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Harris J.M.,Genentech | Maciuca R.,Genentech | Bradley M.S.,Genentech | Cabanski C.R.,Genentech | And 14 more authors.
Respiratory Research | Year: 2016

Background: Quilizumab, a humanized IgG1 monoclonal antibody, targets the M1-prime segment of membrane-expressed IgE, leading to depletion of IgE-switched and memory B cells. In patients with mild asthma, quilizumab reduced serum IgE and attenuated the early and late asthmatic reaction following whole lung allergen challenge. This study evaluated the efficacy and safety of quilizumab in adults with allergic asthma, inadequately controlled despite high-dose inhaled corticosteroids (ICS) and a second controller. Methods: Five hundred seventy-eight patients were randomized to monthly or quarterly dosing regimens of subcutaneous quilizumab or placebo for 36weeks, with a 48-week safety follow-up. Quilizumab was evaluated for effects on the rate of asthma exacerbations, lung function, patient symptoms, serum IgE, and pharmacokinetics. Exploratory analyses were conducted on biomarker subgroups (periostin, blood eosinophils, serum IgE, and exhaled nitric oxide). Results: Quilizumab was well tolerated and reduced serum total and allergen-specific IgE by 30-40%, but had no impact on asthma exacerbations, lung function, or patient-reported symptom measures. At Week 36, the 300mg monthly quilizumab group showed a 19.6% reduction (p=0.38) in the asthma exacerbation rate relative to placebo, but this was neither statistically nor clinically significant. Biomarker subgroups did not reveal meaningful efficacy benefits following quilizumab treatment. Conclusions: Quilizumab had an acceptable safety profile and reduced serum IgE. However, targeting the IgE pathway via depletion of IgE-switched and memory B cells was not sufficient for a clinically meaningful benefit for adults with allergic asthma uncontrolled by standard therapy. Trial registration: ClinicalTrials.gov NCT01582503 © 2016 Harris et al. Source


Wasserman R.L.,Dallas Allergy Immunology | Levy R.J.,Family Allergy and Asthma Center | Bewtra A.K.,Creighton University | Schneider L.,Childrens Hospital | And 4 more authors.
Journal of Clinical Immunology | Year: 2010

Introduction:Hereditary angioedema (HAE) is a rare disorder characterized by C1 esterase inhibitor (C1-INH) deficiency, resulting in periodic attacks of acute edema that can be life-threatening if they occur in the laryngeal region. We assessed the efficacy of C1-INH concentrate in the emergency treatment of rarely occurring acute laryngeal HAE attacks in a prospective, open-label clinical study. Methods Acute laryngeal attacks were each treated with C1-INH concentrate (Berinert) at a single dose of 20 U/kg body weight. Efficacy endpoints included time to onset of symptom relief and time to complete resolution of all symptoms, each based on the patient's assessment. Results All 39 laryngeal attacks in 16 patients were treated successfully. The median time to onset of symptom relief was 15 min. The median time to complete resolution of all symptoms was 8.25 h. No treatment-related serious adverse events occurred, and the treatment was well tolerated. The administration of C1-INH concentrate was not associated with any viral infections. Conclusion C1-INH concentrate is an effective and safe emergency treatment for providing reliable and rapid relief from the potentially life-threatening symptoms of laryngeal HAE attacks. © The Author(s) 2010. This article is published with open access at Springerlink.com. Source


Craig T.J.,Pennsylvania State University | Bewtra A.K.,Creighton University | Bahna S.L.,Louisiana State University Health Sciences Center | Hurewitz D.,Allergy Clinic of Tulsa Inc. | And 13 more authors.
Allergy: European Journal of Allergy and Clinical Immunology | Year: 2011

Background: The placebo-controlled study International Multicentre Prospective Angioedema C1-INH Trial 1 (I.M.P.A.C.T.1) demonstrated that 20 U/kg C1 esterase inhibitor (C1-INH) concentrate (Berinert®; CSL Behring, Marburg, Germany) is effective in treating acute abdominal and facial Hereditary Angioedema (HAE) attacks. Methods: I.M.PA.CT.2 was an open-label extension study of I.M.P.A.C.T.1 to evaluate the safety and efficacy of long-term treatment with 20 U/kg C1-INH for successive HAE attacks at any body location. Efficacy outcomes included patient-reported time to onset of symptom relief (primary) and time to complete resolution of all symptoms (secondary), analysed on a per-patient and per-attack basis. Safety assessments included adverse events, vital signs, viral safety and anti-C1-INH antibodies. Results: During a median study duration of 24 months, 1085 attacks were treated in 57 patients (10-53 years of age). In the per-patient analysis, the median time to onset of symptom relief was 0.46 h and was similar for all types of attacks (0.39-0.48 h); the median time to complete resolution of symptoms was 15.5 h (shortest for laryngeal attacks: 5.8 h; 12.8-26.6 h for abdominal, peripheral and facial attacks). Demographic factors, type of HAE, intensity of attacks, time to treatment, use of androgens and presence of anti-C1-INH antibodies had no clinically relevant effect on the efficacy outcomes. There were no treatment-related safety concerns. No inhibitory anti-C1-INH antibodies were detected in any patient. Conclusions: A single dose of 20 U/kg C1-INH concentrate is safe and provides reliable efficacy in the long-term treatment of successive HAE attacks at any body location. © 2011 John Wiley & Sons A/S. Source


Craig T.J.,Pennsylvania State University | Bewtra A.K.,Creighton University | Hurewitz D.,Allergy Clinic of Tulsa Inc. | Levy R.,Family Allergy and Asthma Center | And 8 more authors.
Allergy and Asthma Proceedings | Year: 2012

Placebo-controlled studies established the efficacy of replacement therapy with C1 esterase inhibitor (C1-INH) concentrate for treating single acute hereditary angioedema (HAE) attacks, but only limited data from prospective studies are available on repeated treatment of successive HAE attacks. This study evaluates the association between repeated treatments with 20 U/kg of C1-INH concentrate (Berinert; CSL Behring, Marburg, Germany) for HAE attacks at any body location and treatment response. In a post hoc analysis of an open-label extension study (International Multicenter Prospective Angioedema C1-INH Trial [I.M.P.A.C.T.2]), the association between repeated treatment with C1-INH and times to onset of symptom relief and complete resolution of HAE symptoms was assessed in patients who were treated for at least 15 attacks by linear regression on the ordinal attack number. Eighteen patients received C1-INH concentrate for at least 15 HAE attacks over a mean duration of 34 months. Demographic and baseline characteristics of these patients were similar to those of all patients in the study. The distribution of body locations and the intensity of HAE attacks were similar for each of the first 15 attacks and subsequent attacks. The extent of previous use of C1-INH concentrate had no effect on the time to onset of symptom relief, the time to complete resolution of HAE symptoms, or the time between attacks treated with C1-INH concentrate; the median of individual linear regression coefficients was not statistically significantly different from 0. Treatment with 20 U/kg of C1-INH concentrate provided consistent treatment response in patients treated for multiple successive HAE attacks at any body location. (Clinicaltrials.gov identifier: NCT00292981). Copyright © 2012, OceanSide Publications, Inc. Source


Choudhury S.R.,Amity University | Chanda S.,Allergy and Asthma Research Center | Pathak A.N.,Amity University | Das S.,Christian Medical College
Current Diabetes Reviews | Year: 2014

Population explosion, urbanization, changes in lifestyle management, improper food habits and various other factors play focal contributors in the massive prevalence of type 2 diabetes mellitus in the developing countries. Although insulin is the cornerstone in the management of type 1 diabetes; insulin, anti-hyperglycemic and hypoglycemic agents are proved to be effective in type 2 diabetes, although their efficacy decreases with the progress of the disease. Moreover a significant number of side effects, mostly hypoglycemia and weight gain have put a bar in using these drugs confidently. Many novel therapeutic strategies with convincing efficacy and less adverse effects are currently emerging for providing efficient means of treatment of this disorder. This article mainly focuses on newer and unconventional pharmaceutical or biotechnical strategies that may or may not have been implied for the treatment of Type 2 Diabetes mellitus on a widescale basis so far. These strategies are supposed to be efficient in controlling glycemic levels and possess a significant potential to reduce the co-morbidities associated with this disease. © 2014 Bentham Science Publishers. Source

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