The association of omalizumab and oral immunotherapy (OIT) has proved to be efficient and safe in patients with food allergy (FA), but the long-term effect and the effect on severe patients have not been proved. The aims of the study are: 1) to identify, by a retrospective analysis of patients with a severe milk allergy, the risk factors for OIT’s failure, 2) to evaluate, by a prospective study, the change of tolerance during treatment with omalizumab in those patients who previously failed OIT. After revision of literature, we decided to consider severe only patients older then 5 years and with levels of specific IgE≥ 85kUA/L. By revision of discharge letters, we selected all the severe patients who undergone OTI for milk at our Institute and, for each patient, we recorded data about onset and severity of FA, allergological tests and hospital phase of OIT. Then, by phone interview, we collected data about the home phase of OTI. We decided to include into the prospective phase of the study only patients who stopped OIT because of reactions and who had moderate-severe asthma, because, for these patients, the Italian Health National System provides omalizumab free of charge to improve asthma control. For all included patients, allergology tests and an oral provocation test (OPT) with milk has been repeated: patients who tolerated less than 10mL of milk have been enrolled to start anti-IgE treatment. After 8 weeks of treatment with omalizumab, an OPT has been repeated. After it the patient continued both omalizumab and OTI at home, gradually increasing milk amount. After 11 months of treatment, milk intake has prudentially been reduced of 30% and at month 12 anti-IgE drug has been stopped, continuing instead the milk intake, but without increases. After revision of discharge letters, we identified 135 patients; of them 119 were available for phone interview. Among these patients, 37.8 % were on unrestricted diet, 25.2 % were still underway with SOTI and 36.9% have completely suspended SOTI because of revulsion for milk or severe or frequent reactions. After statistical analysis, it appears that the probability to stop SOTI is higher for older patients (> 10 years) and for those who had asthma and many reactions during hospital phase of OIT. Moreover it seems that patients who reached a low dose of milk (< 10mL) during hospital phase of OIT are at higher risk to suspend OIT even if statistically significance has not been reached for this aspect. Among the 33 patients who weren’t on unrestricted diet because of reactions, 13 patients were excluded, so 20 patients were eligible for the study. Of these, 9 patients accepted to participate to the study and 11 refused. Of these 9 patients: 1 patient was excluded because he tolerated more than 10mL of milk at OPT, 4 patients are currently under treatment and 4 patients are waiting to start it. After 8 weeks of omalizumab, all the 4 treated patients have reached a dose of milk higher than the one tolerated at enrollment. During home phase, all of them reached higher doses of milk than in the previous attempt of OIT, with great decrease of reactions. No side effect of omalizumab was recorded. All patients showed an improvement in quality of life. Currently, only 1 patient has stopped omalizumab: after 2 months he has had no reactions to his usual dose of milk. In conclusion, we can confirm that omalizumab is safe and that it can improve the result of OTI also in patients with severe milk allergy, both increasing tolerated milk dose and reduction of severe reactions. Future follow-up will show the effect of this approach on long term tolerance.
Nei pazienti con allergia alimentare (AA) l’associazione dell’omalizumab, un anticorpo monoclonale anti IgE, all’immunoterapia orale (OIT) ha dato buoni risultati, sia in termini di efficacia che di sicurezza; non è noto tuttavia l’esito di tale approccio nel lungo termine e nei pazienti con AA severa. Lo studio ha 2 obiettivi principali: 1) individuare i fattori di rischio per il fallimento dell’OIT, attraverso un’analisi retrospettiva dei pazienti con severa allergia alle proteine del latte vaccino (APLV); 2) valutare, attraverso una fase prospettica, l’andamento della tolleranza durante la terapia con omalizumab, nei pazienti con severa APLV che hanno fallito un precedente tentativo di OIT. Dopo revisione della letteratura, si è stabilito di considerare severi i pazienti che presentavano età ≥ 5 anni e livelli di IgE specifiche ≥85kUA/L. Sono state quindi revisionate le cartelle cliniche dei pazienti ricoverati con AA severa per raccogliere i dati riguardanti l’esordio e la gravità dell’AA, gli esami specifici e l’esito della fase ospedaliera dell’OIT. Tramite intervista telefonica, sono stati raccolti i dati sull’andamento domiciliare dell’OIT. Nella fase prospettica sono stati inclusi solo i pazienti che avevano sospeso l’OIT a causa di reazioni e che presentavano un’asma moderata\severa, condizione per cui è autorizzata da parte del SSN la somministrazione dell’omalizumab. A tutti i pazienti inclusi è stato ripetuto il test di provocazione orale (TPO): se la dose tollerata di LV era inferiore a 10mL è stato proposto l’omalizumab. Dopo 8 settimane di trattamento col solo omalizumab, è stato ripetuto il TPO. Successivamente il paziente ha continuato a domicilio l’omalizumab e l’assunzione del LV, aumentando gradualmente la dose. L’omalizumab è stato proseguito per un totale di 12 mesi. All’11° mese di trattamento la dose di LV assunta è stata ridotta prudenzialmente del 30% e mantenuta successivamente stabile. Dall’analisi delle lettere di dimissione sono stati individuati 135 pazienti, di cui 119 erano disponibili al follow-up. Di questi, il 37.8% era in dieta libera, il 25.2% stava continuando l’OIT e il 36.9% aveva sospeso l’OIT per repulsione nei confronti del LV o per reazioni. Dall’analisi dei dati è emerso che i pazienti più grandi (> 10 anni), che presentano broncospasmo e un numero elevato di reazioni durante la fase ospedaliera dell’OIT, hanno una probabilità maggiore di sospendere l’OIT. Inoltre sembrerebbe che l’essere dimessi con una dose di latte < 10mL aumenti il rischio di sospendere l’OIT, anche se non è stata raggiunta la significatività statistica per questo punto. Dei 33 pazienti che hanno sospeso l’OIT per reazioni, 13 sono stati esclusi; tra i 20 pazienti candidabili alla fase prospettica, 11 hanno rifiutato di partecipare allo studio. Dei 9 pazienti che hanno accettato, 1 ha tollerato più di 10mL al TPO, 4 sono attualmente in trattamento e 4 rimangono in attesa di ricovero. Dopo 8 settimane di terapia con omalizumab, tutti i 4 pazienti in trattamento hanno tollerato dosi maggiori di LV rispetto a quelle tollerate al TPO eseguito al momento dell’arruolamento. Durante la fase domiciliare, tutti sono riusciti ad aumentare la quota di LV tollerata, raggiungendo dosi maggiori di quelle del precedente tentativo di OIT, con netta diminuzione delle reazioni presentate. Non sono stati riscontrati effetti collaterali dell’omalizumab. Tutti i pazienti hanno riportato un miglioramento della qualità di vita. Attualmente un solo paziente ha sospeso il farmaco e, dopo 2 mesi, non ha presentato reazioni alla dose di LV raggiunta. In conclusione, l’omalizumab si è dimostrato efficace, anche nei pazienti con allergia severa al LV, nell’aumentare la dose di LV tollerata durante l’OIT e nel ridurre le reazioni durante l’OIT. È necessario un follow-up più lungo per verificare l’efficacia di tale approccio nel lungo termine.
Caratterizzazione clinica e molecolare e risposta alla terapia biologica con anticorpi monoclonali anti IgE di pazienti con allergia alimentare a rischio di vita resistenti all'induzione della tolleranza alimentare tramite desensibilizzazione alimentare / Benelli, Elisa. - (2020 Oct 23).
Caratterizzazione clinica e molecolare e risposta alla terapia biologica con anticorpi monoclonali anti IgE di pazienti con allergia alimentare a rischio di vita resistenti all'induzione della tolleranza alimentare tramite desensibilizzazione alimentare.
BENELLI, ELISA
2020-10-23
Abstract
The association of omalizumab and oral immunotherapy (OIT) has proved to be efficient and safe in patients with food allergy (FA), but the long-term effect and the effect on severe patients have not been proved. The aims of the study are: 1) to identify, by a retrospective analysis of patients with a severe milk allergy, the risk factors for OIT’s failure, 2) to evaluate, by a prospective study, the change of tolerance during treatment with omalizumab in those patients who previously failed OIT. After revision of literature, we decided to consider severe only patients older then 5 years and with levels of specific IgE≥ 85kUA/L. By revision of discharge letters, we selected all the severe patients who undergone OTI for milk at our Institute and, for each patient, we recorded data about onset and severity of FA, allergological tests and hospital phase of OIT. Then, by phone interview, we collected data about the home phase of OTI. We decided to include into the prospective phase of the study only patients who stopped OIT because of reactions and who had moderate-severe asthma, because, for these patients, the Italian Health National System provides omalizumab free of charge to improve asthma control. For all included patients, allergology tests and an oral provocation test (OPT) with milk has been repeated: patients who tolerated less than 10mL of milk have been enrolled to start anti-IgE treatment. After 8 weeks of treatment with omalizumab, an OPT has been repeated. After it the patient continued both omalizumab and OTI at home, gradually increasing milk amount. After 11 months of treatment, milk intake has prudentially been reduced of 30% and at month 12 anti-IgE drug has been stopped, continuing instead the milk intake, but without increases. After revision of discharge letters, we identified 135 patients; of them 119 were available for phone interview. Among these patients, 37.8 % were on unrestricted diet, 25.2 % were still underway with SOTI and 36.9% have completely suspended SOTI because of revulsion for milk or severe or frequent reactions. After statistical analysis, it appears that the probability to stop SOTI is higher for older patients (> 10 years) and for those who had asthma and many reactions during hospital phase of OIT. Moreover it seems that patients who reached a low dose of milk (< 10mL) during hospital phase of OIT are at higher risk to suspend OIT even if statistically significance has not been reached for this aspect. Among the 33 patients who weren’t on unrestricted diet because of reactions, 13 patients were excluded, so 20 patients were eligible for the study. Of these, 9 patients accepted to participate to the study and 11 refused. Of these 9 patients: 1 patient was excluded because he tolerated more than 10mL of milk at OPT, 4 patients are currently under treatment and 4 patients are waiting to start it. After 8 weeks of omalizumab, all the 4 treated patients have reached a dose of milk higher than the one tolerated at enrollment. During home phase, all of them reached higher doses of milk than in the previous attempt of OIT, with great decrease of reactions. No side effect of omalizumab was recorded. All patients showed an improvement in quality of life. Currently, only 1 patient has stopped omalizumab: after 2 months he has had no reactions to his usual dose of milk. In conclusion, we can confirm that omalizumab is safe and that it can improve the result of OTI also in patients with severe milk allergy, both increasing tolerated milk dose and reduction of severe reactions. Future follow-up will show the effect of this approach on long term tolerance.File | Dimensione | Formato | |
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