Table 2:

Challenges in imlifidase use and potential solutions

Challenge	Impact on treatment	Possible solutions
Cleavage of IgG antibodies by imlifidase	Potential interference with the effectiveness of other IgG-based desensitizing agents	Suggested dosing intervals after imlifidase; rATG = 1 week, equine ATG = no need, alemtuzumab, adalimumab, basiliximab, denosumab, etanercept, rituximab = 4 days, IVIG = 12 hours
Infusion-related reactions, including allergic reactions	Reluctance to continue imlifidase treatment due to possible anaphylaxis	Thorough monitoring of patient vital signs and cessation of infusion temporarily or permanently depending on the relevancy to imlifidase
Infections of any origin, including chronic infections	Risk of complications or worsening of infections	Ensure comprehensive infection control before initiating imlifidase
	Need for prophylactic antibiotics	No uniform consensus on the choice of prophylactic antibiotics
Temporary reduction in vaccine protection	Concerns about vulnerability to infections during this period	Educate patients on the temporary reduction in vaccine protection. Continue to monitor antibody titres for vaccines
Influence of anti-imlifidase antibodies on efficacy	Impact on the efficacy of a second imlifidase dose	Avoid re-administration after 24–96 hours. Maintain immunosuppression with alternative agents
Contraindications (hypersensitivity, ongoing infection, TTP)	Inability to use imlifidase due to contraindications	Explore alternative treatment options for patients with contraindications
Adverse reactions in clinical studies (infusion site reactions, liver enzyme elevations, muscle pain, anaemia, headaches, and flushing)	Discomfort from potential side effects	Communicate potential side effects compared with potential benefits
	Risk of discontinuation due to adverse reactions	Schedule regular visits and plan symptomatic treatment for specific side effects

rATG: rabbit anti-thymocyte globulin; TTP: thrombotic thrombocytopenia purpura.