Allergy to monoclonal antibodies: cutting-edge desensitization methods for cutting-edge therapies

Hong, Deli; Bankova, Lora G.; Cahill, Katherine N.; Kyin, Timothy; Castells, Mariana

doi:10.1586/eci.11.75

Cited by 78 publications

(56 citation statements)

References 29 publications

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“…Desensitization has been a reliable alternative to discontinuation of first-line drugs and different desensitization protocols have been developed [5,6,7,8,9,12,13,14,16,17]. Rapid desensitization was performed with rituximab because it was the most effective option for our patients with hematologic malignancies.…”

Section: Discussionmentioning

confidence: 99%

“…We used the 12-step protocol generated by the BWH. Such a protocol has been proven to induce temporary tolerance to drugs by inducing an HSR [6,7,12,13]. …”

Section: Discussionmentioning

confidence: 99%

“…HSRs to biologics can occur during the first exposure (i.e., cetuximab, trastuzumab, and rituximab) or after multiple exposures (i.e., rituximab and infliximab) [6,12,13,18]. In rituximab-focused studies, the majority of patients who are hypersensitive react to the drug at the first exposure [6,18,19,20].…”

Section: Discussionmentioning

confidence: 99%

“…For patients with grade III reactions with respiratory or cardiac arrest, a protocol modification was performed using a 16-step protocol in which a 4th bag was added with X/1,000 dilution, or half doses of the drug were given during the first desensitization and then based on the patient's tolerance; the next desensitization was performed with the total target dose of the drug [5,7,12,13,14]. …”

Section: Methodsmentioning

confidence: 99%

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Rapid Drug Desensitization with Biologics: A Single-Center Experience with Four Biologics

Bavbek

Kendirlinan²,

Çerçi³

et al. 2016

Int Arch Allergy Immunol

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Background: Rapid drug desensitization (RDD) induces a temporary tolerance to biologics which induce hypersensitivity reactions (HSRs). Data are limited regarding the use of RDD outside the USA. Our purpose was to report our data on RDD to rituximab, infliximab, cetuximab, and trastuzumab. Methods: The study was conducted as a retrospective chart review of patients with symptoms of HSRs to biologics. HSRs were classified as grades I, II, and III, based on their severity. Skin-prick tests/intradermal tests (IDTs) were performed with the implicated biologics. The 12-step RDD protocol was used. Results: The study group comprised 11 women and 6 men (mean age: 47 ± 11.7 years). Fourteen patients experienced HSRs to rituximab; 3 had HSRs to cetuximab, infliximab, and trastuzumab, respectively. HSRs to cetuximab, infliximab, and trastuzumab occurred during the first infusion and were all grade III. Twelve of the 14 patients with rituximab hypersensitivity had a reaction during the first infusion; 10 patients had grade II reactions and 4 had grade III reactions. Respiratory symptoms were the most frequent presentation of HSR. Skin tests with rituximab were performed on 10 patients; only 3 resulted in positive IDTs (with 1:100 dilutions) and the other tests were negative as were those performed with the other biologics. Of 96 RDDs, 89 desensitizations were performed with rituximab, 5 with cetuximab, 1 with infliximab, and 1 with trastuzumab. There were 12 (13.5%) breakthrough reactions, all of which were associated with rituximab and were less severe than the initial reactions. Conclusion: RDD was found to be safe and effective in the largest case series of RDDs with biologics in our country, Turkey.

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Section: Discussionmentioning

confidence: 99%

“…We used the 12-step protocol generated by the BWH. Such a protocol has been proven to induce temporary tolerance to drugs by inducing an HSR [6,7,12,13]. …”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Rapid Drug Desensitization with Biologics: A Single-Center Experience with Four Biologics

Bavbek

Kendirlinan²,

Çerçi³

et al. 2016

Int Arch Allergy Immunol

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“…This is consistent with previous reports of utilization of such procedure in some other cases of non IgE-mediated drug reactions. 8,9 To our knowledge this is the first report of skin testing, graded challenge and desensitization protocols to VWF products. These procedures and protocols may be of benefit in other patients with reactions to VWF products.…”

Section: Author Manuscript Author Manuscriptmentioning

confidence: 91%

Skin Testing, Graded Challenge and Desensitization to Von Willebrand Factor (vWF) Products in Type III Von Willebrand Disease (VWD)

Platt

D'Angelo

Neufeld

et al. 2015

Journal of Allergy and Clinical Immunology

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SummaryThis is the first report of skin testing, graded challenge and desensitization for VWF replacement products in patients with VWF deficiency. Patients who have experienced reactions to VWF products may benefit from these protocols. Keywordsdesensitization; drug allergy; pediatric patient; skin testing; anaphylaxis; von Willebrand factor; factor VIII To the editor von Willebrand disease (VWD) is the most common inherited disorder of hemostasis, affecting approximately 1 in 1000 individuals in the population. VWD is caused by defects in the quantity or quality of von Willebrand factor (VWF), a multimeric glycoprotein that binds to collagen and platelets upon activation, leading to hemostasis. Clinical manifestations vary greatly between patients, and can range from mild mucocutaneous bleeding to musculoskeletal bleeding and stroke. 1,2 Type III VWD is the most severe form of the disorder and can be fatal. It affects about one in 1 million live births. 1 For these severe cases of VWD there are a variety of VWF replacement products. Unfortunately, a small number of patients, generally those with severe deleterious mutations, develop alloantibodies (most commonly polyclonal IgG) to such products, with estimates ranging from 5.8% to 9.5%. 3,4 Such antibodies, called inhibitors, Address correspondence to: Ana Dioun Broyles, Division of Immunology, Boston Children's Hospital, Boston, Massachusetts 02115, USA, Phone: 617-355 -6117, ana.broyles@childrens.harvard.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. 5 There have also been reports of patients experiencing symptoms consistent with anaphylaxis when exposed to VWF or factor VIII replacement products (some of which contain VWF). [3][4][5][6] Prior studies have identified immune complex formation and complement activation as mediators of these reactions, rather than IgE. 3 Here, we describe two VWD patients with inhibitory alloantibodies to VWF who developed VWF infusion reactions, some of which were clinically consistent with anaphylaxis given documentation of urticaria, respiratory distress and hypotension. Evaluation and treatment was ultimately made possible through skin prick and intradermal testing, graded challenge and/or desensitization. HHS Public AccessPatient 1 is a 2-year-old male from the United Arab Emirates who is one of several affected siblings with Type III VWD from a consanguineous marriage. Genetic analysis revealed a large deletion in the VWF gene (c.658_7887del: p.G220_L2629del). He required frequent VWF replacement infusions for recurrent bleeding episodes. Given the high frequency of these bl...

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Risk of Hypersensitivity to Biologic Agents Among Medicare Patients With Rheumatoid Arthritis

Yun

Xie

Beyl

et al. 2017

Arthritis Care & Research

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Background Hypersensitivity reactions (HSRs) can occur with any of the available biologic drugs used to treat rheumatoid arthritis (RA). We compared drug-specific risks for HSR among RA patients enrolled in the US Medicare program. Methods Using Medicare data, we identified new users of infused infliximab, abatacept, rituximab, tocilizumab, golimumab, and injected biologics. After identifying HSRs using validated algorithms, for each biologic, we calculated cumulative incidence over 6 months and incidence rates (IR) within 0–1, 2–14 and 15–30 days of administration. For each biologic administration, follow-up started on the infusion/injection date and ended at the earliest of HSR, subsequent biologic administration, death, coverage loss, 30-day follow-up, or 12/31/2013. Adjusted robust Poisson regression was used to compare the HSR risks across biologics. Sensitivity analysis was conducted using a nested case-crossover design. Results We identified 725,591 biologic administrations and 248 HSRs among 80,587 new biologic users. Of these, 26.9% were for IV abatacept, 4.6% rituximab, 5.8% IV tocilizumab, 22.9% infliximab, and 39.7% injectable anti-TNFi. The cumulative incidence of HSRs over 6 months for all biologics was low (< 1%). The IRs for HSR ranged from 2.4 (with abatacept) to 239.5 (with rituximab) per 106 per person days. After adjustment, and using injectable anti-TNF during 0–30 days as the referent, rituximab, infliximab, abatacept, and tocilizumab infusions were associated a significant higher risk of HSR. Sensitivity analysis yielded similar results. Conclusion Among RA patients taking biologics, rituximab and infliximab were most strongly associated with HSRs. The absolute IRs of HSR events for all biologic exposures were low.

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Allergy to monoclonal antibodies: cutting-edge desensitization methods for cutting-edge therapies

Cited by 78 publications

References 29 publications

Rapid Drug Desensitization with Biologics: A Single-Center Experience with Four Biologics

Rapid Drug Desensitization with Biologics: A Single-Center Experience with Four Biologics

Skin Testing, Graded Challenge and Desensitization to Von Willebrand Factor (vWF) Products in Type III Von Willebrand Disease (VWD)

Risk of Hypersensitivity to Biologic Agents Among Medicare Patients With Rheumatoid Arthritis

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