When using MMF, however, she cautioned that talking to the patients about potential adverse effects is needed, including that it interferes with the efficacy of oral contraceptives and causes major fetal malformations.
For the future, she thinks that combination therapy will soon include addition of a biologic or calcineurin inhibitor (CNI) to mycophenolate.
Throw in Rituximab & Throw Out Steroids
Adding the biologic rituximab to combination therapy was the focus of Dr. Lightstone’s talk, in which she described a protocol called Rituxilup used at the Imperial College London Lupus Center that includes rituximab and eliminates oral steroids as part of the treatment regimen to treat lupus nephritis (see Table 2). The protocol has been used since January 2006 in all patients with new and relapsing lupus nephritis who are not already on steroids and do not have rapidly progressive glomerulonephritis (RPGN) or cerebral lupus.
| Table 2: Imperial College London Lupus Center Rituxilup Protocol: First-Line Treatment of Lupus Nephritis |
|---|
| Methylprednisolone (MP) (500 mg IV) + Rituximab (1 g) on Day 1 and Day 15 |
| MMF (initial dose of 500 mg twice daily) and titrate to trough levels 1.4–2.4 mg/L |
| No oral steroids used |
Of key importance in the protocol is reducing or eliminating the use of steroids to treat lupus nephritis. She cited data showing that lower doses of steroids confer similar outcomes and fewer side effects to those found with higher doses to treat lupus nephritis, as well as the most recent data showing a higher remission rate with no long-term adverse events with lower doses.2-4
These data, along with clinical experience in transplantation showing reduced rejection rates and fewer adverse events with lower doses of steroids, as well as data from uncontrolled studies showing the efficacy of rituximab in numerous case studies and registry reports, became the rationale for the protocol, she said.
Published outcomes of this protocol at 1 year show that patients do very well on the protocol.5 At a median follow-up of 37.6 months, 86% of 50 patients treated by the protocol achieved CR or PR. Of these patients, only two received oral steroids for longer than two weeks, and oral steroids were safely avoided in the effective treatment of patients with International Society of Nephrology/Renal Pathology Society (ISN/RPS) Class III, IV and V lupus nephritis.
Outcomes at five years, not yet published, also showed a high proportion of patients achieving CR, according to Dr. Lightstone, with most patients able to remain steroid free over the long term.
| Table 3: Key Findings of Rituxilup Regimen to Treat Lupus Nephritis |
|---|
| Regimen leads to remission, preservation of renal function and minimal oral steroid use in a significant proportion of patients. |
| Relapses occurred only in patients with class IV or V disease, with most patients responding to retreatment without the use of oral steroids. |
| Disease flares were common, but did not predict poor outcomes. |
| Base creatinine >120 umol/L or failure to achieve PR at six months predicted poor outcomes. |
| It is expected that minimal use of oral steroids in most patients will benefit patients in the long term in terms of cardiovascular risk and reduced side effects. |
