A few months ago, I reviewed a Kidney International placebo-controlled trial of levamisole in children with steroid-dependent nephrotic syndrome.[1] Some of you may recall my overall enthusiasm for the trial. In brief, levamisole was effective at prolonging relapse in children who were chained to using prednisone indefinitely. I was excited, in part because the data revealed a possibly inexpensive way to circumvent the deleterious side effects of chronic steroid therapy and offer meaningful preservation of renal function.
Surprisingly, many of my pediatric nephrology friends in the United States had not tried levamisole. It wasn't in their armamentarium against this devastating disease.
So I was happy to know that another randomized controlled trial was published addressing the same question: Can "steroid-dependent" children with nephrotic syndrome be freed from their steroid dependence? Surely, one of the two medications studied in this JAMA Pediatrics trial would be in their "utility belt."[2]
Study Outcomes
The trial randomly assigned 120 children who were steroid-dependent in maintaining remission from nephrotic syndrome. The children had to be in remission, defined as an absence of proteinuria and an estimated glomerular filtration rate (eGFR) greater than 80 mL/min/1.73 m2.
Children were given either oral tacrolimus daily (the control arm) or two doses of rituximab spread over as many weeks. Both arms received alternate-day dosing of a steroid and the study followed their progress over the successive 12 months. Relapse of nephrotic syndrome was defined as having 3+ proteinuria or more on three successive urinalyses (the primary endpoint).
Even though children in both arms were exposed to a lower cumulative dose of steroids than had they been maintained exclusively on steroids, those in the rituximab arm maintained remission longer than those in the tacrolimus arm (90% vs 63%; P < .001; odds ratio [remission with rituximab], 5.21; 95% confidence interval, 1.93-14.07). The split in the trajectory of remission in each arm first appears around 10 weeks of treatment.
Perhaps equally important:
The children in the rituximab arm received an impressively lower cumulative dose of steroids than their tacrolimus counterparts (25.8 mg/kg vs 86.3 mg/kg)
Only two doses of rituximab were required versus daily oral tacrolimus administration
Both are tremendous advantages for rituximab therapy in terms of minimizing steroid-induced adverse effects and improving treatment adherence.
What Are Your Thoughts on Rituximab?
I was surprised once again when I approached my pediatric colleagues and asked them about rituximab. It seems that many of them consider mycophenolate or cyclosporine as their favorite steroid-sparing agent in this population. Levamisole seems to be used to a greater degree in Asian nations, while mycophenolate seems to have gained favor among American and Western European pediatric nephrologists.
Rituximab, however, was the least frequently used as a steroid-substitute. Could this be because of the recentness of these findings? Perhaps they haven't percolated into the community as quickly as I anticipated. Does the cost of rituximab negate any positive trial results? Alternatively, is there a therapeutic feature of rituximab that doesn't make it suitable for this population of children?
What do you think? Share your perspective in the comments below and see what others think by visiting my post on Twitter.
Follow Tejas P. Desai, MD, on Twitter: @nephondemand
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Any views expressed above are the author's own and do not necessarily reflect the views of WebMD or Medscape.
Cite this: Tejas P. Desai. Rituximab Over Tacrolimus in Steroid-Dependent Nephrotic Syndrome? - Medscape - Nov 30, 2018.
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