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Utility of serum anti-cetuximab immunoglobulin E levels to identify patients at a high risk of severe hypersensitivity reaction to cetuximab.

ABSTRACT: AIM:Cetuximab is an anti-epidermal growth factor receptor antibody used for the treatment of metastatic colorectal cancer and head and neck cancer. Hypersensitivity reactions (HSRs) are associated with cetuximab use. The aim of the study was to evaluate the utility of anti-cetuximab immunoglobulin E (IgE) detection in order to identify patients at risk of HSR to cetuximab. METHODS:We included patients ready to receive a first cetuximab infusion in a prospective cohort carried out at nine French centres. Pretreatment anti-cetuximab IgE levels were measured. We compared the proportion of severe HSRs in the low anti-cetuximab IgE levels (?29 IgE arbitrary units) subgroup with that in a historical cohort of 213 patients extracted from a previous study. RESULTS:Of the 301 assessable patients (mean age: 60.9 ± 9.3 years, head-and-neck cancer: 77%), 66 patients (22%) had high anti-cetuximab IgE levels, and 247 patients received cetuximab (including 38 with high anti-cetuximab levels). Severe HSRs occurred in eight patients (five grade 3 and three grade 4). The proportion of severe HSRs was lower in the low anti-cetuximab IgE levels subgroup vs. the historical cohort (3/209 [1.4%] vs. 11/213 [5.2%], odds ratio, 0.27, 95% confidence interval, 0.07-0.97), and higher in high vs. low anti-cetuximab IgE levels subgroup (5/38 [13.2%] vs. 3/209 [1.4%]; odds ratio, 10.4, 95% confidence interval, 2.4-45.6). Patients with severe HSRs had higher anti-cetuximab IgE levels than patients without reaction (median, 45 vs. 2 IgE arbitrary units, P = 0.006). CONCLUSIONS:Detection of pretreatment anti-cetuximab IgE is feasible and helpful to identify patients at risk of severe cetuximab-induced HSRs.

SUBMITTER: Dupont B

PROVIDER: S-EPMC5306475 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Utility of serum anti-cetuximab immunoglobulin E levels to identify patients at a high risk of severe hypersensitivity reaction to cetuximab.

Dupont Benoît B Mariotte Delphine D Dugué Audrey E AE Clarisse Bénédicte B Grellard Jean-Michel JM Babin Emmanuel E Chauffert Bruno B Dakpé Stéphanie S Moldovan Cristian C Bouhier-Leporrier Karine K Reimund Jean-Marie JM Di Fiore Frederic F Zanetta Sylvie S Mailliez Audrey A Do Pascal P Peytier Annie A Galais Marie-Pierre MP Florescu Carmen C Schott Roland R Le Mauff Brigitte B Gervais Radj R

British journal of clinical pharmacology 20161024 3

<h4>Aim</h4>Cetuximab is an anti-epidermal growth factor receptor antibody used for the treatment of metastatic colorectal cancer and head and neck cancer. Hypersensitivity reactions (HSRs) are associated with cetuximab use. The aim of the study was to evaluate the utility of anti-cetuximab immunoglobulin E (IgE) detection in order to identify patients at risk of HSR to cetuximab.<h4>Methods</h4>We included patients ready to receive a first cetuximab infusion in a prospective cohort carried out ...[more]

PMID: 27662818

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Project description:Background. Leprosy reactions are acute inflammatory episodes that occur mainly in the multibacillary forms of the disease. The reactions are classified as type 1 (reverse reaction) or type 2 (erythema nodosum leprosum). Leprosy-associated oxidative stress has been widely demonstrated. Several recent studies have shown uric acid (UA) to have antioxidative effects under pathologic conditions. The objective of this study was to assess serum levels of UA in patients with leprosy reactions, with the aim of monitoring their levels before and after treatment, compared with levels in leprosy patients without reactions. Methods. The study included patients aged 18-69 years assisted at a leprosy treatment reference center in the Central Region of Brazil. Patients who were pregnant; were using immunosuppressant drugs or immunobiologicals; or had an autoimmune disease, human immunodeficiency virus infection, acquired immune deficiency syndrome, or tuberculosis were excluded. Upon recruitment, all individuals were clinically assessed for skin lesions and neural or systemic impairment. Some patients had already completed treatment for leprosy, while others were still undergoing treatment or had initiated treatment after being admitted. The treatment of the reactional episode was started only after the initial evaluation. Laboratory assessments were performed upon admission (baseline) and at approximately 30 and 60 days (time points 1 and 2, respectively). Results. A total of 123 leprosy patients were recruited between June 2012 and June 2015; among them, 56, 42, and 25 presented with type 1, type 2, and no reactions, respectively. Serum UA levels were significantly reduced in patients with type 2 leprosy reactions compared with patients in the control group and remained lower in the two subsequent assessments, after initiation of anti-reaction treatments, with similar values to those recorded before the treatment. Discussion. The decreased serum UA levels in patients with type 2 leprosy reactions might be due to the consumption of UA to neutralize the enhanced production of oxygen- and nitrogen-reactive species that occurs during type 2 reactions. The maintenance of the reduced levels in the follow-up assessments may indicate persistence of oxidative stress in the initial post-treatment stages, despite improved clinical conditions. The results of this study suggest that serum UA may play an antioxidative role during type 2 leprosy reactions.

Project description:BackgroundOccupational exposures to chromium (Cr), which can have adverse effects on immune function, have not yet been extensively investigated. Hexavalent chromium (Cr (VI)), used in mineral tanning processes, poses a threat to the health of workers in the leather tanning industry.ObjectivesThe aim of the present study was to evaluate the effects of long-term Cr exposure on the physical health and immunological parameters of male tannery workers in Bangladesh compared with a control group.MethodsA health examination was performed with tannery workers (N=195) and control subjects (N=125) by physicians, demographic data were recorded in questionnaires and peripheral blood samples were collected. Serum Cr levels were analyzed by an atomic absorption spectrophotometer (AAS), immunoglobulin (Ig)G, IgA, and complement components C3 and C4 were determined by nephelometry, IgE was measured by sandwich enzyme-linked immunosorbent assay and complement function was assayed by bactericidal activity.ResultsThe mean duration of work exposure for the tanners was 9.4±7.1 years. Their body mass index (21.8±3.0 kg/m2), was not significantly different from the controls (22.7±3.2 kg/m2). The mean serum level of Cr in 30 long-term exposed tannery workers (26.97±21.11 μg/dL) was significantly higher than that of 30 randomly selected control subjects (7.38±6.81 μg/dL). The tannery workers had rough skin, rashes, itchy and decolorized skin, allergic diseases and respiratory illness, and had significantly lower levels of serum IgG, IgA, C3 and C4, but significantly higher levels of IgE than the controls. IgG, IgA and C3 levels were all inversely associated with Cr, while IgG, IgE and bactericidal activity showed an inverse correlation with duration of exposure.ConclusionsThe results of the present study suggest that chronic exposure to Cr is associated with impaired immune function in male tannery workers.Participant consentObtained.Ethics approvalThe present study was approved by the Ethical Review Committee of the faculty of Biological Sciences, University of Dhaka, Bangladesh.Competing interestsThe authors declare no competing financial interests.

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Dataset Information

Utility of serum anti-cetuximab immunoglobulin E levels to identify patients at a high risk of severe hypersensitivity reaction to cetuximab.

Publications

Utility of serum anti-cetuximab immunoglobulin E levels to identify patients at a high risk of severe hypersensitivity reaction to cetuximab.

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