A study amongst the pediatric steroid resistant nephrotic syndromes, showed high remission rates and less side effects with Tacrolimus versus Cylophosphamide group  which has been the treatment choice since long.

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Tacrolimus (Prograf) was better than cyclophosphamide at inducing and sustaining remission of proteinuria in pediatric patients with steroid-resistant nephrotic syndrome, an Indian study showed.

After six months of treatment, tacrolimus resulted in a 36.6% absolute increase in the rate of complete or partial remission, according to Ashima Gulati, of the All India Institute of Medical Sciences in New Delhi.

The number needed to treat was 2.7, she reported at the American Society of Nephrology here.

Tacrolimus also carried less risk of treatment failure and serious infection.

“Tacrolimus should be the preferred therapy for patients with idiopathic steroid-resistant nephrotic syndrome,” Gulati said.

Treatment of these patients can be challenging, she said, and the most appropriate therapy remains a topic of discussion. The most evaluated treatments for steroid-resistant nephrotic syndrome are cyclosporine and IV cyclophosphamide, accompanied by low-dose prednisolone.

IV cyclophosphamide has yielded success rates of 25% to 60% in various studies. Its advantages include the abbreviated six-month regimen and low cost, but those come at the expense of long-term safety concerns, particularly gonadotoxicity and infections.

Cyclosporine has been shown to be highly effective, with success rates of 70% to 80%. But there are issues with the need for prolonged therapy, risks of relapse after discontinuation, nephrotoxicity, and high cost.

So alternatives are being explored, Gulati said.

Although cyclosporine has been the most commonly tested agent, the preferred calcineurin inhibitor is tacrolimus because of a better safety profile, she said.

In a small, single-center, randomized trial, Gulati’s group found that tacrolimus had efficacy similar to that of cyclosporine, but with a better side effect profile.

That led to its evaluation in a larger study compared with IV cyclophosphamide. The trial was conducted at five Indian centers in 131 children ages 2 to 16 who had idiopathic steroid-resistant nephrotic syndrome with minimal change disease, focal segmental glomerulosclerosis, or mesangial proliferation on biopsy.

The patients were randomized to tacrolimus (0.1 to 0.15 mg/kg/day orally) for 12 months or six monthly infusions of IV cyclophosphamide (500 mg/m2). All patients also received prednisolone every other day with the dose tapered from 1.5 mg/kg to 0.5 mg/kg by one year.

Complete remission of proteinuria was defined as a urinary protein/creatinine ratio less than 0.2. Partial remission was defined as a ratio of 0.2 to 2.0 with a serum albumin greater than 2.5 g/dL, and no edema. Nonresponse was a ratio greater than 2.0 accompanied by edema or low albumin.

The difference in the primary endpoint of complete or partial remission of proteinuria was driven by a significant increase in the percentage of patients with complete remission in the tacrolimus group . There was no difference in partial remission.

Tacrolimus was also associated with a lower proportion of treatment failures . Most of the failures in both groups were due to nonresponse, although there were also several withdrawals of therapy and serious infections in the cyclophosphamide group.

Among the patients who had complete or partial remission at six months, the effect was sustained at one year in 73.1% of patients taking tacrolimus .Also, the rate of non-nephrotic proteinuria was lower in the tacrolimus group. There were no cases of hyperglycemia, neutropenia, or alopecia during the study.

On average, renal function did not change during the course of the study, with no between-group difference.

Serious infections were more common with cyclophosphamide.

Philip Marsden, MD, of the University of Toronto, said that treatment of steroid-resistant nephrotic syndrome has always been a challenge for pediatric nephrologists, and that conducting trials has been difficult because there are not many patients with the condition.

Marsden, who served as one of the moderators of the late-breaking clinical trials session at which Gulati reported the results, said that the study did a good job at finding patients and “provided important new stepwise information that will inform future trials.”

Ref: http://www.medpagetoday.com/MeetingCoverage/ASN/29675?utm_source=WC&utm_medium=email&utm_campaign=Meeting_Roundup_ASN