In the treatment of children with idiopathic steroid-sensitive nephrotic syndrome, mycophenolate mofetil demonstrates noninferiority to prednisone in maintaining remission and reducing subsequent relapse, with the added benefit of reduced glucocorticoid-related toxic effects, according to the open-label phase III INTENT trial.
In a cohort of paediatric patients who had achieved glucocorticoid-induced remission during initial treatment, the primary endpoint of the occurrence of a treated relapse during the 24-months of follow-up did not significantly differ between mycophenolate mofetil and prednisone (79.1 percent vs 74.8 percent; difference, 4.3 percent, 90 percent confidence interval [CI], −4.2 to 12.7; p=0.019). [Lancet Child Adolesc Health 2026;doi:10.1016/S2352-4642(25)00373-6]
No significant between-group differences were observed in the incidence of frequently relapsing nephrotic syndrome (45.6 percent with mycophenolate mofetil vs 43 percent with prednisone), the number of patients who received a glucocorticoid-sparing alternative treatment to prevent further relapses (56.9 percent vs 55 percent), and the time to first glucocorticoid-sparing alternative (median 666 vs 712 days).
“The glucocorticoid-sparing effect of initial mycophenolate mofetil therapy persisted through the final follow-up, 24 months after the end of initial treatment,” the investigators said.
“The mean cumulative prednisone dose in the mycophenolate mofetil group was lower than in the prednisone group (4,605 vs 6,586 mg/m2 body surface area), primarily due to substantial steroid savings during initial therapy,” they added.
Safety
After 12 weeks of treatment, the mycophenolate mofetil group had fewer glucocorticoid-related side-effects, including arterial hypertension (59.1 percent vs 87.1 percent), lower BMI (BMI Z score, 0.16 vs 1.41), and psychological abnormalities (27.8 percent vs 57.9 percent), compared with the prednisone group.
As for potential mycophenolate mofetil-associated side-effects, the rate of any infections was 69.9 percent in the mycophenolate mofetil group vs 55.6 percent in the prednisone group (69.9 vs 55.6 percent). The percentage of patients who had any gastrointestinal disorders was 16.5 percent vs 9.8 percent, respectively.
“There were more serious adverse events in the prednisone group than in the mycophenolate mofetil group (11 vs seven events), and these included infections, injuries, hyperglycaemia, headaches, and disorders of the kidneys and urinary tract,” the investigators noted. “All serious adverse events resolved completely.”
Steroid-sparing medication
“To our knowledge, INTENT is the first randomised trial to evaluate a glucocorticoid-sparing alternative medication in the treatment of idiopathic nephrotic syndrome following remission,” the investigators said. “The findings could modify the initial standard of care for patients with steroid-sensitive nephrotic syndrome.”
They noted that having a glucocorticoid-sparing alternative medication may be relevant to patients and their families, for whom prednisone-related side-effects represent a substantial burden. “Reducing these side-effects is one of patients and their families’ highest priorities.”
INTENT
INTENT was a multicentre, open-label, noninferiority, phase III trial conducted at 37 sites across Germany. A total pf 272 patients aged 1–10 years with a first episode of steroid-sensitive nephrotic syndrome were randomly assigned to receive treatment with either mycophenolate mofetil (n=136) or prednisone (n=136), after remission induced by prednisone or prednisolone at a dose of 60 mg/m2 body surface area (maximum 80 mg/day) within 28 days.
Mycophenolate mofetil was given at 1,200 mg/m2 body surface area per day, twice daily, as a suspension (200 mg/mL) for 12 weeks. Additionally, prednisone was administered at 40 mg/m² body surface area (maximum 60 mg) every other day in a single morning dose for the first 2 weeks in order to bridge the gap until adequate exposure to mycophenolic acid had been achieved.
In the control group, prednisone was administered at 60 mg/m² body surface area per day (maximum 80 mg) once, twice, or three times daily for 6 weeks. Thereafter, prednisone was given for a further 6 weeks at 40 mg/m² body surface area (maximum 60 mg) once daily in the morning on alternate days.
The primary endpoint of treated relapse during the 24-months of follow-up was evaluated in the modified intention-to-treat population (n=269, median age 4 years, 64 percent boys). Clinical and demographic characteristics at randomisation were similar between the two groups.
A relapse was defined as the recurrence of proteinuria for 3 consecutive days, a urine protein-to-creatinine ratio of ≥2 g/g in the first or second morning urine sample, or urine protein excretion of ≥40 mg/m² body surface area per h in a urine sample collected over at least 12 h.