Low-Dose Combination May Be Effective for Refractory Lupus Nephritis

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ATLANTA—A low-dose combination of mycophenolate mofetil (MMF) and tacrolimus (TAC) may be a viable option for treating refractory lupus nephritis, according to a new study by Chinese investigators.

This regimen is well tolerated and resulted in few serious adverse events, the researchers reported at the 2010 American College of Rheumatology Annual Scientific Meeting.

Despite the availability of newer treatment options such as MMF and B cell depletion agents, the response rate to initial treatment of lupus nephritis has not significant improved in recent years.  Today, lupus nephritis still carries significant morbidity and mortality. 

Studies suggest that up to 25% of patients with active and serious lupus nephritis may not respond to initial immunosuppressive regimens, especially those patients with impaired renal function at presentation. Studies also have shown that failure to respond to immunosuppressive treatment in the first year after diagnosis may predict further renal function deterioration and end- stage renal disease.

Treatment modalities for refractory lupus nephritis have included intravenous immunoglobulin, MMF, cyclosporine A, TAC and rituximab.  However, none of these agents or combinations of them has been able to help all patients, and a certain proportion of patients can still remain unresponsive.  A recent randomized controlled trial in mixed class IV/V lupus nephritis patients showed that a combination of MMF and TAC was more effective than pulse cyclophosphamide (CYC) with high dose steroids in terms of short-term efficacy (9 months).

Researchers at Tuen Mun Hospital in Hong Kong evaluated the efficacy and toxicity of a low-dose combination MMF and TAC for the treatment of refractory nephritis. The study enrolled 11 patients with a mean age of 35.7 years who failed to respond to at least two immunosuppressive regimens consisting of high-dose corticosteroids in combination with one other immunosuppressive agent.

The combination used in the study consisted of 1 g per day of MMF and 4 mg a day of TAC in two divided doses.  The doses of MMF and TAC could be reduced if any serious adverse events were reported.  All the patients were followed prospectively for 12 months for various clinical and renal parameters of lupus nephritis in terms of response and adverse events.

The mean systemic lupus erythematosus (SLE) duration was 106 months at study entry. 

Five patients had completed 12 months of follow-up. Researchers observed significant improvements in proteinuria and urinary sediments in four of them. Improvements occurred  approximately four months after the start of treatment. At 12 months, four patients achieved a proteinuria below 1 g a day and improved creatinine clearance.

“This is a new regimen and the response was quite good and most of the patients had improvements in terms of proteinuria and stabilization of renal function,” said lead investigator Chi Chiu Mok, MD, Chief of Rheumatology at Tuen Mun Hospital, Hong Kong.  “Only one to two subjects did not respond to this regimen.”

The only complication associated with the combination treatment was minor infections. One patient reported leg cramps. “These findings are good news because these patients were already refractory to steroids and two other immunosuppressive agents and so there are not many choices that are left for them,” Dr. Mok told Renal & Urology News. “We noticed most of the patients had some improvement and there was no further deterioration of kidney function. “For refractory lupus nephritis, if the patient does not respond to treatment the renal function will deteriorate with time. We found that most patients tolerated this protocol very well.”

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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