TOCILIZUMAB – A HOPE FOR CHRONIC ANTIBODY MEDIATED REJECTION

Introduction:

Long term transplant outcomes remain dismal and, particularly, in low-risk populations like living donor recipients, there has been no improvement in last 2 decades. Chronic antibody mediated rejection (cAMR), the most important contributory cause has few effective treatment options. One emerging option is Tocilizumab, IL-6 receptor inhibitor, for modulation of inflammation and humoral immunity. Its benefits are mediated by stabilizing graft function, reducing dn-DSA load, decreasing anti-HLA IgG (total) and IgG3 load and improving renal transplant histology pre vs post intervention. We had intervention with Tocilizumab (Intervention TCZ arm, prospective cohort) on top of current standard of care therapy i.e. IVIg +/- Rituxmab +/- Plasmapheresis (SOC, historical cohort) and looked for any additional benefit in TCZ arm.

Methods:

We identified 30 patients diagnosed with cAMR from 2017 to June 2022 in IPGMER, Kolkata or elsewhere who received treatment with us. All received IVIG at dose 2gm/kg and rituximab with or without plasmapheresis. Tocilizumab intervention was given in 10 patients who gave consent with dose of 8 mg/kg single dose every month for next 2 years, with prior negative screening for infections. Most patients were low risk living donor transplants and received IL-2 Blocker( high risk: 4/10 in TCZ group and 16/20 in SOC arm, received Anti Thymocyte Globulin (ATG) induction). All patients were on standard 3 drug immunosuppression with appropriate Tacrolimus target levels. We could not frequently measure de novo – donor specific antibodies (outsourced). Standard chronic kidney disease (CKD) retardation regime was followed for all. For outcomes, we measured for percentage proteinuria improvement ( surrogate marker of renal progression, cardiovascular (CV) mortality) and mean change of serum creatinine ( graft function stabilization) along with graft and patient survival in both arms.

Results:

Median age of the recipients, gender distribution, induction and maintenance immunosuppression were not different in SOC and TCZ arm. In SOC arm, during 18 months of follow up, 13/20 patients were HD free, 7 patients died ( 4 due to infections and 3 due to CV mortality). With optimized CKD retardation, mean graft and patient survival were 21 months and 27.7 months, respectively, in the TCZ arm and 30.2 months and 37.2 months, respectively, in SOC arm. In TCZ group, 3 patients were initiated on HD, but rest are HD free and there was no infection related death. At 18 months, the mean 24 hour urinary protein in TCZ arm was 1082.57 +/- 173.78 mg/day and in SOC arm it was 2554.75 +/- 889.93 mg/day (p value < 0.001), thus, suggesting a significant reduction in proteinuria in TCZ arm(shown graphically in Figure 1). At the end of the study period of 18 months, though there was a fall in mean eGFR in both the arms, being 39.14 +/- 10.99 ml/min/1.73 m2 in TCZ arm and 19.5 +/- 10.35 ml/min/1.73 m2 in SOC arm, there was a significant comparative decline in SOC compared to TCZ arm (p value 0.003)((shown graphically in Figure 2)).   

Conclusions:

Tocilizumab may stabilize graft function better on top of standard of care therapy. The proteinuria reduction may be explained by reduction of inflammation in IFTA region and confirmation needs a repeat biopsy at end of 2 years.

I have no potential conflict of interest to disclose.

I did not use generative AI and AI-assisted technologies in the writing process.