Allergen immunotherapy Frew, Anthony J., MD, FRCP
Journal of allergy and clinical immunology,
02/2010, Letnik:
125, Številka:
2
Journal Article
Recenzirano
Specific immunotherapy (SIT) involves the administration of allergen extracts to achieve clinical tolerance of those allergens that cause symptoms in patients with allergic conditions. Immunotherapy ...is effective in patients with mild forms of allergic disease and also in those who do not respond well to standard drug therapy. Most SIT is given by means of injection, but there is increasing interest in performing SIT through the sublingual route. SIT remains the treatment of choice for patients with systemic allergic reactions to wasp and bee stings and should be considered as an option in patients with allergic rhinitis, asthma, or both. SIT can modify the course of allergic disease by reducing the risk of new allergic sensitizations and inhibiting the development of clinical asthma in children treated for allergic rhinitis. The precise mechanisms responsible for the beneficial effects of SIT remain a matter of research and debate. An effect on regulatory T cells seems most probable and is associated with switching of allergen-specific B cells toward IgG4 production. Few direct comparisons of SIT and drug therapy have been made. Existing data suggest that the effects of SIT take longer to develop, but once established, SIT achieves long-lasting relief of allergic symptoms, whereas the benefits of drugs only last as long as they are continued.
Sublingual Immunotherapy Frew, Anthony J
The New England journal of medicine,
05/2008, Letnik:
358, Številka:
21
Journal Article
Recenzirano
A 28-year-old man presents with allergic rhinitis, primarily due to grass pollen, that has not previously responded to antihistamines and nasal sprays. A trial of sublingual immunotherapy is ...recommended. Sublingual immunotherapy is more convenient than injection immunotherapy. However, only one agent, which is specific for grass-pollen allergies, has been approved for clinical use in some European countries. The Food and Drug Administration has not approved any agent for sublingual immunotherapy.
A 28-year-old man presents with allergic rhinitis, primarily due to grass pollen. A trial of sublingual immunotherapy is recommended. Only one agent, which is specific for grass-pollen allergies, has been approved for clinical use in some European countries.
Foreword
This
Journal
feature begins with a case vignette that includes a therapeutic recommendation. A discussion of the clinical problem and the mechanism of benefit of this form of therapy follows. Major clinical studies, the clinical use of this therapy, and potential adverse effects are reviewed. Relevant formal guidelines, if they exist, are presented. The article ends with the author's clinical recommendations.
A busy 28-year-old professional consults his physician for advice on long-standing hay fever. He reports having itchy eyes and an itchy nose, lacrimation, sneezing, rhinorrhea, and nasal congestion during the summer months. In previous years, he tried various antihistamines and nasal sprays, but these treatments only had limited benefit. A friend has suggested a corticosteroid injection or allergy injections, but he is hesitant to receive corticosteroids and unable to give up the time from work to receive injections. He is evaluated by an allergist. Skin testing confirms that he is strongly sensitized to grass pollen, with modest reactions to cat dander and house-dust mites. A trial of sublingual immunotherapy is recommended.
The Clinical Problem
Allergic rhinitis is a common condition affecting about one quarter of adults in the developed world. Many patients have mild symptoms that are either ignored or managed with the occasional use of antihistamine tablets. More significant symptoms are treated with the addition of topical corticosteroid sprays. Nonetheless, a significant minority of patients with allergic rhinitis continue to have troublesome symptoms despite the regular and appropriate use of antihistamines and topical corticosteroids.
1
Although allergic rhinitis is not associated with a risk of death, the disorder can have a considerable effect on the patient's quality of life. Coexisting conditions . . .
The placebo (Latin “I will please”) effect commonly occurs in clinical trials. The psychological and physiological factors associated with patients’ expectations about a treatment's positive and ...negative effects have yet to be well characterized, although a functional prefrontal cortex and intense bidirectional communication between the central nervous system and the immune system appear to be prerequisites for a placebo effect. The use of placebo raises certain ethical issues, especially if patients in a placebo group are denied an effective treatment for a long period of time. The placebo effect appears to be relatively large (up to 77%, relative to pretreatment scores) in controlled clinical trials of allergen immunotherapy (AIT), such as the pivotal, double‐blind, placebo‐controlled (DBPC) randomized clinical trials currently required by regulatory authorities worldwide. The European Academy of Allergy and Clinical Immunology (EAACI) therefore initiated a Task Force, in order to better understand the placebo effect in AIT and its specific role in comorbidities, blinding issues, adherence, measurement time points, variability and the natural course of the disease. In this Position Paper, the EAACI Task Force highlights several important topics regarding the placebo effect in AIT such as a) regulatory aspects, b) neuroimmunological and psychological mechanisms, c) placebo effect sizes in AIT trials, d) methodological limitations in AIT trial design and e) potential solutions in future AIT trial design. In conclusion, this Position Paper aims to examine the methodological problem of placebo in AIT from different aspects and also to highlight unmet needs and possible solutions for future trials.
25. Immunotherapy of allergic disease Frew, Anthony J.
Journal of allergy and clinical immunology,
February 2003, 2003-Feb, 2003-2-00, 20030201, Letnik:
111, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Specific immunotherapy involves the administration of allergen extracts to achieve clinical tolerance of the allergens which cause symptoms in patients with allergic conditions. Immunotherapy has ...been shown to be effective in patients with mild forms of allergic disease, and also in those who do not respond well to standard drug therapy. Recent studies suggest that specific immunotherapy may also modify the course of allergic disease, by reducing the risk of developing new allergic sensitizations, and also inhibiting the development of clinical asthma in children treated for allergic rhinitis. Specific immunotherapy remains the treatment of choice for patients with systemic allergic reactions to wasp and bee stings. The precise mechanisms responsible for the beneficial effects of SIT remain a matter of research and debate. An effect on regulatory T cells seems most probable, associated with switching of allergen-specific B cells towards IgG4 production. Few direct comparisons of specific immunotherapy and drug therapy have been made. Existing data suggest that the effects of specific immunotherapy take longer to come on, but once established, specific immunotherapy will give long-lasting relief of allergic symptoms, whereas the benefits of drugs only last as long as they are continued. (J Allergy Clin Immunol 2003;111:S712-9.)
Specific immunotherapy is widely used to treat allergic rhinitis, but few large-scale clinical trials have been performed.
We sought to assess the efficacy and safety of specific immunotherapy with 2 ...doses of Alutard grass pollen in patients with moderately severe seasonal allergic rhinitis inadequately controlled with standard drug therapy.
We performed a double-blind, randomized, placebo-controlled study of 410 subjects (203 randomized to 100,000 standardized quality units SQ-U maintenance, 104 to 10,000 SQ-U, and 103 to placebo). Three hundred forty-seven (85%) completed treatment. Groups were well matched for demographics and symptoms.
Across the whole pollen season, mean symptom and medication scores were 29% and 32% lower, respectively, in the 100,000–SQ-U group compared with those in the placebo group (both
P < .001). Over the peak pollen season, mean symptom and medication scores were 32% and 41% lower, respectively, than those in the placebo group. The 10,000–SQ-U group had 22% less symptoms than the placebo group over the whole season (
P < .01), but medication scores reduced by only 16% (
P = .16). Quality-of-life measures confirmed the superiority of both doses to placebo. Local and delayed side effects were common but generally mild. Clinically significant early and delayed systemic side effects were confined to the 100,000–SQ-U group, but no life-threatening reactions occurred.
One season of immunotherapy with Alutard grass pollen reduced symptoms and medication use and improved the quality of life of subjects with moderately severe hay fever. The 100,000–SQ-U regimen was more effective, but the 10,000–SQ-U regimen caused fewer side effects.
...Di Bona et al1 performed a rigorous meta-analysis but overinterpreted the results while losing sight of other important parameters. ...the availability of AIT as a treatment option is an important ...part of evidence-based medicine and the patient-physician dialog.
Background
Our understanding of factors which affect adherence to health sustaining self‐care behaviours in adolescents with food allergy is limited. This study used the Health Belief Model to ...explore the relationship between food allergic adolescents' health beliefs, demographic, structural and social psychological factors with adherence to self‐care behaviours, including allergen avoidance and carrying emergency medication.
Methods
A cross‐sectional study of 188 13‐ to 19‐ olds identified from hospital prescribed auto‐injectable epinephrine for food allergy. Data were collected on demographics, structural factors, social psychological factors, health beliefs and current adherence behaviour using a postal questionnaire.
Results
Full adherence was reported by 16% of participants. Multivariate analysis indicated that adherence was more likely to be reported if the adolescents belonged to a support group (OR = 2.54, (1.04, 6.20) 95% CI), had an anaphylaxis management plan (OR = 3.22, (1.18, 8.81) 95% CI), perceived their food allergy to be more severe (OR = 1.24, (1.01, 1.52) 95% CI) and perceived fewer barriers to disease management (OR = 0.87, (0.79, 0.96) 95% CI).
Conclusions
Membership of a patient support group and having an anaphylaxis management plan were associated with good adherence to self‐care behaviours in adolescents with food allergy. Our results suggest that interventions to improve provision and utilisation of management plans, address adolescents' perceptions of the severity of anaphylaxis and reduce barriers to disease management may facilitate good adherence behaviours than focussing on knowledge‐based interventions.
Placebo effects are common in medicine. Randomised clinical trials help us to understand their magnitude in different therapies. There are particular problems with placebo effects in allergen ...immunotherapy (AIT) as it is difficult to blind the active treatment and the endpoints are largely subjective. This may explain why large placebo effects are often found in AIT trials. Patients receiving open label AIT get the benefit of the active and placebo components but it can be difficult to say how much benefit is due to the active component. The use of active placebos has been proposed but brings its own problems (ethical and scientific). An EAACI Task Force has been established to address these issues. Here we review the current literature on the placebo effect in general, with a special focus on AIT trials, and indicate what we believe to be important considerations and unmet needs in AIT trial design.
Specific immunotherapy is a well-established treatment for allergic rhinoconjunctivitis; conventional regimens are lengthy, however, reducing convenience and cost-effectiveness. This study evaluated ...the efficacy and safety of an ultrashort course (four doses) of the immunotherapy Grass Modified Allergen Tyrosine Adsorbate (Allergy Therapeutics, Worthing, U.K.) monophosphoryl lipid A (MATA MPL). Subjects were randomized to receive four injections of either Grass MATA MPL (n = 514; 300-2000 standardized units/injection) or placebo (n = 514) before the grass pollen season. They used electronic diaries to record allergy symptoms and medication use during the pollen season. The primary end point was the difference between the mean combined symptom and medication scores in the Grass MATA MPL and placebo groups during the 4 local peak pollen weeks. The injection course was completed by 95.3 and 97.7% of the Grass MATA MPL and placebo groups, respectively, and was well tolerated. Grass MATA MPL treatment afforded a 13.4% benefit over placebo in the 4 peak pollen weeks (p = 0.0038). The benefit in subjects with 28 complete diary entries during the 4 peak pollen weeks was 26.9% (p = 0.0031). Significant benefits over placebo were observed in subjects with severe symptoms (17.1%; p = 0.0023), in those who had a history of allergic rhinoconjunctivitis for up to 35 years (up to 37.2%; p = 0.0059) and at sites with a higher burden of disease (38.3%; p < 0.0001). The ultrashort course of Grass MATA MPL was well tolerated and provided a significant benefit over placebo in relieving allergy symptoms.
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