Abstract: TH-PO132

Role of Rituximab in Primary Membranous Nephropathy Refractory to Modified Ponticelli/Calcineurin Based Treatment

Session Information

Category: Glomerular

  • 1005 Clinical Glomerular Disorders

Authors

  • Sethi, Jasmine, Post Graduate Institute of Medical Education and Research (PGIMER), CHANDIGARH, Haryana, India
  • Kohli, Harbir Singh, Post Graduate Institute of Medical Education and Research (PGIMER), CHANDIGARH, Haryana, India
  • Ramachandran, Raja, Post Graduate Institute of Medical Education and Research (PGIMER), CHANDIGARH, Haryana, India
Background

Rituximab is emerging as a promising therapeutic agent particularly in the management of refractory primary membranous nephropathy. What should be dosage schedule to avoid toxicity without compromising the efficacy is a matter of concern and data to this regard is limited. This is a single center prospective study to evaluate the role of B cell titrated protocol of rituximab in adults with PMN who failed treatment with conventional immunosuppressive agents and its possible association with aPLA2R antibodies.

Methods

14 patients aged 14-65 years of refractory PMN were given intravenous rituximab at a dose of 375mg/m2 in a tertiary center in northern India. Following rituximab injection, CD19 counts were monitored weekly for 4 weeks followed by monthly for 6 months. If CD19 count was >5/µL (or >1%), repeat doses of rituximab were given. The change in laboratory parameters (24 urinary protein, serum albumin and serum creatinine) were recorded at the baseline, and monthly till 6 months after rituximab administration. Serum sample drawn just before rituximab infusion and at the end of 6th month post-infusion were tested for aPLA2R by ELISA

Results

At the end of 6 months, 6 out of 14 patients (42.8%) responded, with 1/14 (7.1%) achieving CR and 5/14 (35.7%) achieving PR. Eight out of 14 (57.1%) patients showed no response to rituximab at the end of the 6 months. Mean proteinuria decreased from 4.6 ±1.7 g/day at baseline to 3.3 ±2.1 g/day at 3 months, and 3.2 ±2.3 g/day at 6 months (p=0.29). Mean serum albumin also increased from 2.4 ±0.6 g/dl at baseline to 2.8 ±0.6 g/dl at 3 months, and 3.2 ±0.6 g/dl at 6 months. (p=0.002). Average time to CD19 reconstitution was 3.1± 0.8 (2-4) months. Rituximab dose administered during 6 month period was 1289±720 (600-2800) mg. aPLA2R antibody testing was done in 13 patients. Among these, all 13 patients presented with high levels of antibodies before the treatment, eight of them experienced a reduction of aPLA2R antibody titer, while 5 patients experienced no change after treatment (all five patients continued to have resistant disease).

Conclusion

CD19 titrated rituximab therapy is effective in achieving remission in 42.85% of patients of PMN refractory to prior immunosuppression. Titrated therapy might enhance the safety without compromising the efficacy of the therapy.