Kidney Compass: Rituximab Cuts Relapse Risk in MCD, FSGS in TURING Trial

At the European Renal Association (ERA) Congress in Glasgow, Scotland, results from the TURING trial offered long-awaited evidence that rituximab can meaningfully reduce relapse rates in adults with minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS).

These conditions have been historically managed with prolonged, high-dose corticosteroid courses, carrying a substantial burden of adverse effects. In this episode of Kidney Compass, host Brendon Neuen, MBBS, PhD, spoke with Lisa Willcocks, MBBChir, MRCP, PhD, a consultant nephrologist who leads the primary glomerular disease service at Addenbrooke's Hospital in Cambridge, United Kingdom, about the trial she presented as a late-breaking clinical result at the congress.

"Rituximab is now so much cheaper than it used to be," Willcocks said. "Hopefully, this is a drug that will be available to people worldwide and will spare the burden of steroids that patients have been exposed to."

Why Rituximab Was Evaluated in Adult Nephrotic Syndrome

The rationale for the TURING trial stems from a well-recognized clinical challenge: although most adults with MCD and FSGS respond initially to corticosteroids, the majority will relapse. Standard of care, as outlined by KDIGO guidelines, calls for prednisolone at 1 mg/kg per day, capped at 80 mg, followed by a slow taper over six months. In patients who relapse, this cycle repeats, meaning individuals with frequently relapsing disease accumulate substantial cumulative steroid exposure over years, often beginning in early adulthood.

Turing Trial Design: Population, Randomization, and Steroid Weaning Stratification

The TURING trial randomized 149 adults in a 1:1 ratio to either rituximab or placebo. Rituximab was administered as two 1 g doses given 1 to 3 weeks apart, initiated within 4 weeks of starting corticosteroid treatment for nephrotic syndrome. Patients who remained in remission at 6 months received a third dose of their assigned treatment. In the placebo arm, participants who relapsed were unblinded and offered open-label rituximab, providing an additional dataset on delayed treatment initiation.

The trial population had a median age in the early 50s, with approximately 70% identifying as White British, reflective of the UK referral base. 38% of participants had FSGS, while the remainder had MCD. Additionally, approximately one-third had de novo disease and two-thirds had relapsing disease at enrollment.

An important design feature was stratification by steroid tapering regimen. Clinicians were permitted to choose either the standard KDIGO taper or a faster wean, the latter reducing total prednisolone exposure by approximately 1 gram, allowing the trial to assess whether the rituximab effect held regardless of steroid management strategy.

What the Phase 3 Trial Showed: Relapse Rates, Disease Subgroups, and Duration of Remission

The primary endpoint was time from remission to relapse, assessed over a median follow-up of 2.8 years, with some participants followed for up to 4 to 5 years. In the placebo group, the median time to relapse was under 6 months. In the rituximab group, the median time to relapse was not reached during the follow-up period, meaning more than half of treated patients remained in remission at study close. Overall, rituximab was associated with a greater than 50% reduction in relapse rate compared with placebo.

Willcocks reported consistent effects across MCD and FSGS subgroups. In patients with relapsing disease, results were statistically significant; in those with de novo disease, the odds ratios were similar in direction and magnitude, but the confidence interval crossed zero, likely reflecting the smaller sample size in that stratum, approximately 50% of de novo placebo patients relapsed compared with approximately 22% in the de novo rituximab group. Notably, the benefit of rituximab was preserved regardless of which steroid tapering schedule was used, supporting the possibility that a faster, less toxic steroid wean can be combined with rituximab without compromising efficacy.

In the open-label phase, patients from the placebo arm who subsequently received rituximab after relapse showed Kaplan-Meier curves nearly identical to those of the primary rituximab group, underscoring the consistency and reproducibility of the effect.

Safety Findings Reported With Rituximab in the Turing Trial

Adverse event rates were similar between the rituximab and placebo groups, and no new safety signals emerged in the open-label treatment phase. Wilcox noted that although participants frequently entered the trial with hypogammaglobulinemia secondary to nephrotic syndrome, IgG levels improved as patients achieved remission, and no cases of treatment-emergent hypogammaglobulinemia were identified during the trial period. B-cell monitoring via CD19 levels was not performed systematically, partly to preserve blinding and partly because existing literature suggests limited utility in predicting relapse timing.

Unanswered Questions: Redosing Timing, Biomarkers, and Long-Term Use

Several clinically relevant questions remain open following the Turing trial. Willcocks acknowledged that the trial did not establish an optimal redosing interval for rituximab in patients who achieve sustained remission. Based on her clinical experience following the trial, she described a general approach of administering 2 initial doses followed by a 6-month dose and then monitoring for relapse, noting that most patients in the trial remained in remission for approximately two to three years from the time of initial treatment. Whether an annual maintenance dose would be sufficient to sustain remission for a broader population, and how to individualize that decision, were flagged as priorities for future investigation.

The role of anti-nephrin antibodies, a biomarker not yet available when the trial was designed, was also identified as an emerging area of interest, with Wilcox suggesting it may eventually inform relapse prediction. The trial's investigator-initiated design limited some ancillary biomarker collection, though a large dataset has been assembled, and the investigators indicated openness to collaborative analyses.

Editor’s Note: Willcocks reports relevant disclosures with Chemocentryx, Rigel, Novartis, GSK, and others.

References

1. Willcocks L. TURING trial: rituximab in adults with minimal change disease and FSGS. Presented at: European Renal Association Congress; Glasgow, Scotland; 2025.

2. Kidney Disease: Improving Global Outcomes (KDIGO) Glomerular Diseases Work Group. KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases. Kidney Int. 2021;100(4S):S1-S276.

3. Ravani P, Magnasco A, Edefonti A, et al. Short-term effects of rituximab in children with steroid- and calcineurin-dependent nephrotic syndrome: a randomized controlled trial. Clin J Am Soc Nephrol. 2011;6(6):1308-1315. doi:10.2215/CJN.09421010

4. Rovin BH, Adler SG, Barratt J, et al. Executive summary of the KDIGO 2021 Guideline for the Management of Glomerular Diseases. Kidney Int. 2021;100(4):753-779.