Sequential administration of paricalcitol followed by IL-17 blockade for progressive refractory IgA nephropathy patients

Abstract

There is no established treatment for progressive IgA nephropathy refractory to steroids and immunosuppressant drugs (r-IgAN). Interleukin 17 (IL-17) blockade has garnered interest in immune-mediated diseases involving the gut-kidney axis. However, single IL-17A inhibition induced paradoxical effects in patients with Crohn’s disease and some cases of de novo glomerulonephritis, possibly due to the complete Th1 cell response, along with the concomitant downregulation of regulatory T cells (Tregs). Seven r-IgAN patients were treated with at least six months of oral paricalcitol, followed by the addition of subcutaneous anti-IL-17A (secukinumab). After a mean follow-up of 28 months, proteinuria decreased by 71% (95% CI: 56–87), P < 0.001. One patient started dialysis, while the annual eGFR decline in the remaining patients [mean (95% CI)] was reduced by 4.9 mL/min/1.73 m2 (95% CI: 0.1–9.7), P = 0.046. Circulating Th1, Th17, and Treg cells remained stable, but Th2 cells decreased, modifying the Th1/Th2 ratio. Intriguingly, accumulation of circulating Th17.1 cells was observed. This novel sequential therapy appears to optimize renal advantages in patients with r-IgAN and elicit alterations in potentially pathogenic T helper cells.

Advancements in understanding the role of intestinal dysbacteriosis mediated mucosal immunity in IgA nephropathy

“…Uriol-Rivera et al [ 198 ] first implemented an innovative combination therapy in seven patients with refractory IgAN, initiating treatment with the anti-inflammatory agent paricalcitol followed by IL-17 A blockade using secukinumab. Paricalcitol is a selective vitamin D receptor agonist that inhibits the differentiation of Th1 and Th17 cells and promotes the generation of Tregs, thereby suppressing excessive immune responses and inflammation.…”