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Subcutaneous C1 esterase inhibitor dosing in obese patients

Question:

2/27/2018
We have an obese patient with HAE with BMI 34. Is there any dose recommendation of Haegarda for prophylaxis HAE in obese patients? Do we need to use an ideal body weight?

Answer:

There is evidence of dose effect with replacement C1 esterase inhibitor, although the intravenous product approved for prevention is not dosed based upon weight. However, a study showed that breakthrough angioedema occurred with twice weekly replacement and these episodes correlated to the end of the dosing interval (1). Subcutaneous administration was pursued for various reasons, but one was to reduce the greater peak to trough ratios seen with the IV formulation. Pharmacokinetic profile showed that weight based subcutaneous dosing provided favorable outcomes (1). The efficacy of weight based preventative therapy has been confirmed with 40 IU/kg providing significant clinical benefit, although 60 IU/kg had a greater effect (median attack rate reduction of 89% with 40 IU/kg and 95% with 60 IU/kg] (2,3). Weight based dosing is required to achieve the targeted plasma level of at least 30% and ideally 40-50% of normal level of C1 esterase inhibitor activity, a level associated with clinical improvement (3). All of these studies are based upon total body weight, not ideal body weight.

In summary, the dose of purified, subcutaneous C1 esterase inhibitor is based upon pharmacokinetic and pharmacodynamic profiles and achieving an C1 esterase inhibitor activity level of 40-50% of normal. Dosing is based upon total body weight. Thus, obese patients require a greater dose to achieve sufficient blood C1 esterase inhibitor activity and dosing is based upon total body weight, not ideal body weight.

1. Aygören-Pürsün E, Martinez-Saguer I, Longhurst HJ, et al. C1 inhibitor for routine prophylaxis in patients with hereditary angioedema: interim results from a European Registry study. J Allergy Clin Immunol 2016;137:AB251-AB251. abstract.
2. Zuraw BL, Cicardi M, Longhurst HJ, et al. Phase II study results of a replacement therapy for hereditary angioedema with subcutaneous C1-inhibitor concentrate. Allergy 2015;70:1319-1328
3. Longhurst H, Cicardi M, Craig T et al. Prevention of hereditary angioedema attacks with subcutaneous C1 inhibitor. N Engl J Med 2017;376:1131-40.

I hope this information is of help to you and your practice.

All my best.
Dennis K. Ledford, MD, FAAAAI