Efficacy Of Sublingual Immunotherapy Research Articles

New approaches to the design of sublingual immunotherapy clinical trials

The aim of this article is to assess and discuss the recently raised key issues concerning the new approaches in conducting clinical trials for sublingual immunotherapy (SLIT), with a special remark on the need for real-life studies exploring those factors able to affect the clinical relevance of the treatment. Although SLIT clinical efficacy in respiratory allergy has been investigated by numerous double-blind, randomized trials and meta-analyses, shortcomings in the execution and reporting of some studies may explain the difficulties in identifying a potential role of SLIT for allergic diseases therapy. This issue prompted the international scientific communities to discuss and reach a consensus on the mainstays to follow during clinical trial designing, carrying out and reporting. It was found that particular attention should be paid to the methodological aspects. Indications about patients’ selection, baseline assessment, statistical analysis, choice of primary and secondary end points and types of allergen vaccines have been suggested to ensure the robustness of findings. The Consolidated Standards of Reporting Trials checklist should be considered in the phase of reporting the studies to improve transparency, paying attention to the measures aimed at reducing the probability of selection and publication bias. Being safe is a crucial aspect, uniform classifications of adverse events are also desirable to support reliable assessments worldwide. Beyond methodological issues, SLIT should be explored in the context of real-life studies. Clinical trials, rigorous in their methodology and characteristics, extended to all the most relevant allergens, are needed to provide clear evidence of short-term and disease-modifying effects of SLIT in respiratory allergy.

One Century of Allergen-Specific Immunotherapy for Respiratory Allergy

Among the treatments available for respiratory allergy, which include allergen avoidance and pharmacotherapy, specific immunotherapy (SIT) is the only treatment able to not only act on the symptoms of allergy but also act on the causes. SIT is the practice of administering gradually increasing doses of the specific causative allergen to reduce the clinical reactivity of allergic subjects and was introduced one century ago. SIT remained an empirical treatment for more than 40 years, but the first controlled trial in 1954 paved the way for the scientific era. At present, SIT may be administered in two forms: subcutaneous (SCIT) and sublingual immunotherapy (SLIT). A large number of trials, globally analyzed in several meta-analyses, evaluated the efficacy and safety of SCIT and SLIT in allergic rhinitis and asthma. Current available data give solid evidence to the clinical efficacy of both SCIT and SLIT in allergic rhinitis and asthma. Providing the recommended doses and administration schedules are adhered to, the safety and tolerability are very good; however, adverse systemic reactions remain a drawback for SCIT. After one century of use, accumulating evidence surrounds SIT and the central role in the management of respiratory allergy.

Clinical efficacy and safety of sublingual immunotherapy using standardized Dermatophagoides farinae extract for children with combined allergic rhinitis and asthma syndrome

To study the clinical efficacy of sublingual immunotherapy using standardized Dermatophagoides farinae extract for children with combined allergic rhinitis and asthma syndrome. Fifty-two children, from 4 to 14 years of age, with mite-sensitive combined allergic rhinitis and asthma syndrome were treated sublingually with standardized Dermatophagoides farinae extract. The clinical efficacy was evaluated by monthly follow-up visits. After treatment for 1 or 2 years using the standardized Dermatophagoides farinae extract, the asthma and rhinitis symptom scores, medication scores and adverse reactions before and after treatment were evaluated. SPSS 17.0 software was used to analyze the data. The allergic asthma symptom scores before treatment during the day were 3.22 ± 0.66 and at night 2.05 ± 0.57. After 1 year of treatment, the day and night scores (1.68 ± 0.61, 0.94 ± 0.32) respectively, were decreased significantly (q values were 15.25 and 13.78 respectively, all P < 0.01). After 2 years of treatment, the scores (0.61 ± 0.28, 0.43 ± 0.13) were also decreased significantly (q values were 10.29 and 6.07 respectively, all P < 0.01). The allergic rhinitis symptom scores and medication scores were 2.34 ± 0.59 and 3.09 ± 1.01 respectively before treatment and 1.21 ± 0.46 and 1.89 ± 0.64 after 1 year of treatment. The differences were significant (q values were 15.48 and 18.61 respectively, all P < 0.01). The allergic rhinitis symptom scores and medication scores were 1.02 ± 0.37 and 1.49 ± 0.38 after 2 years of treatment. There was no significant difference between 2 years of treatment and 1 year of treatment (q values were 2.53 and 2.78 respectively, all P > 0.05). There were no severe adverse events during the treatment, except for mild mouth cavity discomfort. Sublingual immunotherapy using standardized Dermatophagoides farinae extract is safe and effective in the treatment of children with combined allergic rhinitis and asthma syndrome.

Specific immunotherapy in children

Subcutaneous immunotherapy (SCIT) with allergen extracts in children with allergic rhinitis, with or without co-seasonal asthma, has developed into a routine treatment although the scientific evidence for its efficacy is not as strong as for adults. In the hands of experienced allergists, this treatment has been proven to be safe. The development of allergen tablets for sublingual immunotherapy (SLIT) may open a new age of more convenient, safer SIT. In children, in particular, the evidence for the long-term efficacy of SLIT, its ability to prevent the development of asthma and polysensitization and its comparability to SCIT will be required before it will replace the traditional subcutaneous route. Issues of compliance represent an important drawback of SLIT. We need ways of improving this. Treatment of asthma by immunotherapy is still restricted to clearly defined patients with mild to moderate asthma with symptoms that are related to the specific allergen sensitization. In these patients, symptoms and use of anti-inflammatory therapy can be reduced by SIT.

Efficacy of sublingual immunotherapy with house dust mite extract in polyallergen sensitized patients with allergic rhinitis

It is suggested that polysensitized patients might not benefit from specific allergic rhinitis immunotherapy as much as monosensitized patients, although further research on this subject is needed. To compare the efficacy of sublingual immunotherapy (SLIT) with standardized house dust mite extract in monosensitized and polysensitized patients with allergic rhinitis. Patients who were sensitized to house dust mites and treated with SLIT for house dust mites for at least 1 year between November 2007 and March 2010 were studied. The monoallergen sensitized group was defined as patients who were sensitized to Dermatophagoides pteronyssinus and/or Dermatophagoides farinae (n = 70). The polyallergen sensitized group was defined as patients who were simultaneously sensitized to house dust mites and other allergens (n = 64). A standardized extract of house dust mites was used for immunotherapy. Antiallergic medication and the total nasal symptom score (TNSS), including rhinorrhea, sneezing, nasal obstruction, and itchy nose, were evaluated before and 1 year after SLIT. This study enrolled 134 patients. The TNSS improved significantly after SLIT in both groups, whereas the change in the TNSS did not differ significantly between the groups. The antiallergic medication scores also decreased significantly in both groups, but there was no significant difference between the groups. In polysensitized allergic rhinitis patients, SLIT for D pteronyssinus and/or D farinae produced improvements in both nasal symptoms and rescue medication scores comparable to those in monosensitized patients, regardless of other positive allergens. SLIT for D pteronyssinus and/or D farinae should be considered in polysensitized allergic rhinitis patients.

Sublingual immunotherapy for allergic rhinitis: an update

Sublingual immunotherapy (SLIT) has progressively gained credibility. Randomized double-blind placebo-controlled trials, meta-analyses and mechanistic studies have accumulated rapidly in the last years. We will review herein a brief history of SLIT, its indications and the safety aspects and will discuss the main unmet needs and the points to be developed in the field. During the last year, new information on SLIT has become available, mainly from the so-called big trials, and some important aspects have been partially clarified. In addition, the possible indications to SLIT began to be expanded. The dose dependency of the efficacy of SLIT and the optimal maintenance dose have been identified at least for grass allergens. The safety is well demonstrated in both adults and children.

Sublingual Immunotherapy in Patients with Allergic Rhinoconjunctivitis

Sublingual immunotherapy (SLIT) is a well-established treatment option for allergic rhinitis in several European countries, but it is considered investigational in the United States. Studies conducted in Europe provided a large body of evidence supporting the safety and efficacy of SLIT, but those studies used allergen products that are different from those that are likely to be approved in the United States, and many of them were not controlled, randomized, double-blinded trials. This review summarize research conducted on the efficacy, safety, and mechanisms of SLIT published during the past year, with a focus on ragweed and grass antigens. Results of recent US studies document the safety and efficacy of SLIT and have started to yield insight into the mechanisms of SLIT.

Sublingual immunotherapy in asthma does not influence lymphocyte sensitivity to fas stimulation

BackgroundThe resistance of T lymphocytes to Fas-mediated apoptosis is an important feature of atopic asthma. The only effective causative treatment of atopic diseases is immunotherapy. Clinical efficacy of sublingual immunotherapy (SLIT) has been already proven, but there is still limited number of studies on its influence on lymphocytes function.ObjectivesThe aim of the study was to evaluate whether SLIT could restore the sensitivity of asthmatic T cells to undergo Fas-mediated apoptosis.Materials and methodsPeripheral blood was collected from 12 patients aged 8 ± 2 years suffering from atopic asthma and undergoing sublingual specific immunotherapy. To evaluate sensitivity to Fas-mediated apoptosis, the blood was transmitted to sterile tubes and mixed with purified monoclonal antibody anti-CD95. After incubation, leukocytes were stained with Annexin V, propidium iodide, and monoclonal antibody against CD2 conjugated with phycoerythrincyanin 5.1, and then analyzed with flow cytometry. The procedure was repeated for each patient after 12 months of SLIT.ResultsStimulation with anti-CD95 of T lymphocytes from patients with atopic asthma before treatment increased the number of early apoptotic cells (from 19.5 ± 16.7% before stimulation to 26.6 ± 16.7% Annexin V positive cells after stimulation). After one year of SLIT anti-CD95 still caused an increase of the early apoptotic cells ratio in the lymphocyte population (from 12.4 ± 7.4% before stimulation to 24.7 ± 15.4% Annexin V positive T cells after CD95 stimulation). Although an increasing trend could be observed, differences between the analyzed groups were not statistically significant.ConclusionsA year of SLIT does not change the sensitivity of T lymphocytes from peripheral blood of children suffering from atopic asthma to Fas-mediated apoptosis.

Quoi de neuf en allergologie pédiatrique en 2009 ? Partie 2: allergie oculaire et respiratoire (une revue de la littérature internationale de fin 2008 à fin 2009)

As during previous years, numerous studies have been published aiming to increase knowledge of pathophysiology, epidemiology, (early) diagnosis, prevention and treatment of respiratory allergy and asthma in children. Most important findings concern the role of new viruses (type C rhinoviruses especially) as a cause of infant bronchiolitis, and the long-lasting bronchial inflammation induced by respiratory virus infections, which may promote subsequent asthma development. Interactions between genetic and environmental (allergenic and non allergenic) factors are highlighted in several important studies, as well as statistically significant relationships between asthma and overweight/obesity. Inhaled corticosteroids associated with long-acting bronchodilators are more efficient than inhaled corticosteroids alone. Finally, several studies including numerous children show that sublingual immunotherapy is efficient in pollen and/or mite-allergic rhinitis and/or asthma in children. However, the length of efficacy of sublingual immunotherapy may be shorter than reported for subcutaneous immunotherapy.

Monomeric Allergoid Intragastric Administration Induces Local and Systemic Tolerogenic Response Involving IL-10-Producing CD4+CD25+T Regulatory Cells in Mice

The efficacy of sublingual immunotherapy, at present one of the treatments of choice for respiratory allergy, relies on the tolerance induced by oral mucosa-associated immune system; however, the gut-associated lymphoid tissue (GALT: Peyers patches and isolated lymphoid follicles) and mesenteric lymph nodes could also be involved, being stimulated by the ingested part of the allergen extract. The aim of the present study is to assess whether the exposure of the allergen exclusively to the GALT induces a tolerogenic response. For this purpose, mice were sensitized with ovalbumin or Par j 1 allergens. The corresponding gastric-resistant monomeric allergoids were then administered via orogastric gavage. After treatment, all mice were tested for: serum IgE, in vitro Th1 and Th2 cytokine release by allergen-stimulated peripheral blood lymphocytes, CD4(+)CD25(+) and CD4(+)CD25(+)IL-10(+) T cells in Peyers patches, mesenteric lymph nodes and spleen. Compared to the control, sensitized groups showed higher levels of serum IgE, lower frequency of CD4+CD25+IL-10+ T cells, at all sites, and higher amounts of in vitroreleased IL-4, IL-6 and TNF-alpha. Compared to the sensitized groups, higher frequency of CD4(+)CD25(+)IL-10(+) T cells was observed in the spleen of both Par-j 1 and OVA sensitized/treated groups and, only for ovalbumin-treated mice, in the Peyers patches and mesenteric lymph nodes, IgE and in vitro cytokines were significantly lower and equivalent to the control group. The results give the first evidence that the intragastric-restricted administration of gastric-resistant allergens restores local and peripheral tolerance in allergen-sensitized mice.

Sublingual immunotherapy for Alternaria-induced allergic rhinitis: a randomized placebo-controlled trial

Respiratory allergy due to Alternaria is a relevant clinical problem, and specific immunotherapy may represent a viable treatment option. Sublingual immunotherapy (SLIT) is safe and effective, but data for Alternaria are lacking. To assess the efficacy of standardized SLIT in patients sensitized to Alternaria in a randomized, prospective, double-blind, placebo-controlled trial. Patients with rhinitis with or without intermittent asthma and ascertained allergy to Alternaria were enrolled. After a baseline season, SLIT or matched placebo was given for 10 months. Symptoms and rescue medication intake were recorded on diary cards between June and October. Skin prick testing was performed and specific IgE, IgG4, and precipitin levels were measured at baseline and at the end of the study. Twenty-seven patients (age range, 14-42 years) were randomized, and 26 completed the study. The baseline characteristics were homogeneous in the 2 groups. After treatment, patients receiving SLIT had a significant improvement in symptoms and a reduction in medication intake vs placebo and vs the run-in season, whereas no change was seen in the placebo group. Skin prick test reactivity significantly decreased only in the SLIT group. No change was seen in specific IgG4 levels in the 2 groups, whereas Alt a 1 specific IgE levels significantly increased in the active group. One patient in the active group reported oral itching and conjunctivitis at the beginning of treatment. SLIT seems effective and safe and may represent a valuable therapeutic option in respiratory allergy due to Alternaria.

Efficacy of sublingual immunotherapy with grass allergens for seasonal allergic rhinitis: A systematic review and meta-analysis

The benefit of sublingual immunotherapy (SLIT) with grass allergens for seasonal allergic rhinitis has been extensively studied, but data on efficacy are still equivocal. To assess the effectiveness of SLIT with grass allergens in the reduction of symptoms and medication in patients with seasonal allergic rhinitis to grass pollen. Computerized bibliographic searches of MEDLINE (1995-2010) were supplemented by hand searches of reference lists. Studies were included if they were double-blind randomized controlled trials (RCTs) comparing SLIT to placebo and if they included patients with history of allergy to grass pollen treated with natural grass pollen extracts. Nineteen RCTs with 2971 patients were analyzed. The outcomes assessed were symptom and medication scores. Using a random-effects model, SLIT with grass allergens significantly reduces both symptoms (standardized mean difference, -0.32; 95% CI, -0.44 to -0.21) and medication use (standardized mean difference, -0.33; 95% CI, -0.50 to -0.16) compared with placebo. The treatment is more efficacious in adults than in children. Prolonging duration of preseasonal treatment for more than 12 weeks improves the treatment efficacy. This meta-analysis found that SLIT with grass allergens is effective in patients with seasonal allergic rhinitis compared with placebo. The benefit is clinically modest, and criteria are needed to identify patients most likely to benefit from SLIT.

Effect of Sublingual Immunotherapy on Antigen-Induced Bronchial and Nasal Inflammation in Mice

Background: Sublingual immunotherapy (SLIT) is effective in the treatment of a variety of allergic diseases, including bronchial asthma and rhinitis. However, how this local therapy exerts such wide effects is unclear. In this study, we comparatively examined the effect of SLIT on antigen-induced airway inflammation in bronchoalveolar and nasal cavities in mice. Methods: Mice were treated sublingually with ovalbumin (OVA) once a day for 2 weeks. Subsequently, they were immunized with the corresponding antigen. Following intratracheal and nasal challenge with OVA, infiltration of inflammatory cells into the bronchoalveolar and nasal cavities was investigated in these mice. Results: Massive infiltration of eosinophils as well as neutrophils into the bronchoalveolar cavity was induced by intratracheal OVA challenge. Eosinophils accumulated in the nasal cavity, but the number of neutrophils did not significantly change in response to nasal antigen challenge. These antigen-induced airway inflammatory responses, including the increases in the numbers of eosinophils and/or neutrophils in the bronchoalveolar and nasal cavities, were clearly suppressed by SLIT. Conclusions: This animal model displaying differential inflammatory responses in the bronchoalveolar and nasal cavities may be useful to elucidate the efficacy and mechanisms of SLIT against various allergic diseases.

Adherence issues related to sublingual immunotherapy as perceived by allergists

Sublingual immunotherapy (SLIT) is a viable alternative to subcutaneous immunotherapy to treat allergic rhinitis and asthma, and is widely used in clinical practice in many European countries. The clinical efficacy of SLIT has been established in a number of clinical trials and meta-analyses. However, because SLIT is self-administered by patients without medical supervision, the degree of patient adherence with treatment is still a concern. The objective of this study was to evaluate the perception by allergists of issues related to SLIT adherence. We performed a questionnaire-based survey of 296 Italian allergists, based on the adherence issues known from previous studies. The perception of importance of each item was assessed by a VAS scale ranging from 0 to 10. Patient perception of clinical efficacy was considered the most important factor (ranked 1 by 54% of allergists), followed by the possibility of reimbursement (ranked 1 by 34%), and by the absence of side effects (ranked 1 by 21%). Patient education, regular follow-up, and ease of use of SLIT were ranked first by less than 20% of allergists. These findings indicate that clinical efficacy, cost, and side effects are perceived as the major issues influencing patient adherence to SLIT, and that further improvement of adherence is likely to be achieved by improving the patient information provided by prescribers.

Efficacy of high-dose sublingual immunotherapy in children allergic to house dust mites in real-life clinical practice

Background The aim of the study was to evaluate the efficacy and safety of high-dose mite sublingual immunotherapy (SLIT) administered in children with allergic rhinitis in real-life clinical practice. Moreover, we analysed the clinical course of asthma severity. Methods Retrospective, observational, monocentre study. Medical records of patients treated between 2001 and 2008 were reviewed. Patients received a standardised Dermatophagoides pteronyssinus+ Dermatophagoides farinae extract (300 IR/ml) manufactured by Stallergenes (Staloral ® 300). Patients were evaluated before SLIT initiation and at 6, 12, 24, 36 and 48 months. Global assessment of SLIT efficacy was measured using a visual analogue scale (VAS) and a rhinitis medication consumption score (RMCS). A global asthma score was used to estimate the clinical course of asthma severity. Results We obtained data from 78 patients, 43.6% male. The mean (±SD) age was 11.0±3.0 years. Most patients (69.2%) suffered from allergic rhinitis plus asthma. Patient evaluation of allergy severity (VAS) revealed a highly significant improvement between baseline and six months (p<0.001, Wilcoxon test): 4.0±1.7 cm vs. 7.3±4.6 cm. This improvement was maintained throughout the four-year follow-up period. The use of medications (RMCS) was significantly reduced in the first six months (4.6±2.5 points at baseline vs. 0.8±1.6 points at six months visit, p<0.001, Wilcoxon test) and remained very low until the end of follow-up. We did not find a temporal improvement in asthma severity. Conclusions This retrospective study indicates that high-dose SLIT in children with rhinitis caused by house dust mites is well-tolerated and could be an effective treatment.

Sublingual immunotherapy in children with allergic polysensitization

Polysensitization is quite frequent in allergic children and may cause difficulties for the allergist in prescribing allergen-specific immunotherapy. This study aimed at evaluating the clinical effectiveness of 1 year of sublingual immunotherapy (SLIT) in a cohort of Italian allergic children with polysensitization. This open study was performed on 51 polysensitized children (34 boys; mean age, 11.8 years; range, 5.2-17.7 years) with allergic rhinitis and/or mild to moderate asthma. All of them were treated with SLIT for 1 year. The kind and the number of prescribed allergen extracts, the type of diagnosis, the severity of symptoms, and the use of drugs were evaluated at baseline and after 1 year. The adverse events to SLIT were also evaluated. Forty-two children were treated with a single extract, four with two different extracts and three with a mix of allergens. SLIT treatment induced a significant reduction in the number of sensitizations (p = 0.018); significant improvement of allergic rhinitis classification and severity; significant reduction of ocular, nasal, and bronchial symptoms (p < 0.01 for all); and drugs use (p < 0.01 for all drugs). No systemic reactions to SLIT were observed. This open study provides evidence that polysensitization is not an obstacle for prescribing SLIT in polysensitized children. Indeed, SLIT efficacy on clinical parameters is significant after 1 year and the therapy is safe.

Lactic acid bacteria as adjuvants for sublingual allergy vaccines

We compared immunomodulatory properties of 11 strains of lactic acid bacteria as well as their capacity to enhance sublingual immunotherapy efficacy in a murine asthma model. Two types of bacterial strains were identified, including: (i) potent inducers of IL-12p70 and IL-10 in dendritic cells, supporting IFN-γ and IL-10 production in CD4+ T cells such as Lactobacillus helveticus; (ii) pure Th1 inducers such as L. casei. Sublingual administration in ovalbumin-sensitized mice of L. helveticus, but not L. casei, reduced airways hyperresponsiveness, bronchial inflammation and proliferation of specific T cells in cervical lymph nodes. Thus, probiotics acting as a Th1/possibly Treg, but not Th1 adjuvant, potentiate tolerance induction via the sublingual route.

The efficacy of sublingual immunotherapy for house dust mites respiratory allergy: results of a GA²LEN meta‐analysis

Recent meta-analyses documented the efficacy and safety of sublingual immunotherapy (SLIT) in patients with allergic rhinitis (AR) and asthma (AA). Although SLIT appeared globally effective, the sub-analyses for single allergens provided uncertain results. This study is aimed to investigate the efficacy of SLIT with house dust mite (HDM) extracts in AR and AA through an updated reassessment of randomized controlled trials. Electronic databases were searched up to March 31, 2008, for randomized DBPC trials, assessing the efficacy of SLIT in AR and AA due to HDM sensitization. Outcomes were symptom scores and rescue medications use. For AR, eight studies fulfilled the selection criteria. A significant reduction in symptoms of AR (SMD -0.95; CI 95%-1.77 to -0.14 P = 0.02) was found in 194 patients (adults and children) receiving SLIT compared to 188 receiving placebo. For AA, with nine studies, similar results were found for symptoms (SMD -0.95; CI 95%-1.74 to -0.15 P = 0.02) in 243 patients (adults and children) receiving SLIT compared to 209 receiving placebo. A reduction in rescue medication use was found for AR (SMD -1.88; CI 95%-3.65 to -0.12 P = 0.04) in 89 patients, and AA (SMD -1.48; CI 95%-2.70 to -0.26 P = 0.02) in 202 patients. A relevant inter-study heterogeneity was detected. Promising evidence of efficacy for SLIT, using mite extract in allergic patients suffering from AR and AA, are herein shown. These findings suggest that more data are needed, derived from large-population-based high quality studies, and corroborated by objective outcomes, mainly for AA.

Response to sublingual immunotherapy with grass pollen extract: Monotherapy versus combination in a multiallergen extract

To date, there have been no randomized, double-blind studies showing the effectiveness of sublingual immunotherapy with multiple allergens. The purpose of this study was to examine whether the efficacy of sublingual immunotherapy (SLIT) with standardized timothy extract was reduced by combination with other allergen extracts. A single-center, randomized, double-blind, placebo-controlled trial with SLIT was conducted. After an observational grass season, SLIT was administered for 10 months to 54 patients randomized to 1 of 3 treatment arms: placebo, timothy extract (19 microg Phl p 5 daily) as monotherapy, or the same dose of timothy extract plus 9 additional pollen extracts. Symptom and medication scores were collected and titrated nasal challenges, titrated skin prick tests, specific IgE, IgG4 and cytokines release by timothy-stimulated lymphocyte proliferation were performed. Perhaps because of a very low grass pollen season in 2008, there were no significant differences in medication or symptom scores in either treatment group compared with placebo. Compared with placebo, in the timothy monotherapy group, thresholds for titrated nasal challenge and skin prick tests (P = .03 and P = .001, respectively), and serum-specific IgG4 levels (P = .005) significantly increased, and IFN- gamma levels decreased (P = .02), whereas in the multiallergen group, there was significant improvement only in the titrated skin prick tests (P = .04) which was less than in the monotherapy group. There were no significant differences between the 2 active groups in any outcome measure, and both active groups experienced more adverse events than placebo. There were no systemic reactions. Improvement in multiple relevant outcomes strongly suggests that SLIT with timothy extract alone was effective; however, the results for symptom and medication scores were not significant. The differences between multiple allergen SLIT and placebo only in skin sensitivity to timothy suggest a reduction in SLIT efficacy in this group. However, further studies are required to confirm these observations.

Sublingual immunotherapy for allergic respiratory diseases: An evaluation of meta-analyses

Five published meta-analyses (MAs) seem to prove the efficacy of sublingual immunotherapy in allergic asthma and rhinoconjunctivitis. We aimed to assess the consistency, magnitude, and robustness of the results of these MAs. The data reported in the MAs were checked with the data reported in the original studies. Funnel plots were performed to test for potential publication bias, and the trim-and-fill method was used to assess and correct the estimate of the effects if asymmetry was present. The 5 MAs included 43 studies; 17 were used in more than one MA. There were discrepancies among the MAs in the data reported from the same original studies: the MAs reported different estimates for the same outcome or the same estimates for different outcomes in 16 of those 17 studies. The MAs evaluated 15 main outcomes, 10 of which showed benefits that reached statistical significance. Funnel plots showed asymmetry in 7 outcomes, and correction by using the trim-and-fill method led to a decrease in their effect estimates and even to a loss of statistical significance in 4 of the previously significant outcomes. There was inconsistency among the MAs in the benefits when considering age, disease, allergen, or symptoms and medication use. Because of discrepancies, inconsistencies, and lack of robustness, the MAs on sublingual immunotherapy do not provide enough evidence to support its current routine management in patients with allergic asthma or rhinoconjunctivitis. Sensitivity to potential publication bias should be tested and reported in all MAs.