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Nurmatov U, Dhami S, Arasi S, et al., 2017, Allergen immunotherapy for allergic rhinoconjunctivitis: a systematic overview of systematic reviews, CLINICAL AND TRANSLATIONAL ALLERGY, Vol: 7, ISSN: 2045-7022
BackgroundThe European Academy of Allergy and Clinical Immunology (EAACI) is developing Guidelines on Allergen Immunotherapy (AIT) for Allergic Rhinoconjunctivitis (ARC). To inform the development of recommendations, we sought to critically assess the systematic review evidence on the effectiveness, safety and cost-effectiveness of AIT for ARC.MethodsWe undertook a systematic overview, which involved searching nine international biomedical databases from inception to October 31, 2015. Studies were independently screened by two reviewers against pre-defined eligibility criteria and critically appraised using the Critical Appraisal Skills Programme (CASP) Systematic Review Checklist for systematic reviews. Data were descriptively synthesized.ResultsOur searches yielded a total of 5932 potentially eligible studies, from which 17 systematic reviews met our inclusion criteria. Eight of these were judged to be of high, five moderate and three low quality. These reviews suggested that, in carefully selected patients, subcutaneous (SCIT) and sublingual (SLIT) immunotherapy resulted in significant reductions in symptom scores and medication requirements. Serious adverse outcomes were rare for both SCIT and SLIT. Two systematic reviews reported some evidence of potential cost savings associated with use of SCIT and SLIT.ConclusionsWe found moderate-to-strong evidence that SCIT and SLIT can, in appropriately selected patients, reduce symptoms and medication requirements in patients with ARC with reassuring safety data. This evidence does however need to be interpreted with caution, particularly given the heterogeneity in the populations, allergens and protocols studied. There is a lack of data on the relative effectiveness, cost-effectiveness and safety of SCIT and SLIT. We are now systematically reviewing all the primary studies, including recent evidence that has not been incorporated into the published systematic reviews.
Shamji MH, Mosges R, Bonny M, et al., 2017, Short course treatment of subcutaneous peptide hydrolysate from lolium perenne (LPP) suppresses basophil responses and induces igg-associated blocking antibodies: a RDPCT, Congress of the European-Academy-of-Allergy-and-Clinical-Immunology, Publisher: WILEY, Pages: 143-143, ISSN: 0105-4538
Eifan AO, Orban N, Hwang W, et al., 2017, Increased expression of SMAD7 in persistent allergic rhinitis, Congress of the European-Academy-of-Allergy-and-Clinical-Immunology, Publisher: WILEY, Pages: 85-85, ISSN: 0105-4538
Durham S, Schwabe C, Robson R, et al., 2017, A randomized clinical trial of passive immunotherapy with single-dose anti-Fel d1 monoclonal antibodies REGN 1908-1909 in cat-induced rhinoconjunctivitis: exploratory efficacy endpoints, safety, and, Congress of the European-Academy-of-Allergy-and-Clinical-Immunology, Publisher: WILEY, Pages: 64-65, ISSN: 0105-4538
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Moesges R, Panzner P, Pfaar O, et al., 2017, Efficacy of a 3-week subcutaneous immunotherapy course in patients with grass pollen-induced rhinoconjunctivitis: Results of a phase-3 study, Congress of the European-Academy-of-Allergy-and-Clinical-Immunology, Publisher: WILEY, Pages: 374-374, ISSN: 0105-4538
Bachert C, Sousa AR, Lund VJ, et al., 2017, Reduced need for surgery in severe nasal polyposis with mepolizumab: Randomized trial, Journal of Allergy and Clinical Immunology, Vol: 140, Pages: 1024-1031.e14, ISSN: 0091-6749
BackgroundPatients with eosinophilic nasal polyposis frequently require surgery, and recurrence rates are high.ObjectiveWe sought to assess the efficacy and safety of mepolizumab versus placebo for severe bilateral nasal polyposis.MethodsThis randomized, double-blind, placebo-controlled trial recruited patients aged 18 to 70 years with recurrent nasal polyposis requiring surgery. Patients received 750 mg of intravenous mepolizumab or placebo every 4 weeks for a total of 6 doses in addition to daily topical corticosteroid treatment. The primary end point was the number of patients no longer requiring surgery at Week 25 based on a composite end point of endoscopic nasal polyp score and nasal polyposis severity visual analog scale (VAS) score. Secondary end points included change in nasal polyposis severity VAS score, endoscopic nasal polyp score, improvement in individual VAS symptoms (rhinorrhea, mucus in throat, nasal blockage, and sense of smell), patient-reported outcomes, and safety.ResultsOne hundred five patients received mepolizumab (n = 54) or placebo (n = 51). A significantly greater proportion of patients in the mepolizumab group compared with the placebo group no longer required surgery at Week 25 (16 [30%] vs 5 [10%], respectively; P = .006). There was a significant improvement in nasal polyposis severity VAS score, endoscopic nasal polyp score, all individual VAS symptom scores, and Sino-Nasal Outcome Test patient-reported outcome score in the mepolizumab compared with placebo groups. Mepolizumab's safety profile was comparable with that of placebo.ConclusionIn patients with recurrent nasal polyposis receiving topical corticosteroids who required surgery, mepolizumab treatment led to a greater reduction in the need for surgery and a greater improvement in symptoms than placebo.
Scadding GK, Kariyawasam HH, Scadding G, et al., 2017, BSACI guideline for the diagnosis and management of allergic and non-allergic rhinitis (Revised Edition 2017; First edition 2007), CLINICAL AND EXPERIMENTAL ALLERGY, Vol: 47, Pages: 856-889, ISSN: 0954-7894
Hoffmann HJ, Valovirta E, Pfaar O, et al., 2017, Novel approaches and perspectives in allergen immunotherapy, ALLERGY, Vol: 72, Pages: 1022-1034, ISSN: 0105-4538
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- Citations: 56
Dhami S, Nurmatov U, Arasi S, et al., 2017, Allergen immunotherapy for allergic rhinoconjunctivitis: A systematic review and meta-analysis., Allergy, Vol: 72, Pages: 1597-1631
BACKGROUND: The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing Guidelines on Allergen Immunotherapy (AIT) for Allergic Rhinoconjunctivitis. To inform the development of clinical recommendations, we undertook a systematic review to assess the effectiveness, cost-effectiveness, and safety of AIT in the management of allergic rhinoconjunctivitis. METHODS: We searched nine international biomedical databases for published, in-progress, and unpublished evidence. Studies were independently screened by two reviewers against predefined eligibility criteria and critically appraised using established instruments. Our primary outcomes of interest were symptom, medication, and combined symptom and medication scores. Secondary outcomes of interest included cost-effectiveness and safety. Data were descriptively summarized and then quantitatively synthesized using random-effects meta-analyses. RESULTS: We identified 5960 studies of which 160 studies satisfied our eligibility criteria. There was a substantial body of evidence demonstrating significant reductions in standardized mean differences (SMD) of symptom (SMD -0.53, 95% CI -0.63, -0.42), medication (SMD -0.37, 95% CI -0.49, -0.26), and combined symptom and medication (SMD -0.49, 95% CI -0.69, -0.30) scores while on treatment that were robust to prespecified sensitivity analyses. There was in comparison a more modest body of evidence on effectiveness post-discontinuation of AIT, suggesting a benefit in relation to symptom scores. CONCLUSIONS: AIT is effective in improving symptom, medication, and combined symptom and medication scores in patients with allergic rhinoconjunctivitis while on treatment, and there is some evidence suggesting that these benefits are maintained in relation to symptom scores after discontinuation of therapy.
Makatsori M, Durham S, Calderon MA, 2017, Specific immunotherapy for latex allergy, Cochrane Database of Systematic Reviews, Vol: 2017
© 2017 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To evaluate the efficacy of subcutaneous and sublingual immunotherapy for type I latex allergy in reducing allergen sensitivity following latex exposure. To evaluate the safety of subcutaneous and sublingual immunotherapy for type I latex allergy.
Nelson HS, Calderon MA, Bernstein DI, et al., 2017, Allergen Immunotherapy Clinical Trial Outcomes and Design: Working Toward Harmonization of Methods and Principles, CURRENT ALLERGY AND ASTHMA REPORTS, Vol: 17, ISSN: 1529-7322
Scadding GW, Calderon MA, Shamji MH, et al., 2017, Effect of 2 years of treatment with sublingual grass pollen immunotherapy on nasal response to allergen challenge at three years among patients with moderate to severe seasonal allergic rhinitis: The GRASS randomized clinical trial, Journal of the American Medical Association, Vol: 317, Pages: 615-625, ISSN: 0098-7484
Importance Sublingual immunotherapy and subcutaneous immunotherapy are effective in seasonal allergic rhinitis. Three years of continuous treatment with subcutaneous immunotherapy and sublingual immunotherapy has been shown to improve symptoms for at least 2 years following discontinuation of treatment.Objective To assess whether 2 years of treatment with grass pollen sublingual immunotherapy, compared with placebo, provides improved nasal response to allergen challenge at 3-year follow-up.Design, Setting, and Participants A randomized double-blind, placebo-controlled, 3–parallel-group study performed in a single academic center, Imperial College London, of adult patients with moderate to severe seasonal allergic rhinitis (interfering with usual daily activities or sleep). First enrollment was March 2011, last follow-up was February 2015.Interventions Thirty-six participants received 2 years of sublingual immunotherapy (daily tablets containing 15 µg of major allergen Phleum p 5 and monthly placebo injections), 36 received subcutaneous immunotherapy (monthly injections containing 20 µg of Phleum p 5 and daily placebo tablets) and 34 received matched double-placebo. Nasal allergen challenge was performed before treatment, at 1 and 2 years of treatment, and at 3 years (1 year after treatment discontinuation).Main Outcomes and Measures Total nasal symptom scores (TNSS; range; 0 [best] to 12 [worst]) were recorded between 0 and 10 hours after challenge. The minimum clinically important difference for change in TNSS within an individual is 1.08. The primary outcome was TNSS comparing sublingual immunotherapy vs placebo at year 3. Subcutaneous immunotherapy was included as a positive control. The study was not powered to compare sublingual immunotherapy with subcutaneous immunotherapy.Results Among 106 randomized participants (mean age, 33.5 years; 34 women [32.1%]), 92 completed the study at 3 years. In the intent-to-treat population, mean TNSS sc
Shamji MH, Kappen JH, Akdis M, et al., 2017, Biomarkers for monitoring clinical efficacy of allergen immunotherapy for allergic rhinoconjunctivitis and allergic asthma: an EAACI Position Paper, ALLERGY, Vol: 72, Pages: 1156-1173, ISSN: 0105-4538
Scadding G, Eifan AO, Calderon MA, et al., 2017, Response to Nasal Challenge Correlates with Seasonal Outcomes during Grass Pollen Immunotherapy with Either Subcutaneous or Sublingual Immunotherapy, Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI), Publisher: MOSBY-ELSEVIER, Pages: AB385-AB385, ISSN: 0091-6749
Singh I, Qaseem A, Pathan A, et al., 2017, Surfactant Protein-D (SP-D): a Potential Therapeutic Target for Seasonal Allergic Rhinitis, Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI), Publisher: MOSBY-ELSEVIER, Pages: AB84-AB84, ISSN: 0091-6749
van Dijck AF, Kousar L, Layhadi J, et al., 2017, SATB1 is repressed in FoxP3+Tregs following Grass Pollen Subcutaneous and Sublingual Immunotherapy and Correlates with Clinical efficacy, Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI), Publisher: MOSBY-ELSEVIER, Pages: AB192-AB192, ISSN: 0091-6749
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Nelson HS, Durham SR, 2017, Allergen Immunotherapy for a Teenager with Seasonal Allergic Rhinitis Due to Grass Pollen: Subcutaneous or Sublingual Route?, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE, Vol: 5, Pages: 52-57, ISSN: 2213-2198
Bousquet J, Hellings PW, Agache I, et al., 2016, ARIA 2016: Care pathways implementing emerging technologies for predictive medicine in rhinitis and asthma across the life cycle, Clinical and Translational Allergy, Vol: 6, ISSN: 2045-7022
The Allergic Rhinitis and its Impact on Asthma (ARIA) initiative commenced during a World Health Organization workshop in 1999. The initial goals were (1) to propose a new allergic rhinitis classification, (2) to promote the concept of multi-morbidity in asthma and rhinitis and (3) to develop guidelines with all stakeholders that could be used globally for all countries and populations. ARIA—disseminated and implemented in over 70 countries globally—is now focusing on the implementation of emerging technologies for individualized and predictive medicine. MASK [MACVIA (Contre les Maladies Chroniques pour un Vieillissement Actif)-ARIA Sentinel NetworK] uses mobile technology to develop care pathways for the management of rhinitis and asthma by a multi-disciplinary group and by patients themselves. An app (Android and iOS) is available in 20 countries and 15 languages. It uses a visual analogue scale to assess symptom control and work productivity as well as a clinical decision support system. It is associated with an inter-operable tablet for physicians and other health care professionals. The scaling up strategy uses the recommendations of the European Innovation Partnership on Active and Healthy Ageing. The aim of the novel ARIA approach is to provide an active and healthy life to rhinitis sufferers, whatever their age, sex or socio-economic status, in order to reduce health and social inequalities incurred by the disease.
Singh I, Qaseem AS, Pathan AA, et al., 2016, Surfactant protein D (SP-D): a novel therapeutic target for suppressing grass pollen-induced Th2 and B responses in seasonal allergic rhinitis, Annual Meeting of the British-Society-for-Allergy-and-Clinical-Immunology (BSACI), Publisher: WILEY-BLACKWELL, Pages: 1630-1630, ISSN: 0954-7894
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- Citations: 1
Pillai P, Chan Y-C, Wu S-Y, et al., 2016, Omalizumab reduces bronchial mucosal IgE and improves lung function in non-atopic asthma, EUROPEAN RESPIRATORY JOURNAL, Vol: 48, Pages: 1593-1601, ISSN: 0903-1936
Calderon MA, Demoly P, Casale T, et al., 2016, Allergy immunotherapy across the life cycle to promote active and healthy ageing: from research to policies, Clinical and Translational Allergy, Vol: 6, ISSN: 2045-7022
Allergic diseases often occur early in life and persist throughout life. This life-course perspective should be considered in allergen immunotherapy. In particular it is essential to understand whether this al treatment may be used in old age adults. The current paper was developed by a working group of AIRWAYS integrated care pathways for airways diseases, the model of chronic respiratory diseases of the European Innovation Partnership on active and healthy ageing (DG CONNECT and DG Santé). It considered (1) the political background, (2) the rationale for allergen immunotherapy across the life cycle, (3) the unmet needs for the treatment, in particular in preschool children and old age adults, (4) the strategic framework and the practical approach to synergize current initiatives in allergen immunotherapy, its mechanisms and the concept of active and healthy ageing.
Pfaar O, Bastl K, Berger U, et al., 2016, Defining pollen exposure times for clinical trials of allergen immunotherapy for pollen-induced rhinoconjunctivitis - an EAACI position paper, ALLERGY, Vol: 72, Pages: 713-722, ISSN: 0105-4538
Slovick A, Douiri A, Muir R, et al., 2016, Intradermal grass pollen immunotherapy increases T(H)2 and IgE responses and worsens respiratory allergic symptoms, Journal of Allergy and Clinical Immunology, Vol: 139, Pages: 1830-1839.e13, ISSN: 0091-6749
BackgroundRepeated low-dose grass pollen intradermal allergen injection suppresses allergen-induced cutaneous late-phase responses comparably with conventional subcutaneous and sublingual immunotherapy.ObjectiveWe sought to evaluate the efficacy and safety of grass pollen intradermal immunotherapy in the treatment of allergic rhinitis.MethodsWe randomly assigned 93 adults with grass pollen–induced allergic rhinitis to receive 7 preseasonal intradermal allergen injections (containing 7 ng of Phl p 5 major allergen) or a histamine control. The primary end point was daily combined symptom-medication scores during the 2013 pollen season (area under the curve). Analysis was by intention to treat. Skin biopsy specimens were collected after intradermal allergen challenges, and late-phase responses were measured 4 and 7, 10, or 13 months after treatment.ResultsThere was no significant difference in the primary end point between treatment arms (active, n = 46; control, n = 47; median difference, 14; 95% CI, −172.5 to 215.1; P = .80). Among secondary end points, nasal symptoms were worse in the intradermal treatment group, as measured based on daily (median difference, 35; 95% CI, 4.0-67.5; P = .03) and visual analog scale (median difference, 53; 95% CI, −11.6 to 125.2; P = .05) scores. In a per-protocol analysis intradermal immunotherapy was further associated with worse asthma symptoms and fewer symptom-free days. Intradermal immunotherapy increased serum Phleum pratense–specific IgE levels (P = .001) compared with those in the control arm. T cells cultured from biopsy specimens of subjects undergoing intradermal immunotherapy had higher expression of the TH2 surface marker CRTH2 (P = .04) and lower expression of the TH1 marker CXCR3 (P = .01), respectively. Late-phase responses remained inhibited 7 months after treatment (P = .03).ConclusionIntradermal allergen immunotherapy suppressed skin late-phase responses but was not clinically effective and r
Kappen JH, Durham SR, Veen HI, et al., 2016, Applications and mechanisms of immunotherapy in allergic rhinitis and asthma., Therapeutic Advances in Respiratory Disease, Vol: 11, Pages: 73-86, ISSN: 1753-4658
Clinical and immunologic tolerance are hallmarks of successful allergen immunotherapy (AIT). Clinical benefits such as reduced symptoms, pharmacotherapy intake and improvement of quality of life persist following cessation of treatment. Successful AIT is associated with suppression of allergic inflammatory cells such as mast cells, eosinophils and basophils in target organs. Furthermore, AIT down-regulates type 2 innate lymphoid cells and allergen-specific type 2 T-helper (Th2) cells. The immunologic tolerant state following AIT is associated with the induction of distinct phenotypes of regulatory T-cells (T-regs) including interleukin (IL)-10-, IL-35- and transforming growth factor (TGF)-β- producing T-regs and FoxP3(+) T-regs. B-cell responses, including the induction of IL-10(+) regulatory B-cells (B-regs) and the production of IgG4-associated blocking antibodies are also induced following successful AIT. These events are associated with the suppression of antigen-specific Th2 responses and delayed immune deviation in favour of Th1 type responses. Insight into the mechanisms of AIT has allowed identification of novel biomarkers with potential to predict the clinical response to AIT and also novel therapeutic strategies for more effective and safer AIT.
Eifan AO, Durham SR, 2016, Pathogenesis of Rhinitis, Clinical and Experimental Allergy, Vol: 46, Pages: 1139-1151, ISSN: 1365-2222
Rhinitis is a heterogeneous condition that has been associated with inflammatory responses asin allergic rhinitis but can also occur in the absence of inflammation such as in so-called‘idiopathic’ (previously ‘vasomotor’) rhinitis. Allergic rhinitis affects approximately 1 in 4 ofthe population of westernised countries and is characterized by typical symptoms of nasalitching, sneezing, watery discharge and congestion. The intention of this review is toillustrate key concepts of the pathogenesis of rhinitis. Imbalance in innate and adaptiveimmunity together with environmental factors is likely to play major roles. In allergic rhinitis,initial allergen exposure and sensitization involves antigen presenting cells, T and Blymphocytes and results in the generation of allergen-specific T cells and allergen specificIgE antibodies. On re-exposure to relevant allergens crosslinking of IgE on mast cells resultsin the release of mediators of hypersensitivity such as histamine and immediate nasalsymptoms. Within hours, there is an infiltration by inflammatory cells, particularly Th2 Tlymphocytes, eosinophils and basophils into nasal mucosal tissue that results in the late-phaseallergic response. Evidence for nasal priming and whether or not remodelling may be afeature of allergic rhinitis will be reviewed. The occurrence of so-called ‘local’ allergicrhinitis in the absence of systemic IgE will be discussed. Non-allergic (non-IgE mediated)rhinitis will be considered in the context of inflammatory and non-inflammatory disorders.
Slovick A, Douiri A, Muir R, et al., 2016, Pollen low dose intradermal therapy evaluation (PollenLITE): a double-blind randomised placebo-controlled trial of low-dose intradermal grass pollen immunotherapy in seasonal allergic rhinitis, Meeting of the European-Academy-of-Allergy-and-Clinical-Immunology, Publisher: WILEY-BLACKWELL, Pages: 60-60, ISSN: 0105-4538
Zadoyan G, Allekotte S, Shamji MH, et al., 2016, Immunological biomarker predict clinical effects in subcutaneous peptide allergen immunotherapy, Meeting of the European-Academy-of-Allergy-and-Clinical-Immunology, Publisher: WILEY-BLACKWELL, Pages: 319-320, ISSN: 0105-4538
Steveling-Klein EH, Lao-Araya M, Koulias C, et al., 2016, A randomised placebo-controlled trial of sublingual immunotherapy tablet for seasonal rhinitis to grass allergen: clinical outcomes, local symptoms and early time course of immunologic changes, Meeting of the European-Academy-of-Allergy-and-Clinical-Immunology, Publisher: WILEY-BLACKWELL, Pages: 616-616, ISSN: 0105-4538
Kappen J, Schmidt-Weber C, Akdis M, et al., 2016, Evaluation of novel and current biomarkers for monitoring clinical efficacy of allergen immunotherapy for allergic rhinoconjunctivitis and allergic asthma, Meeting of the European-Academy-of-Allergy-and-Clinical-Immunology, Publisher: WILEY-BLACKWELL, Pages: 455-455, ISSN: 0105-4538
Creticos PS, Durham S, Nelson HS, et al., 2016, Comparison of relative and absolute treatment differences between sublingual immunotherapy tablets and pharmacotherapies for seasonal and perennial allergic rhinitis: pooled analyses of clinical trials, Meeting of the European-Academy-of-Allergy-and-Clinical-Immunology, Publisher: WILEY-BLACKWELL, Pages: 29-29, ISSN: 0105-4538
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