COMMENTARY

Reassessing Levamisole Use in Children With Frequently Relapsing Nephrotic Syndrome

Tejas P. Desai, MD

Disclosures

June 29, 2018

Glomerulonephritis (GN) is one of the hottest areas of research in nephrology. Despite representing a significant minority of the patients many private practitioners see, academic centers continue to make strides in studying various immunosuppressive therapies. Some years ago, rituximab was the "darling" of many GN trials, used alone and in various combinations with new and old agents.

Indeed, the recent #EUVAS conference in Italy (hosted by the European Vasculitis Society, April 19-21, 2018; twitter.com/hashtag/EUVAS) introduced us to newer agents such as avacopan, mepolizumab, and tocilizumab. While these agents are new players in the game, an older agent that deserves our attention is levamisole. Levamisole is certainly not a new agent, but a recent randomized controlled trial warrants a new look at this agent by us.

While most glomerulonephritis trials focus on adults, levamisole has been studied recently in pediatric patients. These patients are uniformly placed on steroid therapy for initial management of glomerular injury. While steroids are generally quite effective, the duration of dosing puts many children at risk for long-term complications. These complications, in both children and adults, drive the search for alternative immunosuppressive agents.

The Study

Researchers in Europe and India have decided to revisit levamisole, a drug considered to be the least toxic and least expensive steroid alternative. In a randomized clinical trial, this medication was administered to children, who experienced a complete remission of nephrotic syndrome (whether steroid-free or steroid-dependent).[1] The primary outcome was the time to relapse after randomization. Levamisole significantly lowered the risk for relapse (hazard ratio, 0.22; 95% confidence interval, 0.11-0.43) compared with placebo, and the earliest therapeutic response to levamisole was seen beginning at 100 days.

These results are tremendously important because levamisole frees pediatric patients from a childhood of steroid-induced complications, some of which are permanent and/or life-altering. Adverse effects, the main hesitation for continuing steroids, were relatively benign and reversible. The main complication of treatment with levamisole was reversible neutropenia (four out of 50 patients); none of the episodes required termination of treatment.

Viewpoint

In our quest to free patients of all ages from the devastating chronic effects of steroids, many new and formerly dismissed agents are being considered or reconsidered as viable therapeutic options. Levamisole has garnered medical skepticism, as it has been implicated as an ingredient (pollutant) in diluting illicit drugs for greater profits.[2]

Still, it is important to recognize that levamisole has an established purpose (as a veterinary anthelmintic agent [3]) and may serve another benefit against glomerular relapse. If it can work in children, can it have a similar effect in adults? If so, then it should be mentioned with newer agents as an effective alternative to steroids. Perhaps, agents such as levamisole may hold enough promise and effectiveness to replace steroids altogether and provide patients with a permanent freedom from the ravages steroids impart. Tell us what you think in the comments below.

Follow Tejas P. Desai, MD, on Twitter: @nephondemand

Follow Medscape Nephrology on Twitter for more nephrology news: @MedscapeKidney

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