Comparative Efficacy and Safety of Low-Dose versus Standard-Dose Rituximab in Patients with Primary Membranous Nephropathy: An Open-Label Randomized Controlled Trial

After getting all necessary clearances, patients will be enrolled in the study as per the inclusion and exclusion criteria. Patients will be randomized using block randomization (with block size of four using Microsoft Excel 2021) into two groups study group and standard arm group. Study group will be receiving low dose monthly rituximab therapy (100mg IV Rituximab) whereas control group would receive standard dose therapy with 1gm Rituximab 2 weeks apart.

All patients will be screened for HIV/HBV/HCV AND KOCH before enrolling in the study. 6 months INH prophylaxis will be given for latent tuberculosis patients prior to treatment with rituximab.

Complete and partial remission to be defined as per KDIGO guidelines.

Patients in study group will be given 100mg iv Rituximab for 3 consecutive months and assessed for complete or partial remission and trends of anti-PLA2R antibody levels.

Patients who attained complete remission or anti-PLA2R antibody titres negative at 3 months will be followed up with conservative therapy upto 12 months.

Patients who achieved partial remission or no remission or persistent positive anti-PLA2R antibody titres at end of 3 months will be further continued monthly (100mg iv Rituximab) dose for further 3 months

Patients who achieved complete remission or anti-PLA2R antibody titres negative at 6 months will be followed up with conservative therapy upto 12 months (from the start of therapy).

Patients who achieved partial remission or decrease in anti-PLA2R antibody titres at end of 6 months will be further given 3 months 100mg Rituximab therapy.

Patients who did not achieve complete remission at end of 6 months will be defined as treatment failure and converted to standard dose of therapy or alternate therapy.

Patients who achieved partial remission or anti-PLA2R antibody titres negative at 6 months will be followed up with conservative therapy for next 12 months (from the start of therapy).

Response rates will be assessed at 3,6, 9 and 12 months. Patient will be monitored 3,6,9 and 12 monthly with CD19/20 levels. CD19/20 levels will be monitored 3 monthly until target levels reached (<1% or < 5cells).

All patients will be undergoing 3 monthly assessments for proteinuria (Complete urine examination/Urine spot PCR/S. total protein/S.albumin/24 hours UP) and renal function (s. creat and urea levels).

Anti-PLA2R antibody levels will be done at baseline,3,6, and 9months and trends will be analyzed.

 Patients not achieving complete and partial remission will be termed as non-responders. Relapse will be defined as recurrence of proteinuria >3.5gm after achieving complete and partial remission.

 Conservative therapy will also be given simultaneously to patients, ACE/ARBs at maximum tolerable doses.

The primary outcome is the remission rate (complete remission + partial remission) at end of three, six, nine and twelve months.

The changes in Anti-PLA2R levels at end of three, six, nine and twelve months, changes in proteinuria levels, changes in eGFR at end of three, six, nine and twelve months will also be considered in primary outcomes.

Infections requiring hospitalization, serious allergic reactions, malignancies, development of Koch or any severe septicemia will be considered as serious side effects and assessed.