Subcutaneous Immunotherapy and Pharmacotherapy in Seasonal Allergic Rhinitis: A Comparison based on Meta-Analyses

Pediatric Pneumology and Immunology Department, Charité Medical University, Berlin, Germany.
The Journal of allergy and clinical immunology (Impact Factor: 11.48). 05/2011; 128(4):791-799.e6. DOI: 10.1016/j.jaci.2011.03.049
Source: PubMed


Allergen-specific subcutaneous immunotherapy (SCIT) of seasonal allergic rhinitis (SAR) is usually considered a "second-line," slow-acting, disease-modifying treatment.
We sought to test whether SCIT is as effective as antisymptomatic treatment in the control of symptoms in patients with SAR in the first year of treatment.
We reviewed meta-analyses with 5 or more randomized, double-blind, placebo-controlled trials of SCIT or antisymptomatic treatment in patients with SAR. We then selected trials measuring the total nasal symptom score (TNSS), the total symptom score (TSS), or both during the first pollen season after treatment initiation. Efficacy was determined as the percentage reduction in TSSs and TNSSs obtained with active treatment compared with placebo (relative clinical impact [RCI]) and the standardized mean difference (SMD) of treatment verses placebo (effect size [ES]).
The weighted mean RCI of SCIT on TNSSs (-34.7% ± 6.8%) was higher than those of mometasone (-31.7% ± 16.7%, P < .00001) and montelukast (-6.3% ± 3.0%, P < .00001). The weighted mean RCI of SCIT on TSSs (-32.9% ± 12.7%) was higher than that of desloratadine (-12.0% ± 5.1%, P < .00001). The overall ES of SCIT in terms of TNSSs (SMD, -0.94; 95% CI, -1.45 to -0.43) was similar to that of mometasone (SMD, -0.47; 95% CI, -0.63 to -0.32; P > .05) and higher than that of montelukast (SMD, -0.24; 95% CI, -0.33 to -0.16; P < .05). The overall ES of SCIT in terms of TSSs (SMD, -0.86; 95% CI, -1.17 to -0.55) was comparable with that of desloratadine (SMD, -1.00; 95% CI, -1.68 to -0.32; P > .05).
Our data provide indirect but consistent evidence that SCIT is at least as potent as pharmacotherapy in controlling the symptoms of SAR as early as the first season of treatment.

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    • "In an indirect comparison (as previously performed for SCIT by Matricardi et al. [23]), the administration of grass pollen SLIT tablets was associated with a greater RCI (versus placebo) on symptoms than that provided by second-generation H1-antihistamines and a leukotriene receptor antagonist - medications that clearly ‘work’ in clinical practice and whose efficacy is not called into question. These RCIs were obtained despite the presence of methodological factors that mask the efficacy of SLIT. "
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    ABSTRACT: Background The capacity of sublingual allergen immunotherapy (SLIT) to provide effective symptom relief in pollen-induced seasonal allergic rhinitis is often questioned, despite evidence of clinical efficacy from meta-analyses and well-powered, double-blind, placebo-controlled randomized clinical trials. In the absence of direct, head-to-head, comparative trials of SLIT and symptomatic medication, only indirect comparisons are possible. Methods We performed a meta-analysis of classes of products (second-generation H1-antihistamines, nasal corticosteroids and grass pollen SLIT tablet formulations) and single products (the azelastine-fluticasone combination MP29-02, and the leukotriene receptor antagonist montelukast) for the treatment of seasonal allergic rhinitis in adults, adolescents and/or children. We searched the literature for large (n >100 in the smallest treatment arm) double-blind, placebo-controlled randomized clinical trials. For each drug or drug class, we performed a meta-analysis of the effect on symptom scores. For each selected trial, we calculated the relative clinical impact (according to a previously published method) on the basis of the reported post-treatment or season-long nasal or total symptom scores: 100 × (scorePlacebo - scoreActive)/scorePlacebo. Results Twenty-eight publications on symptomatic medication trials and ten on SLIT trials met our selection criteria (total number of patients: n = 21,223). The Hedges' g values from the meta-analyses confirmed the presence of a treatment effect for all drug classes. In an indirect comparison, the weighted mean (range) relative clinical impacts were -29.6% (-23% to -37%) for five-grass pollen SLIT tablets, -19.2% (-6% to -29%) for timothy pollen SLIT tablets, -23.5% (-7% to -54%) for nasal corticosteroids, -17.1% (-15% to -20%) for MP29-02, -15.0% (-3% to -26%) for H1-antihistamines and -6.5% (-3% to -10%) for montelukast. Conclusions In an indirect comparison, grass pollen SLIT tablets had a greater mean relative clinical impact than second-generation antihistamines and montelukast and much the same mean relative clinical impact as nasal corticosteroids. This result was obtained despite the presence of methodological factors that mask the clinical efficacy of SLIT for the treatment of seasonal allergic rhinitis.
    BMC Medicine 05/2014; 12(1):71. DOI:10.1186/1741-7015-12-71 · 7.25 Impact Factor
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    • "Together with the potential range of benefits following SIT, reduction in symptoms is mandatory. Recently, an overview of how effective SIT is in reducing symptoms including a comparison to the effectiveness of symptomatic treatment options was published [50]. The data support that already during the first seasonal exposure after initiation of SCIT a reduction in symptoms at least as potent as the reduction following treatment with symptomatic drugs can be achieved. "
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    ABSTRACT: Allergen Specific Immunotherapy (SIT) for respiratory allergic diseases is able to significantly improve symptoms as well as reduce the need for symptomatic medication, but SIT also has the capacity for long-term clinical effects and plays a protective role against the development of further allergies and symptoms. The treatment acts on basic immunological mechanisms, and has the potential to change the pathological allergic immune response. In this paper we discuss some of the most important achievements in the documentation of the benefits of immunotherapy, over the last 2 decades, which have marked a period of extensive research on the clinical effects and immunological background of the mechanisms involved. The outcome of immunotherapy is described as different levels of benefit from early reduction in symptoms over progressive clinical effects during treatment to long-term effects after discontinuation of the treatment and prevention of asthma. The efficacy of SIT increases the longer it is continued and immunological changes lead to potential long-term benefits. SIT alone and not the symptomatic treatment nor other avoidance measures has so far been documented as the therapy with long-term or preventive potential. The allergic condition is driven by a subset of T-helper lymphocytes (Th2), which are characterised by the production of cytokines like IL-4, and IL-5. Immunological changes following SIT lead to potential curative effects. One mechanism whereby immunotherapy suppresses the allergic response is through increased production of IgG4 antibodies. Induction of specific IgG4 is able to influence the allergic response in different ways and is related to immunological effector mechanisms, also responsible for the reduced late phase hyperreactivity and ongoing allergic inflammation. SIT is the only treatment which interferes with the basic pathophysiological mechanisms of the allergic disease, thereby creating the potential for changes in the long-term prognosis of respiratory allergy. SIT should not only be recognised as first-line therapeutic treatment for allergic rhinoconjunctivitis but also as secondary preventive treatment for respiratory allergic diseases.
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