Asian–Hispanic paradox reported in Medicaid data. Gomez-Puerto et al draw attention to the fact that Asian and Hispanic patients with lupus, despite increased incidence, had better prognosis than Caucasians.9 Could Chinese populations or Asian American patients be expected to be better responders to TAC or to other regimens than the African Americans or Caucasians making up most of U.S. populations? Could the MMF-plus-TAC regimen in the Hong Kong report showing MMF and TAC equivalence have been influenced due to the Asian population being at some subtle reduced overall risk from the disease?8
