Guselkumab and other humanized monoclonal antibody skin testing
Question:
3/11/2020
I have a 60 year-old female who was put on Tremfya for her psoriasis. After few injections she developed a localized hives at the site of the injection. My questions are: Is a skin test a valid way and at what concentration? What is her risk of systemic reaction? What is the practical way to address this issue: premeditates her or splitting the dose?
Answer:
Guselkumab, and all other monoclonal antibodies can induce IgE-mediated hypersensitivity. With continued exposure, anaphylaxis would be very unlikely, given the long half-life of humanized monoclonal antibodies, though hives may continue to occur at the site of administration. If there is more than five half-lives (> 100 days) between administrations, then the risk for anaphylaxis with systemic exposure would be much higher if IgE-mediated hypersensitivity exists. These individuals should be desensitized prior to readministration. Immediate -type hypersensitivity intradermal skin testing with monoclonal antibodies, or any other therapeutic protein, can typically be safely done using 0.02 mL of a 1:1000 dilution of the 100 mg/ml stock solution (0.1 mg/ml), followed by 1:100 (1 mg/ml) and 1:10 (10 mg/ml) dilutions if the previous results were negative. Read at 15 minutes and a positive test would be a wheal > 5 mm with flare > wheal. Premedication with cetirizine 10 to 20 mg 1/2 hour prior to administration might be helpful in reducing local hives. Dose splitting will probably not have much of an impact on local symptoms.
https://www.jacionline.org/article/S0091-6749(18)30306-3/pdf
Eric Macy, MD, MS, FAAAAI