LETTERS TO THE EDITOR
|Year : 2022 | Volume
| Issue : 6 | Page : 1210-1213
Successful rapid desensitization of a pediatric multiple sclerosis patient with anaphylaxis to ocrelizumab
Hatice B G. Karaaslan1, Sezin Aydemir1, Ceren B Amirov2, Tugce D Dilek2, Zerengiz Bayramli1, Sema Saltik2, Ayca Kiykim1, Haluk Cokugras1
1 Department of Pediatric Immunology and Allergy, Istanbul University-Cerrahpasa, Istanbul, Turkey
2 Department of Pediatric Neurology, Istanbul University-Cerrahpasa, Istanbul, Turkey
|Date of Submission||13-Jun-2022|
|Date of Decision||05-Oct-2022|
|Date of Acceptance||06-Oct-2022|
|Date of Web Publication||17-Nov-2022|
Department of Pediatric Immunology and Allergy, Istanbul University, Cerrahpasa, Istanbul
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
G. Karaaslan HB, Aydemir S, Amirov CB, Dilek TD, Bayramli Z, Saltik S, Kiykim A, Cokugras H. Successful rapid desensitization of a pediatric multiple sclerosis patient with anaphylaxis to ocrelizumab. Ann Indian Acad Neurol 2022;25:1210-3
|How to cite this URL:|
G. Karaaslan HB, Aydemir S, Amirov CB, Dilek TD, Bayramli Z, Saltik S, Kiykim A, Cokugras H. Successful rapid desensitization of a pediatric multiple sclerosis patient with anaphylaxis to ocrelizumab. Ann Indian Acad Neurol [serial online] 2022 [cited 2023 Jan 27];25:1210-3. Available from: https://www.annalsofian.org/text.asp?2022/25/6/1210/361412
Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease of the central nervous system. As a result of chronic inflammation and neurodegeneration, disability occurs, especially in adolescents and young adults. Pediatric onset MS comprises 3%-5% of all cases. Recent studies have shown that B-cell–mediated autoantigen presentation can cause T-cell activation in the pathogenesis of MS. Monoclonal antibodies are increasingly used in the treatment of inflammatory diseases and malignancies. Biological agents, including their own proteins, which are perceived by the immune system as foreign antigens, can elicit an immune response. Originally, biological agents tended to be more immunogenic due to their higher content of nonhuman proteins (e.g., chimeric structures). However, over time, the content of proteins resembling human proteins increased and their immunogenicity decreased.
Ocrelizumab is a humanized monoclonal antibody that targets CD20-positive B-cells and was approved in 2017 for the treatment of relapsing-remitting and progressive MS. Mild infusion-related reactions occur in 1/3 of ocrelizumab-treated patients. Although treatment can be continued for mild reactions, more severe reactions lead to treatment discontinuation. In particular, life-threatening type 1 hypersensitivity reactions such as anaphylaxis lead to treatment discontinuation. However, continuation of treatment is critical for reducing morbidity in patients with MS. Rapid drug desensitization allows continuation of treatment in patients who develop a type 1 hypersensitivity reaction without an alternative drug option., Here, we present an adolescent patient who developed anaphylaxis during the first infusion of ocrelizumab and was subsequently treated successfully and safely with rapid drug desensitization.
A 14-year-old female patient with relapsing remitting MS, was admitted to our clinic to receive ocrelizumab. In her medical history, the patient's first clinical attack was observed at the age of 13 years as an optic neuritis of the left eye. She was diagnosed as a pediatric onset relapsing remitting MS as per International Pediatric Multiple Sclerosis Study Group and McDonald 2017 diagnostic criteria. She had started disease modifying treatment with interferon beta-1b (INF beta-1b), an immunomodulatory agent that is considered a first-line agent. Despite treatment with INF beta-1b, she had three clinical MS attacks within nine months [Figure 1]. High-dose steroids and plasmapheresis also did not improve. Therefore, the treatment was escalated to monoclonal antibody therapy, which is the second-line disease modifying treatment. Because the patient's serum was positive for John Cunningham virus antibodies, ocrelizumab was considered appropriate given the risk of progressive multifocal leukoencephalopathy. Because ocrelizumab is not approved by Turkish Ministry of Health for pediatric MS patients, special approvals from Turkish Ministry of Health, patient, and her parents were granted before the onset of treatment.
After premedication with paracetamol, diphenhydramine, and 100 mg of intravenous methylprednisolone, 300 mg of ocrelizumab was administered. During the first hour of infusion, the patient developed a diffuse urticarial rash, severe dyspnea, and bronchospasm. Hypotension and tachycardia were not observed. The patient was classified as anaphylaxis and received appropriate treatment. The patient underwent risk stratification and was classified as Brown classification grade 3 immediate hypersensitivity reaction (IHR).,
In the absence of alternative treatment, 300 mg ocrelizumab treatment was administered with a 12-step rapid desensitization protocol, as summarized in [Table 1]. Before rapid drug desensitization (RDD), she was premedicated with methylprednisolone and pheniramine maleate and the protocol was performed without reactions. After six months, the patient successfully received a new infusion with a 600-mg dose of ocrelizumab after dose adjustment as per the protocol shown in [Table 2].
We present the first case of an adolescent who was successfully desensitized with ocrelizumab after anaphylaxis. Although life-threatening reactions such as anaphylaxis are a serious risk during treatment, discontinuation or modification of MS treatment may worsen the condition. Reactions occurring during or after treatment with monoclonal antibodies can be classified as infusion-related reactions, cytokine-release reactions, type 1 hypersensitivity reactions (IgE-mediated or non-IgE–mediated), mixed reactions, delayed hypersensitivity reactions (type 4), and rarely type 3 hypersensitivity reactions.
Infusion-related reactions occur within a short time after infusion and are usually dependent on the rate of infusion. They are milder than type 1 hypersensitivity reactions and cytokine release reactions, and the severity can be reduced by subsequent administrations.
Reactions due to cytokine release are usually self-limiting and can be prevented by premedication. They present a broad symptom profile with fever, tachycardia, flushing, chills, dyspnea, nausea, and vomiting and often occur during infusion and especially during the first infusion.
Type 1 hypersensitivity reactions include the findings of early hypersensitivity reactions as per the Brown classification. Findings such as urticaria, angioedema, pruritus, hypotension, shortness of breath, and cardiac or respiratory arrest are observed as a result of mast cell activation occurring through IgE-mediated or non-IgE–mediated mechanisms.
In rare cases, delayed-type (type 4) hypersensitivity reactions are also observed. Type 4 hypersensitivity reactions account for < 5% of reactions triggered by monoclonal antibodies and usually occur 12-24 hours after infusion. Type 3 reactions are the Arthus reaction or serum sickness and are very rare.
Our patient was classified as a type 1 reaction because she had severe bronchospasm and urticaria. In ORATORIA trial, where patients treated with ocrelizumab were evaluated by Mayer et al., severe infusion-related reactions were observed in two patients but were not defined as type 1 reactions. Clements et al. had previously presented two cases at a scientific meeting. One patient, who suffered from hypoxia, chest pain, and itching in the throat and ears, and the other, who developed urticaria, were subsequently successfully desensitized with ocrelizumab. The case report by Aun et al. describes a patient with urticaria and angioedema after the first infusion and successful desensitization. To our knowledge, this is the first case of an adolescent in whom successful and safe desensitization was performed after anaphylaxis.
We could not perform skin prick tests because our patient needed urgent treatment. Therefore, we could not prove whether the reaction was IgE-mediated. However, in all type 1 hypersensitivity reactions, whether IgE-mediated or not, treatment can be continued with rapid desensitization.
In conclusion, for the continuation of ocrelizumab treatment in a pediatric MS patient with type 1 hypersensitivity reactions during ocrelizumab infusion, it is possible to successfully and safely perform rapid desensitization. In this way, treatment can be continued and exacerbation of the disease prevented. For this reason, the presentation of a successful rapid desensitization treatment is important for the exchange of experiences.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2]