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For very young children with nephrotic syndrome, longer initial treatment with prednisone didn't offer much benefit, a researcher reported.

In a randomized controlled trial of 172 patients ages 1 to 4 years, relapse rates were no better in those who received a 6-month course of prednisone versus those on a 3-month course, reported Aditi Sinha, MD, MBBS, PhD, of All India Institute of Medical Sciences in New Delhi.

Patients in both treatment arms were given standard therapy for their initial episode of nephrotic syndrome, consisting of 60 mg/m² of oral prednisone -- either in tablet or syrup form -- for 6 weeks, followed by 40 mg/m² on alternate days for an additional 6 weeks, Sinha said in her presentation at the American Society of Nephrology's virtual Kidney Week.

Randomization then occurred, with half of these patients receiving a prolonged steroid therapy course, consisting of a tapering of prednisone: 30 mg/m² on alternate days for 4 weeks, followed by 20 mg/m² on alternate days for 4 weeks, and concluding with 10 mg/m² on alternate days for the last 4 weeks. In the comparator group, no further therapy was given after randomization.

In the intention-to-treat analysis, those on the prolonged therapy course didn't see any significant improvement in the study's primary endpoint of sustained remission at 1 year, at 39.1% versus 28.2% with the standard 3-month therapy (P=0.11).

Sinha pointed out that trends did in fact favor prolonged therapy during the initial months of follow-up, but this wasn't statistically different after 12 months. After 2 years, only 25.6% of those on prolonged therapy sustained remission versus 18.6% on standard therapy.

Although those on prolonged therapy saw a numerically longer time to first relapse, at 7.4 months versus 4.2 months, the difference was not significantly different (HR 0.76, 95% CI 0.54-1.07).

Median time to frequent relapses was also numerically longer in the prolonged therapy group -- 21.8 months versus 13.8 months -- but likewise wasn't statistically significant (HR 0.78, 95% CI 0.52-1.18).

"You do see that there is postponement of the first relapse in the extended therapy limb. And while ... not achieving statistical significance, the P values are in the range of 0.1 and 0.15 -- and that's what bothers us," Sinha explained.

"We do believe, however, that even inclusion into current meta-analyses for at least the rate of treatment relapses -- really the clinically meaningful outcome of interest -- is not going to change," she added.

"This study and [prior] randomized controlled trials across two continents in the last decade have shown that probably 2 to 3 months [of therapy] is sufficient," Sinha emphasized. "We do not need to expose them to more corticosteroid toxicity."

The multicenter open-label trial included 172 patients ages 1 to 4 years with newly diagnosed steroid-sensitive nephrotic syndrome. All achieved complete remission by week 6 of therapy with daily 60-mg/m² prednisone. Patients were excluded if they had secondary nephrotic syndrome, an estimated glomerular filtration rate below 75 mL/min/1.73 m², gross hematuria, or had ever been treated with corticosteroids for nephrotic syndrome, or treated with corticosteroids for something else within 12 weeks at a dose higher than 1 mg/kg for more than 14 days. Patients were also excluded if they showed steroid resistance during the initial therapy phase.

Rates of adverse events were similar between the two treatment arms, including for pneumonia (21% with prolonged therapy vs 22.3% with standard therapy), peritonitis (2.4% vs 0%), septic shock (1.2% vs 0%), malaria (3.6% vs 1.2%), and varicella (2.4% vs 2.4%). A total of 195 upper respiratory infections were reported in the prolonged therapy group versus 179 in the standard therapy group.

There was also a similar rate of corticosteroid-associated adverse events between the groups, including for hypertension, Cushingoid appearance, hirsutism, and ophthalmological changes.

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