What are the considerations for using Krystexxa (pegloticase) in patients undergoing hemodialysis?

Krystexxa (Pegloticase) in Hemodialysis Patients

Krystexxa can be safely administered to patients undergoing hemodialysis without dose adjustment, as hemodialysis does not significantly affect pegloticase serum concentrations or its uric acid-lowering efficacy. 1

Pharmacokinetic Profile in Hemodialysis

The pharmacokinetics of pegloticase are unaffected by hemodialysis:

• Serum pegloticase concentrations remain stable during and after dialysis sessions, with no significant removal of the drug by hemodialysis 1
• A single 8 mg intravenous dose administered 3 hours prior to hemodialysis maintained stable serum concentrations throughout the dialysis procedure 1
• The large molecular size of pegylated uricase prevents its removal through dialysis membranes 1

Pharmacodynamic Efficacy

Pegloticase maintains full therapeutic efficacy in dialysis patients:

• Serum uric acid levels fall to undetectable levels within 3 hours of administration and remain suppressed for up to 72 hours post-dose 1
• The uric acid-lowering capacity is preserved regardless of dialysis timing 1
• Phase 3 trial data demonstrate that pegloticase efficacy is independent of chronic kidney disease stages 1-4, and this extends to stage 5 disease requiring hemodialysis 1

Dosing Recommendations

Standard dosing of 8 mg intravenously every 2 weeks should be used without modification in hemodialysis patients. 1

• No dose adjustment is required based on renal function or dialysis schedule 1
• Unlike many other medications used in dialysis patients that require dose reduction or timing adjustments 2, pegloticase does not follow this pattern 1
• The drug can be administered at any time relative to the dialysis session, as dialysis does not remove pegloticase from circulation 1

Safety Considerations

The safety profile in hemodialysis patients mirrors that of the general refractory gout population:

• Infusion reactions occur in 26-31% of patients and represent the primary safety concern 3
• Gout flares are common (77% of patients) during initial treatment 3
• Approximately 90% of patients develop anti-pegloticase antibodies, which can lead to loss of therapeutic response 4
• Antibody formation is associated with both increased infusion reaction risk and diminished efficacy 3, 5
• No new safety signals were detected specifically in the hemodialysis population 1

Clinical Management Strategy

Implement prophylactic anti-inflammatory therapy to prevent gout flares and potentially reduce antibody formation:

• Glucocorticosteroids should be used as prophylaxis during pegloticase therapy 3
• This strategy may help prevent both gout flares and antibody-mediated loss of efficacy 3
• Monitor for infusion reactions during each administration 3, 5

Monitoring Requirements

Track serum uric acid levels to identify treatment responders versus non-responders:

• Target serum uric acid level is <6 mg/dL (0.36 mmol/L) 3
• Approximately 58% of patients are non-responders by this definition 3
• Loss of uric acid-lowering effect during months 3-6 occurs in 80% of patients, likely due to antibody formation 3
• Monitor for clinical improvement in tophi size, which occurs in approximately 40% of responders 3

Important Caveats

• Pegloticase does not reduce estimated glomerular filtration rate in CKD patients, making it safe from a nephrotoxicity standpoint 1
• The high rate of antibody formation and subsequent loss of efficacy limits long-term utility in many patients 3, 4
• Consider pegloticase as a bridging therapy for tophi clearance in severe chronic refractory gout rather than indefinite maintenance therapy 3
• Hemodialysis patients already face substantial medication burden (averaging 10 prescription medications) and high rates of drug-related problems 6, so careful integration of pegloticase into the existing regimen is essential