Dataset Information

A Phase 2 Randomized Controlled Multisite Study Using Omalizumab-facilitated Rapid Desensitization to Test Continued vs Discontinued Dosing in Multifood Allergic Individuals.

ABSTRACT: Background:As there is limited data on the sustainability of desensitization of multifood-oral immunotherapy (multifood-OIT), we conducted a multisite multifood-OIT study to compare the efficacy of successful desensitization with sustained dosing vs discontinued dosing after multifood-OIT. Methods:We enrolled 70 participants, aged 5-22?years with multiple food allergies confirmed by double-blind placebo-controlled food challenges (DBPCFCs). In the open-label phase of the study, all participants received omalizumab (weeks 1-16) and multi-OIT (2-5 allergens; weeks 8-30) and eligible participants (on maintenance dose of each allergen by weeks 28-29) were randomized 1:1:1 to 1?g, 300?mg, or 0?mg arms (blinded, weeks 30-36) and then tested by food challenge at week 36. Success was defined as passing 2?g food challenge to at least 2 foods in week 36. Findings:Most participants were able to reach a dose of 2?g or higher of each of 2, 3, 4, and 5 food allergens (as applicable to the participant's food allergens in OIT) in week 36 food challenges. Using an intent-to-treat analysis, we did not find evidence that a 300?mg dose was effectively different than a 1?g dose in maintaining desensitization, and both together were more effective than OIT discontinuation (0?mg dose) (85% vs 55%, P?=?0.03). Fifty-five percent of the intent-to-treat participants and 69% of per protocol participants randomized to the 0?mg arm showed no objective reactivity after 6?weeks of discontinuation. Cross-desensitization was found between cashew/pistachio and walnut/pecan when only one of the foods was part of OIT. No statistically significant safety differences were found between the three arms. Interpretation:These results suggest that sustained desensitization after omalizumab-facilitated multi-OIT best occurs through continued maintenance OIT dosing of either 300?mg or 1?g of each food allergen as opposed to discontinuation of multi-OIT. Funding:Sean N. Parker Center for Allergy and Asthma Research at Stanford University, Jeff and MacKenzie Bezos, NIAID AADCRC U19AI104209. Trial Registration Number:ClinicalTrials.gov number, NCT02626611.

SUBMITTER: Andorf S

PROVIDER: S-EPMC6537534 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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A Phase 2 Randomized Controlled Multisite Study Using Omalizumab-facilitated Rapid Desensitization to Test Continued <i>vs</i> Discontinued Dosing in Multifood Allergic Individuals.

Andorf Sandra S Purington Natasha N Kumar Divya D Long Andrew A O'Laughlin Katherine L KL Sicherer Scott S Sampson Hugh H Cianferoni Antonella A Whitehorn Terri Brown TB Petroni Daniel D Makhija Melanie M Robison Rachel G RG Lierl Michelle M Logsdon Stephanie S Desai Manisha M Galli Stephen J SJ Rael Efren E Assa'ad Amal A Chinthrajah Sharon S Pongracic Jacqueline J Spergel Jonathan M JM Tam Jonathan J Tilles Stephen S Wang Julie J Nadeau Kari K

EClinicalMedicine 20190121

<h4>Background</h4>As there is limited data on the sustainability of desensitization of multifood-oral immunotherapy (multifood-OIT), we conducted a multisite multifood-OIT study to compare the efficacy of successful desensitization with sustained dosing <i>vs</i> discontinued dosing after multifood-OIT.<h4>Methods</h4>We enrolled 70 participants, aged 5-22 years with multiple food allergies confirmed by double-blind placebo-controlled food challenges (DBPCFCs). In the open-label phase of the st ...[more]

PMID: 31193674

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Project description:Omalizumab is licensed as add-on therapy for patients with severe allergic asthma. Response is in most studies scored by the physician's global evaluation of treatment effectiveness (GETE). A good clinical and validated parameter for treatment response is currently missing. Also, there are no established criteria for identifying patients who will respond to omalizumab based on pre-treatment characteristics. The Dutch National Omalizumab in Asthma Registry was developed in 2011 to better evaluate inclusion criteria and measure treatment response after 4 months.This is a "real world" prospectively designed, observational data registry in which the outcomes of patients who received omalizumab between 2012 and 2015 were evaluated. Data were collected from all centers in the Netherlands comprising demographic features, criteria for starting treatment, GETE, FEV1, oral corticosteroid use and ACQ.65.5% of the 403 patients had a good or excellent response to omalizumab after 16 weeks according to the treating physician GETE. 64.5% fulfilled all the criteria for prescribing omalizumab at baseline. The mean ACQ improved from 2.96 at baseline to 1.83 at 16 weeks (p < 0.001). 75.3% of the responders showed more than 0.5 points improvement in the ACQ. The mean FEV1 increased from 71.58 to 79.06 (p < 0.001). There was no relationship between patients with a FEV1 <80 and ≥80% at baseline and response (p = 0.981). Most of the responders had a considerable improvement of FEV1 either/or ACQ or OCS use (88.3%). While 86.7% of the responders had an improvement of either ACQ or FEV1. 75.4% of the responders had an improvement of ACQ, while 50.4% had an improvement of FEV1. Finally 11.7% of the patients with no improvement of FEV1, ACQ or OCS use were considered to have a good response.This registry of 403 inadequately controlled severe allergic asthma patients in the Netherlands showed a good or excellent response of 65.5% to omalizumab after 16 weeks, in accordance with previous studies. The assumption that careful registration would lead to higher response rates could not be supported by the data from this registry. Improvement of ACQ appears to be a useful additional assessment tool to measure response in omalizumab treated patients.

Project description:BACKGROUND:Oxytocin is an effective drug for induction of labour, but is associated with serious adverse effects of which uterine tachysystole, fetal distress and the need of immediate delivery are the most common. Discontinuation of oxytocin once the active phase of labour is established could reduce the adverse effects. The objective is to investigate how the caesarean section rate is affected when oxytocin stimulation is discontinued in the active phase of labour compared to labours where oxytocin is continued. METHODS:CONDISOX is a double-blind multicentre randomised controlled trial conducted at Danish and Dutch Departments of Obstetrics and Gynaecology. The first participant was recruited on April 8 2016. Based on a clinically relevant relative reduction in caesarean section rate of 7%, an alpha of 0.05, a beta of 80%, we aim for 1200 participating women (600 in each arm). The CONDISOX trial includes women at a gestational age of 37-42 complete weeks of pregnancy, who have uterine activity stimulated with oxytocin infusion for the induction of labour. Women are randomised when the active phase of labour becomes established, to study medication containing either oxytocin (continuous group) or placebo (discontinued group) infusion. Women are stratified by birth site, indication for oxytocin stimulation (induction of labour, prelabour rupture of membranes) and parity (nulliparous, parous +/- previous caesarean section). We will compare the primary outcome, caesarean section rate, in the two groups using a chi-square test with a p-value of 0.05. If superiority is not demonstrated, we have a pre-defined post hoc non-inferiority boundary (margin, delta) at 1.09. Secondary outcomes include duration of the active phase of labour, incidence of uterine tachysystole, postpartum haemorrhage, admission to the neonatal intensive care unit, Apgar score, umbilical arterial blood pH, and birth experience. DISCUSSION:The high frequency of oxytocin use and the potential risks of both maternal and fetal adverse effects of oxytocin emphasise the need to determine the optimal oxytocin regime for induction of labour. TRIAL REGISTRATION:NCT02553226 (registered September 17, 2015). Eudra-CT number: 2015-002942-30.

Dataset Information

A Phase 2 Randomized Controlled Multisite Study Using Omalizumab-facilitated Rapid Desensitization to Test Continued vs Discontinued Dosing in Multifood Allergic Individuals.

Publications

A Phase 2 Randomized Controlled Multisite Study Using Omalizumab-facilitated Rapid Desensitization to Test Continued <i>vs</i> Discontinued Dosing in Multifood Allergic Individuals.

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