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Abstract: FR-PO0847

Cancer Risk Associated with Immunosuppressive Therapy in Glomerular Diseases: A Population-Based Cohort Study

Session Information

Category: Glomerular Diseases

  • 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

  • Han, Jialin, The University of British Columbia Faculty of Medicine, Vancouver, British Columbia, Canada
  • Zhao, Yinshan, The University of British Columbia Faculty of Medicine, Vancouver, British Columbia, Canada
  • Canney, Mark, University of Ottawa, Ottawa, Ontario, Canada
  • Atiquzzaman, Mohammad, The University of British Columbia Faculty of Medicine, Vancouver, British Columbia, Canada
  • Levin, Adeera, The University of British Columbia Faculty of Medicine, Vancouver, British Columbia, Canada
  • Barbour, Sean, The University of British Columbia Faculty of Medicine, Vancouver, British Columbia, Canada
Background

Patients with glomerular disease (GN) are at an increased risk of cancer. However, the contribution of immunosuppression to this risk remains unclear

Methods

We conducted a population-level analysis of adults with biopsy-proven GN in British Columbia, Canada, from 2000 to 2020. Antimetabolites and calcineurin inhibitors were quantified using defined daily dose [DDD]. Weighted cumulative exposure [WCE] was used to determine the most appropriate measure of each immunosuppression exposure associated with cancer risk, which was then evaluated using an extended Cox regression model.

Results

The cohort included 4039 patients with IgA nephropathy (N=1200), membranous nephropathy (N=542), focal segmental glomerulosclerosis (N=770), minimal changed disease (N=364), lupus nephritis (N=528) and ANCA glomerulonephritis (N=602). Over a median follow-up of 7.8 years, 384 (9.5%) patients developed cancer. WCE models indicated that use of antimetabolites in the preceding four years had a significant impact on cancer risk, but calcineurin inhibitors was not (Figure 1). In fully adjusted survival model, cumulative exposure to antimetabolites showed a dose-dependent relationship with cancer risk. Moderate exposure (1100–1300 DDD over four years) was associated with an intermediate risk (hazard ratio [HR] 1.11, 95% confidence interval [CI] 0.35–3.58), while high exposure (≥1300 DDD over four years) was linked to a nearly four-fold increase of hazard (HR 3.83, 95% CI 1.98–7.44) (Table 1).

Conclusion

Antimetabolites but not calcineurin inhibitors are associated with an increased risk of cancer in patients with GN. This indicates need for personalized immunosuppressive strategies that carefully balance disease control with long-term safety. Future work will explore the cancer risk associated with other immunosuppression medications.

Digital Object Identifier (DOI)