- Design
- Phase 3 RCT
- Population
- 142 adults with primary membranous nephropathy
- Primary outcome
- Complete remission at week 104
- Effect
- 37% vs 6%; difference 31 points (95% CI 18 to 44)
MAJESTY was a phase 3 trial that randomised 142 adults with primary membranous nephropathy to intravenous obinutuzumab, a type II anti-CD20 antibody, or oral tacrolimus. It was funded by the manufacturer and published in NEJM on 5 June 2026; it reaches this desk now through a later harvest.
Complete remission (protein-to-creatinine ratio 0.3 or less with stable eGFR) at 104 weeks occurred in 37% with obinutuzumab and 6% with tacrolimus (adjusted difference 31 percentage points, 95% CI 18 to 44). Complete or partial remission at 104 weeks and complete remission at 76 weeks also favoured obinutuzumab. Sustained eGFR decline of 30% or more did not differ, so later end points were not formally tested. Grade 3 or worse adverse events were 22% versus 19%, and serious infections 3 versus 4 per 100 patient-years.
Tacrolimus often induces remission that relapses on withdrawal; obinutuzumab produced far more complete, durable remissions at two years. This supports anti-CD20 therapy as first-line immunosuppression over calcineurin inhibitor monotherapy. Cost and access, including in India, will determine whether obinutuzumab or the cheaper rituximab is used.
- Prefer anti-CD20 therapy over tacrolimus monotherapy for primary membranous nephropathy needing immunosuppression.
- Monitor anti-PLA2R titres to judge response.
- Screen for hepatitis B before anti-CD20 therapy.
- Watch for infusion reactions and neutropenia.
Why it matters
Complete remission, not just proteinuria reduction, is what protects kidney function long term.
Don't overread it
The trial compared obinutuzumab with tacrolimus, not with rituximab, and showed no difference in eGFR decline at two years.
The statistics, in plain English
A 31-point difference with an interval from 18 to 44 is large and clearly beyond chance. The trial did not show a difference in eGFR decline over two years, which is expected in a slowly progressive disease but means the kidney-survival benefit is inferred, not shown. Rituximab was not the comparator.
Read the rest in the app
You have read your two free briefings this month. The app carries all 27 specialties, every morning, free — and this finding is waiting in it.
Scan to keep reading on your phone. No account needed to start.
Tomorrow morning, before your first patient
One edition a day for nephrology, written by the desk, every claim tied to its paper. Six minutes.
Get the app — free