Professor Liu Changshan
Chief physician
Master's supervisor
Director of the Department of Pediatrics and Director of the Department of Pediatrics, Second Hospital of Tianjin Medical University
Director of the Research Center for Child Respiratory and Asthma, Tianjin Medical University
Chairman of the Pediatric Branch of Tianjin Medical Association, Leader of the Respiratory Group, and Leader of the Asthma Collaboration Group
Vice Chairman of Allergy Branch of Tianjin Medical Association
Vice Chairman of The Allergy Branch of Tianjin Association of Integrative Traditional and Western Medicine
Vice Chairman of the Children's Health Committee of Tianjin Medical Doctor Association
Vice Chairman of Allergy Prevention and Control Branch of Tianjin Preventive Medicine Association
He is a member of the Pediatric Branch of the Chinese Medical Association, a member of the Respiratory Group, and the deputy leader of the Asthma Group
Member of the Allergy Branch of the Chinese Medical Association
Member of the Standing Committee of the Allergy Branch of the Chinese Association of Integrative Medicine and head of the Pediatric Group
Member of the Standing Committee of the Pediatrics Branch of Integrative Medicine of the Chinese Medical Doctor Association
Member of pediatrician branch of Chinese Medical Doctor Association
Member of the Allergy Physician Branch of the Chinese Medical Doctor Association
Bronchial asthma (asthma for short) is the most common chronic airway inflammatory disease in childhood, characterized by chronic airway inflammation and airway hyperreactivity, and a heterogeneous disease with clinical features such as recurrent wheezing, cough, shortness of breath, and chest tightness [1].
In recent years, the prevalence of asthma in children has continued to increase, and with the use of conventional asthma control drugs, some children with asthma are still poorly controlled. The 2010 National Epidemiological Survey showed that 77 percent of children with asthma had an acute asthma attack within one year [2]. Allergic asthma is the most common phenotype of asthma in children, accounting for more than 80% of asthma [3]. In addition, children with asthma have a high proportion of allergic diseases such as allergic rhinitis, urticaria, and atopic dermatitis, and the presence of comorbidities may also lead to poor responses to inhaled glucocorticoids (ICS)-long-acting beta2 agonists (LABAs)[1].
The recombinant humanized anti-immunoglobulin E (IgE) monoclonal antibody, omalizumab, is the world's first biologically targeted drug for the treatment of asthma. Clinical practice has shown that omalizumab has a good clinical effect on asthma complicated by allergic rhinitis, chronic urticaria, atopic dermatitis, etc., and the individualized application of the drug has also attracted clinical attention when the seasonal application and IgE level are too high [1].
So what are the points of attention of omalizumab in the clinical application of allergic asthma in children? On this issue, we have invited Professor Liu Changshan, director of the Department of Pediatrics of the Second Hospital of Tianjin Medical University, to find out for us!
What are the indications for the use of omalizumab in children?
Indications
Professor Liu Changshan pointed out, "Omalizumab is generally suitable for children aged 6 years and above for moderate to severe persistent allergic asthma whose symptoms are not effectively controlled after ICS-LABA treatment.
Omalizumab may be more effective if the following are present in children: < 90% of expected baseline forced expiratory volume (FEV1) at 1 second, ≥ 3 acute attacks in the year prior to treatment, ≥ 20 ppb of exhaled nitric oxide (FeNO), eosinophil count (EOS) ≥ 2%, body mass index (BMI) ≥ 25 kg/m2, and baseline EOS ≥ 260/mL or FeNO ≥ in adults and adolescents with severe asthma At 19.5 ppb."
In addition, ovalizumab is also indicated in children with moderate to severe allergic asthma who need to avoid or reduce the use of oral hormones and/or are reluctant to use ICS for long periods of time due to adverse reactions.
Can omalizumab be used in patients with allergic asthma complicated with other allergic diseases?
Allergic asthma with allergic rhinitis
Professor Liu Changshan said, "The Consensus on the Clinical Application of Omalizumab in Children with Allergic Asthma (hereinafter referred to as the "Consensus") affirms that Omalizumab can benefit adolescents aged ≥ 12 years of age and adults with allergic asthma and severe allergic rhinitis, and clearly states that patients with IgE-mediated allergic asthma and severe allergic rhinitis can be treated with omalizumab when they do not respond well to avoid allergens and basic drug therapy."
The dosage of omalizumab for severe allergic rhinitis is given every 2 or 4 weeks, with reference to the recommended dose for allergic asthma indications, and the recommended course of treatment is shown in Figure 1.
Figure 1. Recommended course of treatment for omalizumab for rhinitis[1]
Allergic asthma combined with atopic dermatitis
Professor Liu Changshan said: "A real Czech data shows that among 67 patients with severe allergic asthma combined with atopic dermatitis after receiving 12 months of omarizumab treatment, the rate of complete relief or significant improvement in atopic dermatitis was as high as 82.1%. Omalizumab has also been reported in mainland China for the treatment of asthma combined with severe atopic dermatitis [1]. It can be seen that omalizumab can improve the clinical symptoms of atopic dermatitis in a variety of ways." The consensus also indicates that omalizumab therapy may be considered when conventional treatment of children with asthma complicated by severe atopic dermatitis is ineffective. Treatment is currently recommended for more than 6 months [1].
Allergic asthma with chronic urticaria
Referring to allergic asthma complicated with chronic urticaria, Professor Liu Changshan mentioned: "There are many literature reports that omalizumab is significantly effective in patients with asthma complicated by chronic urticaria, which can improve both asthma symptoms and 7-day urticaria activity score. Studies have shown that 85% of patients treated with omalizumab for 1 year improve asthma-associated urticaria symptoms. Patients with allergic asthma complicated with chronic urticaria should be treated with omalizumab and should follow the dosage table of the Chinese asthma indications."
Allergic asthma is complicated by food allergies
For patients with severe IgE-mediated food allergies, Professor Liu Changshan said: "There is a benefit from anti-IgE therapy, and receiving omalizumab therapy can improve the tolerance to allergic foods and reduce the risk of severe allergic reactions after accidental exposure. Studies have confirmed that patients with severe asthma and food allergies have an 8.6-fold increase in the threshold for food allergies after 4 months of use of omalizumab, and some patients can even reintroduce allergic foods. As a result of reduced food restrictions, the patient's quality of life improved significantly."
Can omalizumab be used in other patients in addition to the treatment of these patients?
Seasonal applications
The consensus states that seasonal omalizumab therapy can prevent asthma exacerbations. Professor Liu said: "Studies have shown that short-term treatment with omarizumab for 3 months in summer and autumn can improve lung function and nasal symptoms in patients with moderate to severe asthma with allergic rhinitis, improve the quality of life of patients, and reduce the number of asthma attacks."
Fig. 2. Improvement of TNSS and AQLQ after 3 months and months of omalizumab treatment[4]
Studies have shown [5] that patients with moderate to severe asthma with refractory nasal polyps have had their asthma well controlled and their rhinitis symptom scores and quality of life scores have improved significantly after receiving omalizumab for 4 months, as shown in Figure 3.
Figure 3.3 Improvement of TPS and JRQLQ scores in patients with asthma complicated with chronic sinusitis with nasal polyps after 4 months of treatment with omalizumab[5]
Apply in children under 6 years of age
In addition to the seasonal use of omalizumab, Prof Liu clearly pointed out the question of whether omalizumab can be used in children under 6 years of age: "At present, omalizumab has not been approved for the treatment of children under 6 years of age worldwide, and there is limited evidence of large samples of use in children under 6 years of age. The minimum age of medication in children reported is currently 2 years, and no adverse events occurred during the period of medication. In addition, a phase II clinical study (NCT02570984) of omalizumab in children aged 2 to 6 years is underway, which recommends that, if clinically required, doses of 0.016 mg/kg·IU can be calculated based on the child's body mass and total IgE, and administered every 4 weeks."
In addition to the above two cases, Professor Liu also talked about the use of omalizumab in some other special populations: "Application in children with allergic asthma with a total IgE of > 1,500 IU/mL: There is currently no dose recommendation for patients with a total IgE > of 1,500 IU/mL in the Omalizumab instructions. According to data from the Omalizumab Pharmacokinetics/Pharmacokinetics (PK/PD) study, patients with a total IgE > 1,500 IU/mL are recommended to be administered at the maximum dose (600 mg every 2 weeks) for the purpose of reducing serum free IgE in patients after administration.
Application in allergen immunotherapy (AIT): Omalizumab can be used at different stages of AIT therapy depending on the condition. Pre-administration of omalizumab to enable AIT, combination with omalizumab to help AIT reach the dose maintenance phase, and omalizumab pretreatment to reduce the occurrence of serious adverse effects of cluster/impact immunotherapy. However, the dose and duration of omalizumab application in AIT needs to be further explored.
Allergic bronchopulmonary aspergillosis (ABPA): In recent years, domestic and foreign studies have shown that omalizumab therapy can significantly improve symptoms in patients with ABPA and reduce acute exacerbations and hospitalizations, reduce serum total IgE levels, reduce oral hormone doses, improve lung function, and improve quality of life. However, clinical studies in children have mostly reported cases, and there is currently no standardized dose recommendation for ABPA."
Is the efficacy and safety of omalizumab clinically proven in children?
In response to the question on the efficacy and safety of omalizumab in the treatment of allergic asthma in children, Prof Liu said: "Overall, combined with omalizumab add-on therapy based on ICS treatment is effective and safe for children with allergic asthma. A number of foreign multicenter, randomized, double-blind controlled studies have shown that children with moderate to severe allergic asthma (6 to 20 years old) combined with omalizumab add-on therapy (treatment course of 24 to 60 weeks) on the basis of ICS treatment can further improve asthma symptoms, reduce the rate of asthma exacerbations, and reduce the inhalation dose of ICS. A 2017 Japanese study looked at the efficacy and safety of long-term omalizumab add-on therapy in children with severe uncontrolled allergic asthma, with an average duration of nearly 117 weeks (47 to 151 weeks), and the results showed that omalizumab add-on therapy enabled 76% of children to achieve complete or good control of asthma, and asthma-related hospitalization and emergency rates decreased significantly. The incidence of adverse reactions did not increase cumulatively with prolonged use.
A large number of clinical studies and applications have confirmed that children aged 6 years and older are well tolerated when treated with omalizumab, and the incidence of adverse events is low, mostly mild to moderate, and the duration is short. Adverse reactions in children aged 6 to 12 years are mainly headache, fever and epigastric pain, and pain, swelling, erythema and itching at the injection site common at the age of 12 years and older, and mild arthralgia, fatigue, and dizziness can also occur. Omalizumab-related severe allergic reactions are rare, occurring in 0.1% to 0.2%, and no severe anaphylaxis has been reported in clinical applications in children."
summary
Omalizumab is generally indicated for patients with moderate to severe persistent asthma in ≥ 6 years of age who are unable to effectively control symptoms after ICS-LABA treatment, and in children with moderate to severe allergic asthma who need to avoid/reduce the use of oral hormones and/or are reluctant to use ICS for a long time due to adverse reactions. The consensus fully affirms the efficacy and safety of omalizumab in children with moderate to severe allergic asthma in ≥ 6 years old, and also proposes that the special application practice of omalizumab also has certain reference value for clinical work in other allergic diseases such as asthma complicated by allergic rhinitis, urticaria, atopic dermatitis and food allergies. The consensus clearly states that omarizumab can bring many improvements to children with allergic asthma, so what does the consensus say about its specific dosage, course of treatment, dose adjustment, and efficacy evaluation? Don't worry, the next article will answer you!
Content Review: Dan Liu
Project Review: Xu Chao
Legal Review: Xu Chao
Title image source: Stand Cool Helo
bibliography:
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Sha Li, Liu Chuanhe, Shao Mingjun, et al. Ten-year comparison of asthma diagnosis and treatment in urban children in China[J] . Chin J Pediatrics,2016,54 (3): 182-186. DOI: 10.3760/cma.j.issn.0578-1310.2016.03.005
[3]. Respiratory Allergy Group of Allergy Branch of Chinese Medical Association (preparation), Asthma Group of Respiratory Disease Branch of Chinese Medical Association. Guidelines for the Diagnosis and Treatment of Allergic Asthma in China (First Edition, 2019) [J] . Chin J Internal Medicine, 2019, 58(9): 636-655. DOI: 10.3760/cma.j.issn.0578-1426.2019.09.004.
Ma Tingting, Wang Xiangdong, Chen Yanlei, et al. Clinical efficacy and safety of omalizumab in the treatment of hay fever with moderate to severe asthma[J].Chinese Department of Otolaryngology, Head and Neck Surgery,2018,25(12):675-678.
[5]. Sui Haijing,Hu Yan,Chen Yudi,Geng Peng,Zhao Zuotao. Anti-IgE monoclonal antibody treatment of refractory sinusitis with nasal polyps in three cases[J].Chinese Journal of Otolaryngology Head and Neck Surgery,2021,56(2):150-152.DOI:10.3760/cma.j.cn115330-20201112-00864.