Serum free IgE guided dose reduction of omalizumab: a case report
© The Author(s) 2017
Received: 6 May 2017
Accepted: 4 August 2017
Published: 31 August 2017
Omalizumab is a human IgG1 antibody against IgE used as a therapy for sever asthmatic patients with asthma. According to the guidelines of the Global Initiative for Asthma, omalizumab is an add-on drug at treatment step 5 that is used for severe asthma patients who are allergic to perennial allergens. The effects of omalizumab for severe asthma therapy have been validated in multiple clinical studies. However, the long-term effects of omalizumab on IgE production and possibility of resetting of administration dose of omalizumab remain unknown.
The serum total and free IgE levels were measured over time in a 63-year-old female patient with allergic asthma who was administered 375 mg omalizumab biweekly for 36 months. Her symptoms did not worsen and clinical course remained favorable after reducing the dose to 375 mg per month. The serum free IgE levels temporarily increased following a dose reduction of omalizumab. The serum free IgE trough level temporarily increased at 4 weeks after capable to reduce the dosage; however, thereafter, the serum free IgE level decreased to desired levels (below 30 ng/mL).
The present case shows the possibility of reducing the dose following the long-term use of omalizumab. Considering the high medical cost of omalizumab, the dose reduction may be a viable option. It may be useful to measure the serum free IgE level to appropriately identify patients in whom the dose can be reduced, and to carefully monitor the clinical course.
To the editor
Omalizumab is a human IgG1 antibody against IgE used to treat patients with severe allergic asthma with symptoms that are poorly controlled with high doses of inhaled steroids. Numerous clinical studies have demonstrated the effectiveness of omalizumab therapy on intractable atopic asthma, and this has become one of the few available treatment modalities. The goal of omalizumab therapy is to achieve free IgE (unbound IgE that can bind to IgE receptors) of ≤25 ng/mL ; however, it is impossible to distinguish between free IgE and IgE-omalizumab complexes using conventional measurements of serum total IgE. Conventionally, the serum free IgE levels could not be assessed after administering omalizumab .
To overcome this issue, we previously developed ELISA with solid-phase soluble FcεRI to allow for the measurement of serum free IgE levels in patients undergoing omalizumab treatment . Here we report the case of a patient who was able to reduce the dose of omalizumab supported by the measurement of the serum free IgE levels.
Term-course of the patient’s clinical data before and after treatment of omalizumab
Omalizumab 750 mg/month
Omalizumab 375 mg/month
White blood cell no. (×103)
Neutrophil no. (×103)
Lung function test
%FEV1.0 (% predicted)
At present, free IgE and IgE-omalizumab complexes cannot be distinguished using current clinical methods for measuring serum total IgE levels, like ImmunoCAP (Thermo Fisher Scientific, Uppsala, Sweden); thus, serum total IgE levels appear to increase following the administration of omalizumab [3, 4]. This is because of the 2.4-day half-life of human serum IgE compared to the 20-day half-life of IgE, which is longer because of IgE binding to the IgG1 antibody omalizumab.
Lowe et al.  have used mathematical models to predict that long-term omalizumab treatment may lower IgE production levels in their study of pharmacokinetic data from past clinical trials. According to the assessment using this model, the IgE production level is inhibited to a greater extent as the duration of omalizumab administration increases . A prospective study measuring the free IgE level of 30 patients undergoing omalizumab therapy over time, using the method of free IgE measurement that we developed, demonstrated that free IgE levels 1 year after initiating administration had gradually decreased . Furthermore, the speed at which the free IgE level decreases after initiating omalizumab has been demonstrated to have a possible association with the reactivity to omalizumab therapy . In the present case, the total IgE levels also gradually declined beginning at 4 weeks. I suggested that the IgE production levels were observed to gradually decrease after initiating omalizumab administration, but it is difficult to fully grasp the quantitative relationship because the total IgE level temporarily increases after initiating omalizumab (Fig. 1).
While the mechanism underlying the decrease in the serum total IgE level due to the continuation of omalizumab therapy remains unknown, there are several possible explanations. First, decrease of free IgE levels by omalizumab can lead to down regulation of FcεRI on mast cell and dendritic cells . Second, IgE production is promoted by Th2 cytokines and CD40 , omalizumab therapy may suppress the activation Th2 cells indirectly, thereby lowering IgE production. Third, the decreased expression of low-affinity IgE receptors on dendritic cells is also suggested to be potentially involved in decreasing IgE . Third, the decreased expression of CD23/FcεRII, one of the low-affinity IgE receptors, may also be involved in suppressing IgE production. CD23/FcεRII is known to play an important role in maintaining IgE homeostasis. Past clinical research on the anti-human CD23/FcεRII monoclonal antibody lumiliximab has demonstrated that the inhibition of CD23/FcεRII controls the human serum IgE level . The binding of CD23/FcεRII to IgE is reportedly inhibited by omalizumab bound to IgE . Moreover, sCD23/FcεRII expression is reported to increase in response to inflammation ; thus, it is also possible that the improvement in allergic inflammation lowers soluble CD23/FcεRII, which then decreases the induction of IgE production via CD23/FcεRII.
The serum free IgE levels would be the most reliable marker reflect the IgE production status in the patients treated with omalizumab. One of the benefits of the long-term use of omalizumab is the improvement of patients’ atopic status by reducing IgE productivity. Moreover, if IgE production can be suppressed, it is possible to re-adjust and reduce the dosage.
The present case shows the possibility of reducing the dose of omalizumab following its. Considering the high medical cost of omalizumab, reduction of the dose may be a viable option. In such a case, it is useful to measure the serum free IgE level to appropriately identify patients in whom the dose can be reduced. Because there are patients similar to the present study in whom serum free IgE levels temporarily increase following a dose reduction of omalizumab, it is recommended that their clinical courses be carefully monitored by observing their serum free IgE levels.
YG wrote the manuscript. YG, RI, SM, HH, YK provided clinical care to the patient. YG, RI and SM performed the experiments. SS, KM, IY, and SH revised the manuscript. All authors approved the final manuscript for publication. All authors read and approved the final manuscript.
YG and SH: personal fees/other from: AstraZeneka, Kyorin Pharma, Novartis Pharma, Boehringer Ingelheim, outside the submitted work. All other authors have declared no competing interests.
Availability of data and materials
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Consent for publication
The individual described in the above case report has completed and signed a consent form for publication and presentation.
We obtained written consent from the patient to have the measurement of serum free IgE. The measurement of serum free IgE was taken with the approval of the ethics committee of the Nihon University Itabashi Hospital (RK-120413-9, approved in 27 April 2012).
The measurement of the free IgE was supported by the Strategic Research Base Development Program for Private Universities subsidized by MEXT (S1511014).
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