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Efficacy of rituximab versus tacrolimus in difficult-to-treat steroid-sensitive nephrotic syndrome: an open-label pilot randomized controlled trial.

ABSTRACT: Rituximab and tacrolimus are therapies reserved for patients with frequently relapsing or steroid-dependent nephrotic syndrome who have failed conventional steroid-sparing agents. Given their toxicities, demonstrating non-inferiority of rituximab to tacrolimus may enable choice between these medications. This investigator-initiated, single-center, open-label, pilot randomized controlled trial examined the non-inferiority of two doses of intravenous (IV) rituximab given one-week apart to oral therapy with tacrolimus (1:1 allocation), in maintaining sustained remission over 12 months follow-up, in patients with difficult-to-treat steroid-sensitive nephrotic syndrome, defined as frequently relapsing or steroid-dependent disease that had failed ≥ 2 steroid-sparing strategies. Secondary outcomes included frequency of relapses, proportion with frequent relapses, time to relapse and frequent relapses, and adverse events (CTRI/2018/11/016342). Baseline characteristics were comparable for 41 patients randomized to receive rituximab (n = 21) or tacrolimus (n = 20). While 55% of patients in each limb were in sustained remission at 1 year, non-inferiority of rituximab to tacrolimus was not demonstrated (mean difference 0%; 95% CI - 30.8%, 30.8%; non-inferiority limit - 20%; P = 0.50). Frequent relapses were more common in patients administered rituximab compared to tacrolimus (risk difference 30%, 95% CI 7.0, 53.0, P = 0.023). Both groups showed similar reductions in relapse rates and prednisolone use. Common adverse events were infusion-related with rituximab and gastrointestinal symptoms with tacrolimus. Therapy with rituximab was not shown to be non-inferior to 12-months treatment with tacrolimus in maintaining remission in patients with difficult-to-treat steroid-sensitive nephrotic syndrome. Frequent relapses were more common with rituximab. While effective, both agents require close monitoring for adverse events. A higher resolution version of the Graphical abstract is available as Supplementary information.

SUBMITTER: Mathew G

PROVIDER: S-EPMC8919684 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe anti-CD20 monoclonal antibody rituximab (RTX) has been proposed as a rescue therapy for difficult-to-treat nephrotic syndrome (NS). We conducted a clinical trial to evaluate the efficacy and safety of RTX in children with difficult-to-treat NS dependent on or resistant to steroids and calcineurin inhibitors (CNIs).MethodsA multicenter open-label trial was performed at 8 major pediatric nephrology centers in Korea. The investigation consisted of a randomized controlled trial for steroid- and CNI-dependent NS (DDNS; randomization into the RTX group and the control group, at a ratio of 2:1) and a single-arm study of steroid and CNI-resistant NS (DRNS). DDNS patients in the RTX group and DRNS patients received a single dose of intravenous RTX (375 mg/m of body surface area) for B-cell depletion. A second RTX dose was administered at week 2 if the first dose failed to achieve depletion of CD19(+) cells. The primary endpoint was rate of maintaining remission at 6 months after treatment for DDNS and rate of remission achievement for DRNS.ResultsSixty-one children with DDNS were enrolled while in remission and randomized to the control group (21 patients) or the RTX group (40 patients). At 6 months after treatment, the remission rates were 74.3% in the RTX group and 31.3% in the control group (P = .003). The mean duration of remission maintenance was significantly higher in the RTX group than in the control group (9.0 vs 2.9 months, P = .004). Of the 23 patients with DRNS enrolled in the single-arm study and treated with RTX, 9 (39.1%) achieved partial or complete remission within 6 months. Depletion of B cells occurred in all patients with RTX therapy. Thirty patients (50.8% of 59 patients analyzed) experienced mild and transient infusion reaction during RTX administration, and most adverse events were mild.ConclusionsRTX administration was safe and effective in patients with difficult-to-treat NS. One or 2 doses of RTX may be sufficient to deplete B cells and achieve better control of pediatric NS.

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Efficacy of rituximab versus tacrolimus in difficult-to-treat steroid-sensitive nephrotic syndrome: an open-label pilot randomized controlled trial.

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