Benoît Dupont

Anti-cetuximab IgE ELISA for identification of patients at a high risk of cetuximab-induced anaphylaxis

Cetuximab, a chimeric mouse-human IgG1 monoclonal antibody against the epidermal growth factor receptor, has proven effective in the treatment of metastatic colorectal cancer and squamous cell carcinoma of the head and neck. However, a high incidence of immediate hypersensitivity reactions (HSR) to cetuximab after the first infusion has been observed. We have developed a test for identification of patients likely to show treatment-related HSR to cetuximab. An enzyme-linked immunosorbent assay (ELISA) for detecting anti-cetuximab IgEs was developed and tested on serum samples collected from cancer patients before start of cetuximab treatment, and from healthy blood donors. Similar levels of anti-cetuximab IgE were detected in pre-treatment patient sera (24/92, 26.1%) and sera from healthy blood donors (33/117, 28.2%). HSR were observed in 14 out of the 92 patients (15.2%), and 8 of these (57.1%) were grade 3-4. Anti-cetuximab IgEs were detected in 7/8 of the patients (87.5%) with severe HSRs as compared with 14/78 patients (17.9%) with no HSR (p=0.0002). Predictive value of the anti-cetuximab IgE test for HSR events of grades 3-4 was calculated using Receiver Operating Characteristics analysis. With a cut-off value of 29 arbitrary units for the anti-cetuximab IgE, the ELISA test showed a sensitivity of 87.5%, specificity of 82.1%, positive predictive value of 33.3% and negative predictive value of 98.5%. Anti-cetuximab IgE ELISA detection could be a valuable tool to help the physician anticipate an anaphylaxis episode following cetuximab infusion and opt for a suitable alternative treatment.

Enteral nutrition in adult Crohn's disease : Present status and perspectives

Enteral nutrition has long been a therapeutic alternative often used in adult Crohns disease patients to obtain remission or clinical response, especially in those not responding to conventional therapy such as corticosteroids. However, the increasing use of immunosuppressors (6-mercaptopurine and azathioprine, methotrexate, etc.), and the advent of biotherapies (especially anti-tumor necrosis factor-alpha (TNF-alpha) antibodies), decreased its use in adult Crohns disease. Nevertheless, enteral nutrition remains of interest in patients presenting concomitant malnutrition (in particular in nonobstructed patients needing surgery), or in those intolerant or who failed to other therapeutics. In addition, recent studies provide data indicating its potential interest in maintenance therapy in selected patients groups. Finally, future research (in particular in the field of immuno- or pharmaconutrition) could lead to enteral formulas improvement, with better tolerance and acceptability, as well as increased efficacy.

Case Report About Fatal or Near-Fatal Hypersensitivity Reactions to Cetuximab: Anticetuximab IgE as a Valuable Screening Test

Hypersensitivity reactions are a classic side effect of cetuximab. We report the cases of three patients who developed life-threatening hypersensitivity to cetuximab, which could have been predicted by assessing the concentration of serum anticetuximab immunoglobulin (Ig)E. The anti-cetuximab IgE concentration could be an interesting test to predict which patients are at risk of experiencing severe hypersensitivity reactions to cetuximab.

Retrospective evaluation of prognostic score performances in cirrhotic patients admitted to an intermediate care unit

BACKGROUND The prognosis of cirrhotic patients in the Intensive Care Unit requires the development of predictive tools for mortality. We aimed to evaluate the ability of different prognostic scores to predict hospital mortality in these patients. METHODS A single-centre retrospective analysis was conducted of 281 hospital stays of cirrhotic patients at an Intermediate Care Unit between June 2009 and December 2010. The performance of the Simplified Acute Physiology Score (SOFA), the Simplified Acute Physiology Score (SAPS) II or III, Child-Pugh, Model for End-Stage Liver Disease (MELD), MELD-Na and the Chronic Liver Failure-Consortium Acute-on-Chronic Liver Failure score (CLIF-C ACLF) in predicting hospital mortality were compared. RESULTS Mean age was 58.2±12.1 years; 77% were male. The main cause of admission was acute gastrointestinal bleeding (47%). The in-hospital mortality rate was 25.3%. Receiver operating characteristic curve analyses demonstrated that SOFA (0.82) MELD-Na (0.82) or MELD (0.81) scores at admission predicted in-hospital mortality better than Child-Pugh (0.76), SAPS II (0.77), SAPS III (0.75) or CLIF-C ACLF (0.75). We then developed the cirrhosis prognostic score (Ci-Pro), which performed better (0.89) than SOFA. CONCLUSION SOFA, MELD and especially the Ci-Pro score show the best performance in predicting hospital mortality of cirrhotic patients admitted to an Intermediate Care Unit.

Efficacy of anti-TNF-alpha monoclonal antibodies in inflammatory bowel disease treatment

Pathogenesis of inflammatory bowel disease (IBD), including Crohns disease (CD) and ulcerative colitis (UC), continues to drive basic research to better decrypt their causal factor(s). Several key mediators involved in IBD pathogenesis have been identified and are considered as potential therapeutic targets. The best example of translational research (from bench to bedside) success is the demonstration that tumor necrosis factor (TNF)-alpha plays a critical role in IBD pathophysiology and that several monoclonal antibodies directed against TNF-alpha are effective tools in IBD treatment. Numerous high quality clinical tri- als have proven that monoclonal anti-TNF-alpha antibodies (infliximab, adalimumab, and certolizumab pegol) are of great therapeutic value in luminal and/or fistulizing CD or UC, both as induction and as maintenance treatment (health authority approval is dependent on the country and on the antibody being used). Therefore, it is not excessive to state that they have become the mainstay in IBD therapy in 2013. Nevertheless, some important questions related to their use (in particular their long-term use) should be answered in the coming years. This paper reviews the most important data on efficacy and tolerance, and also aims to highlight

Risk factors associated with hypersensitivity reactions to cetuximab: anti-cetuximab IgE detection as screening test

AIM To describe the factors associated with a high risk of a hypersensitivity reaction to cetuximab. PATIENTS & METHODS We retrospectively studied a cohort of patients living in Normandy (France) treated with cetuximab. RESULTS Among the 229 treated patients, 24 (10.5%) had a hypersensitivity reaction to cetuximab, including 11 grade 3-5 reactions. Detection of anti-cetuximab IgE could be performed in 108 patients. Anti-cetuximab IgE was found in 13 of 17 patients (76.5%) who had a hypersensitivity reaction to cetuximab compared with 17 of 91 control patients (18.7%; adjusted odds ratio: 14.99; 95% CI: 3.59-62.63). No clinical criteria predicted the risk of allergy to cetuximab. CONCLUSION Anti-cetuximab IgE may help physicians identify patients at risk of a hypersensitivity reaction to cetuximab.

Lupus et ischémie intestinale : une association de mauvais pronostic

Lelupus erythemateux systemique (LES) est une affection auto-immune non specifique d’organe dont les presentations cliniques peuvent etre multiples et variees. Parmi elles, des douleurs abdominales peu specifiques sont trouvees chez pres de 80 % des malades et peuvent etre la seule expression d’une ischemie mesenterique. De par leur manque de specificite, la frequence d’une atteinte lupique digestive est probablement sous-estimee, certaines series autopsiques rapportant jusqu’a 70 % d’atteintes peritoneales dont 10 % etaient pauci-symptomatiques. La morbidite et la mortalite de la maladie lupique sont correlees aux lesions de l’intestin grele ou du colon qui sont souvent liees a une vascularite mesenterique lupique evoluant vers l’ischemie intestinale aigue ou chronique. Ainsi, la vascularite mesenterique lupique constitue la principale cause a considerer precocement devant une douleur abdominale inhabituelle, prolongee ou intense, dans le but de reduire l’evolution vers l’infarctus mesenterique et ses complications telles que la perforation. Le pronostic depend donc d’un diagnostic precoce passant par la prise en compte de tout symptome digestif chez un patient atteint de lupus. La gravite potentielle de ces complications doit guider l’indication, au mieux d’une tomodensitometrie, ou a defaut d’une echographie abdominopelvienne en urgence en vue d’une prise en charge precoce et intensive. Au stade precoce, le traitement sera d’abord medical avec une place de choix pour la corticotherapie intraveineuse suivie d’un relai par voie orale voire ulterieurement par la prescription d’immunosuppresseurs. Toutefois, la chirurgie peut etre necessaire si le patient est vu au stade de complication.Cette mini-revue a pour objectif de rappeler l’importance qu’il faut accorder (« surveillance armee ») a tout symptome digestif survenant chez un patient lupique.