Adrenal insufficiency is a contraindication for omalizumab therapy in mast cell activation disease: risk for serum sickness

Abstract

Omalizumab is an effective therapeutic humanized murine IgE antibody in many cases of primary systemic mast cell activation disease (MCAD). The present study should enable the clinician to recognize when treatment of MCAD with omalizumab is contraindicated because of the potential risk of severe serum sickness and to report our successful therapeutic strategy for such adverse event (AE). Our clinical observations, a review of the literature including the event reports in the FDA AE Reporting System, the European Medicines Agency Eudra-Vigilance databases (preferred search terms: omalizumab, Xolair®, and serum sickness) and information from the manufacturer’s Novartis database were used. Omalizumab therapy may be more likely to cause serum sickness than previously thought. In patients with regular adrenal function, serum sickness can occur after 3 to 10 days which resolves after the antigen and circulating immune complexes are cleared. If the symptoms do not resolve within a week, injection of 20 to 40 mg of prednisolone on two consecutive days could be given. However, in MCAD patients whose adrenal cortical function is completely suppressed by exogenous glucocorticoid therapy, there is a high risk that serum sickness will be masked by the MCAD and evolve in a severe form with pronounced damage of organs and tissues, potentially leading to death. Therefore, before the application of the first omalizumab dose, it is important to ensure that the function of the adrenal cortex is not significantly limited so that any occurring type III allergy can be self-limiting.

Omalizumab in severe asthma and food allergies with IgE levels >1500 kU/L: Two‐year evaluation

“…These immune complexes can deposit in various tissues, potentially causing inflammation and tissue damage, especially in organs such as the kidneys, and induce serum sickness, a delayed hypersensitivity reaction. 2,3 For patients with high tIgE, we regularly performed IgE immunoapheresis introductory to omalizumab treatment until September 2019. 4,5 However, postmarketing observational studies suggested that omalizumab efficacy is conserved also in asthmatic patients with tIgE >1500 UI/L without any significant side effect.…”

“…One area of concern when using omalizumab is its potential impact on circulating immune complexes and renal function. 2,3 Serum sickness has been reported following treatment with omalizumab in the context of mast cell activation disease (MCAD). 3 Studies evaluating renal function in patients receiving omalizumab with initial tIgE<1500 kUI/L shown no significant effects on renal parameters, including serum creatinine levels and glomerular filtration rate.…”

“…2,3 Serum sickness has been reported following treatment with omalizumab in the context of mast cell activation disease (MCAD). 3 Studies evaluating renal function in patients receiving omalizumab with initial tIgE<1500 kUI/L shown no significant effects on renal parameters, including serum creatinine levels and glomerular filtration rate. In our cohort, the values of plasma creatinine analyzed showed a nearly constant value during the 2-year-long follow-up.…”