Antibody-mediated rejection-treatment standard

Area of Science:

• Transplantation immunology
• Nephrology
• Graft survival research

Background:

• Antibody-mediated rejection (AMR) is a primary driver of graft failure, imposing substantial clinical and economic burdens.
• Despite decades of recognition, AMR treatment lacks standardization and regulatory-approved therapies.
• Existing evidence for AMR treatments is limited, with many trials yielding negative results.

Purpose of the Study:

• To critically re-evaluate the current evidence base for antibody-mediated rejection treatment strategies.
• To inform clinical decision-making in the absence of robust, approved AMR therapies.
• To identify promising therapeutic targets and approaches for future AMR treatment development.

Main Methods:

• Systematic review and critical appraisal of existing clinical trial data for AMR treatments.
• Analysis of expert consensus recommendations and their evidentiary basis.
• Evaluation of emerging therapeutic strategies targeting AMR pathobiology.

Main Results:

• Current evidence for steroids, rituximab, bortezomib, and IL-6 antagonists in AMR treatment is insufficient.
• Immunoadsorption and potentially high-dose IVIG are considered for early AMR, with limited supporting data.
• Emerging CD38 antibodies demonstrate potential by targeting endothelial inflammation, and complement inhibition is an option for severe early AMR.

Conclusions:

• Robust evidence supporting common AMR treatments is lacking, necessitating a re-evaluation of clinical practice.
• Novel therapies targeting cellular inflammation (e.g., CD38 antibodies) and complement pathways offer future hope.
• Ongoing clinical trials for agents like efgartigimod, tocilizumab, and felzartamab may lead to approved, effective AMR treatments.