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Margitta Worm - One of the best experts on this subject based on the ideXlab platform.
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dose response relationship of a new timothy grass pollen Allergoid in comparison with a 6 grass pollen Allergoid
Clinical & Experimental Allergy, 2017Co-Authors: Oliver Pfaar, B. Hauswald, P. Velling, Nico Hunzelmann, Bernhard Homey, Sibylle Schliemann, Jens M. Hohlfeld, B Alkadah, Margitta WormAbstract:Background Subcutaneous allergen immunotherapy with grass pollen Allergoids has been proven to be effective and safe in the treatment of patients with allergic rhinoconjunctivitis. Based on the extensive cross-reactivity among Pooideae species, it has been suggested that grass pollen extracts could be prepared from a single species, rather than from a multiple species mixture. Objective To find the optimal dose of a Phleum pratense Allergoid preparation and compare its efficacy and safety to a 6-grass pollen Allergoid preparation. Methods In this double-blind, placebo-controlled study (EudraCT: 2011-000674-58), 3 doses of Phleum pratense Allergoid (1800 Therapeutic Units (TU), standard dose 6000 TU, and 18000 TU) were compared with placebo and the marketed 6-grass pollen Allergoid (6000 TU). In a preseasonal dosing regimen, 102 patients were randomized to 5 treatment groups and received 9 subcutaneous injections. The primary efficacy endpoint was the change in wheal size (late phase reaction, LPR) in response to the intracutaneous testing (ICT) before and after treatment, comparing the active Allergoids to placebo. Secondary outcomes were the change in Total Nasal Symptom Score (TNSS) assessed in the allergen exposure chamber (AEC), the changes in Phleum pratense-serum specific IgG4, and the incidence of adverse events (AEs). Results All 3 doses of the Phleum pratense and the 6-grass pollen Allergoid preparations were significantly superior to placebo for the primary outcome, whereas there were no significant differences in the change in TNSS. Compared to the standard dose, the high dose of Phleum pratense did not produce any additional significant benefit, but showed a slight increase in AEs. Yet this increase in AEs was lower than for the 6-grass pollen preparation. Conclusions & Clinical Relevance The standard dose of the new Phleum pratense Allergoid was comparable to the marketed 6-grass pollen preparation at equal dose for the parameters measured. This article is protected by copyright. All rights reserved.
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Dose‐response relationship of a new Timothy grass pollen Allergoid in comparison with a 6‐grass pollen Allergoid
Clinical & Experimental Allergy, 2017Co-Authors: Oliver Pfaar, B. Al‐kadah, B. Hauswald, P. Velling, Nico Hunzelmann, Bernhard Homey, Sibylle Schliemann, Margitta Worm, Jens M. Hohlfeld, Ludger KlimekAbstract:Background Subcutaneous allergen immunotherapy with grass pollen Allergoids has been proven to be effective and safe in the treatment of patients with allergic rhinoconjunctivitis. Based on the extensive cross-reactivity among Pooideae species, it has been suggested that grass pollen extracts could be prepared from a single species, rather than from a multiple species mixture. Objective To find the optimal dose of a Phleum pratense Allergoid preparation and compare its efficacy and safety to a 6-grass pollen Allergoid preparation. Methods In this double-blind, placebo-controlled study (EudraCT: 2011-000674-58), 3 doses of Phleum pratense Allergoid (1800 Therapeutic Units (TU), standard dose 6000 TU, and 18000 TU) were compared with placebo and the marketed 6-grass pollen Allergoid (6000 TU). In a preseasonal dosing regimen, 102 patients were randomized to 5 treatment groups and received 9 subcutaneous injections. The primary efficacy endpoint was the change in wheal size (late phase reaction, LPR) in response to the intracutaneous testing (ICT) before and after treatment, comparing the active Allergoids to placebo. Secondary outcomes were the change in Total Nasal Symptom Score (TNSS) assessed in the allergen exposure chamber (AEC), the changes in Phleum pratense-serum specific IgG4, and the incidence of adverse events (AEs). Results All 3 doses of the Phleum pratense and the 6-grass pollen Allergoid preparations were significantly superior to placebo for the primary outcome, whereas there were no significant differences in the change in TNSS. Compared to the standard dose, the high dose of Phleum pratense did not produce any additional significant benefit, but showed a slight increase in AEs. Yet this increase in AEs was lower than for the 6-grass pollen preparation. Conclusions & Clinical Relevance The standard dose of the new Phleum pratense Allergoid was comparable to the marketed 6-grass pollen preparation at equal dose for the parameters measured. This article is protected by copyright. All rights reserved.
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the impact on allergy related cells of a birch pollen Allergoid with and without monophosphoryl lipid a in comparison with the native equivalent
International Archives of Allergy and Immunology, 2017Co-Authors: Margitta Worm, Dennis Ernst, M Kraller, M BabinaAbstract:Background: The clinical efficacy and safety of Allergoid immunotherapy have been demonstrated in clinical trials. However, simultaneous monitoring of the immunol
Giorgio Walter Canonica - One of the best experts on this subject based on the ideXlab platform.
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the clinical efficacy of a sublingual monomeric Allergoid at different maintenance doses a randomized controlled trial
International Journal of Immunopathology and Pharmacology, 2010Co-Authors: Maurizio Marogna, Paolo Falagiani, F Colombo, C Cerra, M E Bruno, Alessandro Massolo, Giorgio Walter Canonica, G PassalacquaAbstract:: Sublingual immunotherapy is widely recognized as a viable treatment for allergic rhinitis and asthma, but the optimal dosage is still under debate, especially with modified allergens. We assessed the clinical effects of a monomeric Allergoid across 3 different maintenance doses in mite-monosensitized patients with rhinitis and intermittent asthma. Eighty-nine patients allergic to HDM were randomized to 3 maintenance doses of monomeric Allergoid (Lais, Lofarma) or medications only. All the patients recorded their symptoms and rescue drug consumption in a diary card from November to February. Additionally, nasal eosinophil count, spirometry and methacholine bronchial challenge were performed at the beginning of the study and after 3 years. The symptom scores showed a clear improvement in all the three active arms versus baseline and versus the controls, irrespective of the dose. Likewise, a similar improvement versus baseline was seen for nasal inflammation and bronchial hyperreactivity. The SLIT with monomeric Allergoids produces clinically significant results across a wide range of doses. The absence of significant side effects, even at high doses, is probably due to their low level of allergeni city.
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pharmacokinetics of der p 2 allergen and derived monomeric Allergoid in allergic volunteers
International Archives of Allergy and Immunology, 2005Co-Authors: Marcello Bagnasco, Paolo Falagiani, Giorgio Walter Canonica, G Mistrello, Vania Altrinetti, Giampaola Pesce, M Caputo, Giovanni PassalacquaAbstract:BACKGROUND: Presently, sublingual immunotherapy is widely used as an alternative to the injection route for respiratory allergy, but its pharmacokinetics in humans is poorly known, and data are available only for Par j 1 allergen. We aimed at assessing the biodistribution of iodine-123-radiolabelled Der p 2 in allergic volunteers. METHODS: Purified Der p 2 and its monomeric Allergoid were radiolabelled with iodine-123 and administered sublingually to 7 allergic volunteers. The subjects were allowed to swallow 6 min after administration. Dynamic (up to 10 min) and static scintigraphic images (30 min, 1, 2, 3 and 20 h) were recorded, and blood samples were obtained at different time points to measure the plasma radioactivity and to assess the presence of circulating radiolabelled species by gel chromatography. RESULTS: The local pharmacokinetics did not differ between allergen and Allergoid. Plasma radioactivity began to increase only after swallowing and peaked at 1-2 h. Both the allergen and the Allergoid persisted in the mouth for several hours, and traces could be detectable up to 20 h. At radioactivity plasma peak, gel chromatography showed that a fraction of the Allergoid, but not the allergen, was absorbed as an intact molecule. CONCLUSIONS: These results indicate that the pharmacokinetics of sublingual administration is independent of the allergen used and characterized by the long persistence in the mouth. The contribution of enteric absorption of the Allergoid in the mechanism of action of sublingual immunotherapy remains to be defined.
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quantitative assessment of the adherence to Allergoid sublingual immunotherapy in patients with house dust mite sensitization the insit study
The Journal of Allergy and Clinical Immunology, 2004Co-Authors: Carlo Lombardi, Paolo Falagiani, G Passalacqua, F Gani, Massimo Landi, S Gargioni, Giorgio Walter CanonicaAbstract:Abstract Rationale Sublingual Immunotherapy (SLIT) is a viable alternative to conventional immunotherapy, but some concerns exist about the adherence to SLIT, and few experimental data exist about this topic. We aimed at quantifying the adherence to the SLIT in patients with mite allergy. Methods We performed a multicenter study (INSIT) to assess the adherence, given as Allergoid SLIT in tablets (Lais, Lofarma, Italy), in patients with mite allergy. Patients underwent random telephonic interviews, during which they were asked to immediately count the remaining tablets. The adherence was measured by assessing the reported number of remaining tablets versus that expected, based on the administration schedule. Demographic and socio-economic data and clinical scores were also recorded. Results Forty-one patients (16 male: 15-65 yrs, mean age: 36.3), 19 with rhino-conjunctivitis and 22 with concomitant asthma were enrolled in the first year of the study. Allergoid SLIT was given continuously and the compliance was assessed at the end of 1 year of treatment. There were two dropouts: one lack of efficacy, one onset of nasal polyps. In the remaining 39 patients, the adherence was 3.929/4.056 tablets (96.8%). Sporadically omitted doses (less than 1 tablet/month) were reported by 6 patients (14.6%). No systemic or local side-effects were reported. We also observed a statistically significant improvement of rhinoconjunctivitis and asthma symptoms score and medication consumption. The compliance was in general lower in patients frequently travelling for business reasons. Conclusions The preliminary results of this ongoing study show that the adherence to Allergoid SLIT is satisfactory, despite it is self-administered.
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pharmacokinetics of an allergen and a monomeric Allergoid for oromucosal immunotherapy in allergic volunteers
Clinical & Experimental Allergy, 2001Co-Authors: Marcello Bagnasco, Paolo Falagiani, Giovanni Mistrello, Giorgio Walter Canonica, G Passalacqua, G Villa, C Augeri, G Flamigni, E Borini, G MarianiAbstract:BACKGROUND AND OBJECTIVE: Little is known about the pharmacokinetics of allergens for local immunotherapy. Thus, we studied the pharmacokinetics in allergic volunteers of a commercial allergenic vaccine in orosoluble tablets (LAIS(R), Lofarma S.p.A). METHODS: The carbamylated monomeric Allergoid derived from Parietaria judaica major allergen (Par j 1), characterized by maintenance of the original molecular size, and the native allergen, were radiolabelled with 123I, then incorporated into the commercial soluble tablets and administered to allergic subjects. Early sequential and late static scintigraphic acquisitions were performed, and plasma radioactivity was measured at different time intervals. RESULTS: No difference in local pharmacokinetics was observed between the allergen and the Allergoid: part of the tracer was retained in the mouth for at least 2 h after swallowing. No direct absorption through the oral mucosa could be detected, as plasma radioactivity increased only after swallowing and peaked at 2 h. However, the plasma peak attained with the Allergoid in tablets was significantly higher with respect to the native allergen. Finally, some undegraded Allergoid, but not the allergen, could be constantly detected in the bloodstream at plasma peak. CONCLUSIONS: The results showed a similar behaviour of the Allergoid and the allergen in tablets as far as their local kinetics are concerned, whereas plasma peak was higher with the Allergoid than with the allergen. Therefore we conclude that the chemical modification of the allergen may affect its pharmacokinetics, by making it less susceptible to enzymatic degradation.
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long term treatment with Allergoid immunotherapy with parietaria clinical and immunologic effects in a randomized controlled trial
Allergy, 1999Co-Authors: R. Ariano, Giorgio Walter Canonica, A M Kroon, G Augeri, G PassalacquaAbstract:Background: Specific immunotherapy (SIT) is a valuable treatment for respiratory allergy, and the use of chemically modified allergens (Allergoids) has improved its safety, as testified by several studies. We evaluated the effects of a SIT course with an Allergoid extract of Parietaria pollen in a double-blind, placebo-controlled trial. Methods: The study was double-blind in the first year; then it was prolonged up to 3 years with all patients on active treatment. Clinical effectiveness, safety, skin reactivity, systemic immunologic parameters, and subjective assessment were evaluated. We also had available a self-evaluation recorded in a follow-up visit 4 years after the discontinuation of SIT. Results: A significant reduction of the symptoms plus drug intake scores during the pollen seasons was observed in the patients receiving active SIT. The placebo patients, after switching to active SIT, also showed significant clinical improvement. The clinical efficacy persisted during years 2 and 3 of treatment. After year 1, the actively treated patients reported a significant subjective improvement (frequency of symptoms, P=0.001; duration of symptoms, P=0.024; physical performance, P=0.043) compared with the placebo group. The self-evaluation by visual analog scale showed that all patients maintained a significant clinical improvement up to 4 years after discontinuing SIT (year 1: active=+31.6%, placebo=−15.7%; year 7: active=+35.8%, placebo=+31.3%). The systemic immunologic changes after active SIT paralleled those described elsewhere (IgE decreased from 22 to 9 and from 21 to 8 IU/ml; IgG4 increased from 43 to 87 and from 18 to 60 IU/ml). A significant decrease in skin reactivity to three different allergen concentrations was observed at year 3 compared with pretreatment values (P<0.05). Conclusions: The investigational SIT with Parietaria appeared to be effective and safe; a 3-year course of treatment achieved a long-lasting efficacy.
Zeynep Misirligil - One of the best experts on this subject based on the ideXlab platform.
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Short-term preseasonal immunotherapy: Is early clinical efficacy related to the basophil response?
International Archives of Allergy and Immunology, 2014Co-Authors: Şahin Kaya Özdemir, B. A. Sin, Deniz Güloʇlu, Aydan Ikincioʇullari, Zeynep Gencturk, Zeynep MisirligilAbstract:BACKGROUND: An aluminum hydroxide-adsorbed depot Allergoid preparation of six-grass pollen allergens has been developed for short-term preseasonal immunotherapy in pollinosis. However, only limited knowledge exists about its immunological and clinical effects. The aim of this study was to evaluate the basophil response, which can explain early clinical findings of short-term preseasonal Allergoid immunotherapy in allergic rhinitis.\n\nMETHODS: In a double-blind, placebo-controlled study, 31 patients allergic to grass pollens received one course of short-term preseasonal Allergoid immunotherapy or placebo. Immunogenicity was assessed by the levels of specific IgG4, IgE antibodies and an allergen-induced CD203c basophil activation test. The primary clinical end point was the combined symptom and medication score/average combined score (ACS).\n\nRESULTS: There was a 52.9% difference in ACS between the treatment and placebo groups in favor of immunotherapy (p = 0.01). Active treatment induced Phleum pratense-specific IgG4 and IgE antibodies (p < 0.05). A decrease in allergen-induced basophil activation at submaximal allergen concentrations was demonstrated at the end of immunotherapy and at the peak of the grass pollen season after immunotherapy.\n\nCONCLUSIONS: This study shows that grass pollen-allergic patients treated with one course of short-term preseasonal Allergoid immunotherapy exhibit a decrease in allergen-induced basophil activation, an increase in allergen-specific IgG4 antibodies and early clinical improvement.
E Gammeri - One of the best experts on this subject based on the ideXlab platform.
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safety and tolerability of ultra rush 20 minutes Allergoid sublingual immunotherapy in patients with allergic rhinitis and or asthma
The Journal of Allergy and Clinical Immunology, 2004Co-Authors: E GammeriAbstract:Abstract Rationale The safety of sublingual immunotherapy (SLIT) has already been demonstrated in allergic patients, but only one study evaluated the occurrence of immediate adverse reactions in allergic patients after an ultra-rush regimen of SLIT with a monomeric Allergoid (Lais, Lofarma, Milan). Aim of the present study is to confirm these preliminary data and to investigate the tolerability of the Allergoid SLIT as well. Methods Twenty patients (10M, 10F, mean age: 33 years) took part in this trials on the Allergoid ultra-rush SLIT for the treatment of IgE-mediated rhinitis and/or asthma due to House Dust Mite (n=14) or Parietaria (n=6). The build-up ultra-rush phase was done by administering increasing doses of the monomeric sublingual Allergoid every 5 minutes. The cumulative dose administered, after 20 minutes, was about 4000 A.U. Careful checks to evaluate the occurrence of any adverse event were done at the same time intervals. Results All patients tolerated the treatment very well. No adverse events were seen in any patients at any time, neither during the build-up phase nor during the first week of the maintenance treatment, performed with 2000 A.U. of the Allergoid SLIT. Conclusions Our data, show the excellent safety and tolerability profile of the ultra-rush Allergoid SLIT, even when high doses are administered through an extremely short induction phase, thus confirming the previously reported results.
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Safety and tolerability of ultra-rush (20 minutes) Allergoid sublingual immunotherapy in patients with allergic rhinitis and/or asthma☆
The Journal of Allergy and Clinical Immunology, 2004Co-Authors: E GammeriAbstract:Abstract Rationale The safety of sublingual immunotherapy (SLIT) has already been demonstrated in allergic patients, but only one study evaluated the occurrence of immediate adverse reactions in allergic patients after an ultra-rush regimen of SLIT with a monomeric Allergoid (Lais, Lofarma, Milan). Aim of the present study is to confirm these preliminary data and to investigate the tolerability of the Allergoid SLIT as well. Methods Twenty patients (10M, 10F, mean age: 33 years) took part in this trials on the Allergoid ultra-rush SLIT for the treatment of IgE-mediated rhinitis and/or asthma due to House Dust Mite (n=14) or Parietaria (n=6). The build-up ultra-rush phase was done by administering increasing doses of the monomeric sublingual Allergoid every 5 minutes. The cumulative dose administered, after 20 minutes, was about 4000 A.U. Careful checks to evaluate the occurrence of any adverse event were done at the same time intervals. Results All patients tolerated the treatment very well. No adverse events were seen in any patients at any time, neither during the build-up phase nor during the first week of the maintenance treatment, performed with 2000 A.U. of the Allergoid SLIT. Conclusions Our data, show the excellent safety and tolerability profile of the ultra-rush Allergoid SLIT, even when high doses are administered through an extremely short induction phase, thus confirming the previously reported results.
Ralph Mosges - One of the best experts on this subject based on the ideXlab platform.
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a 12 week dbpc dose finding study with sublingual monomeric Allergoid tablets in house dust mite allergic patients
Allergy, 2017Co-Authors: C Huser, Enrico Compalati, P Dieterich, J Singh, Kija Shahhosseini, Silke Allekotte, Walter Lehmacher, Ralph MosgesAbstract:Background In sublingual immunotherapy, optimal doses are a key factor for therapeutic outcomes. The aim of this study with tablets containing carbamylated monomeric house dust mite Allergoids was to determine the most effective and safe dose. Methods In this double-blind, placebo-controlled dose-finding study, 131 patients with house dust mite-induced allergic rhinoconjunctivitis were randomized to 12-week treatments with 300 UA/day, 1000 UA/day, 2000 UA/day, 3000 UA/day or placebo. Conjunctival provocation tests (CPT) were performed before, during and after treatment. The change in mean allergic severity (primary endpoint), calculated from the severity of the CPT reaction, and the proportion of patients with an improved CPT threshold (secondary endpoint) determined the treatment effect. Results The mean allergic severity decreased in all groups, including the placebo group. It was lower in all active treatment groups (300 UA/day: 0.14, 1000 UA/day: 0.15, 2000 UA/day: 0.10, 3000 UA/day: 0.15) than in the placebo group (0.30). However, this difference was not statistically significant (P < 0.1). The percentage of patients with an improved CPT threshold was higher in the active treatment groups (300 UA/day: 73.9%; 1000 UA/day: 76.0%; 2000 UA/day: 88.5%; 3000 UA/day: 76.0%) than in the placebo group (64.3%). The difference between placebo and 2000 UA/day was statistically significant (P = 0.04). In 13 (10%) exposed patients, a total of 20 treatment-related adverse events of mild severity were observed. Conclusions The 12-week daily treatment using 2000 UA/day monomeric Allergoid sublingual tablets is well tolerated and reduces the CPT reaction in house dust mite-allergic patients.
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A review of Allergoid immunotherapy: Is cat allergy a suitable target?
Immunotherapy, 2016Co-Authors: N T Nguyen, E Raskopf, Kija Shah-hosseini, G Zadoyan, Ralph MosgesAbstract:To modify the course of allergy, different types of specific allergen immunotherapy have been developed such as sublingual immunotherapy and subcutaneous immunotherapy with native allergens or subcutaneous immunotherapy with polymerized Allergoids. However, the optimal specific immunotherapy, especially for cat allergy, remains undetermined. Few studies investigating immunotherapy in cat allergy have been published, and the risk of serious adverse reactions and systemic reactions has often been an important issue. Monomeric Allergoids have lower allergenic potential while their immunogenicity remains constant, resulting in excellent safety with notable efficacy. Specific immunotherapy with monomeric Allergoids could, therefore, be of high value, especially in cat allergy as well as other types of allergy, and bring relief to a great community of patients.
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towards evidence based medicine in specific grass pollen immunotherapy
Allergy, 2010Co-Authors: Moises A Calderon, Martin Hellmich, Ralph Mosges, Pascal DemolyAbstract:To cite this article: Calderon M, Mosges R, Hellmich M, Demoly P. Towards evidence-based medicine in specific grass pollen immunotherapy. Allergy 2010; 65: 420–434. Abstract When initiating grass pollen immunotherapy for seasonal allergic rhinoconjunctivitis, specialist physicians in many European countries must choose between modalities of differing pharmaceutical and regulatory status. We applied an evidence-based medicine (EBM) approach to commercially available subcutaneous and sublingual Gramineae grass pollen immunotherapies (SCIT and SLIT) by evaluating study design, populations, pollen seasons, treatment doses and durations, efficacy, quality of life, safety and compliance. After searching MEDLINE, Embase and the Cochrane Library up until January 2009, we identified 33 randomized, double-blind, placebo-controlled trials (including seven paediatric trials) with a total of 440 specific immunotherapy (SIT)-treated subjects in seven trials (0 paediatric) for SCIT with natural pollen extracts, 168 in three trials (0 paediatric) for SCIT with Allergoids, 906 in 16 trials (five paediatric) for natural extract SLIT drops, 41 in two trials (one paediatric) for Allergoid SLIT tablets and 1605 in five trials (two paediatric) for natural extract SLIT tablets. Trial design and quality varied significantly within and between SIT modalities. The multinational, rigorous trials of natural extract SLIT tablets correspond to a high level of evidence in adult and paediatric populations. The limited amount of published data on Allergoids prevented us from judging the level of evidence for this modality.
