Simona La Piana

Efficacy of subcutaneous and sublingual immunotherapy with grass allergens for seasonal allergic rhinitis: A meta-analysis–based comparison

BACKGROUND Subcutaneous (SCIT) and sublingual (SLIT) immunotherapy are the 2 most prescribed routes for administering allergen-specific immunotherapy. They were shown to be effective in control of symptoms and in reducing rescue medication use in patients with allergic diseases, but their effectiveness has to be balanced against side effects. In recent years, SLIT has been increasingly prescribed, instead of SCIT, because of improved safety and easy administration. OBJECTIVE We assessed which route is the most effective in the treatment of patients with seasonal allergic rhinitis to grass pollen. METHODS An indirect meta-analysis-based comparison between SCIT and SLIT was performed. Treatment efficacy was determined as the standardized mean difference (SMD) in symptom and medication scores obtained with active treatment, SCIT or SLIT, compared with placebo. Studies were included if they were double-blind randomized controlled trials comparing SCIT or SLIT with placebo. Thirty-six randomized controlled trials (3014 patients; 2768 controls) were analyzed. RESULTS The overall effect size of SCIT for symptom score (SMD, -0.92; 95%CI, -1.26 to -0.58) was significantly higher than SLIT, both administered via drops (SMD, -0.25; 95% CI, -0.45 to -0.05) and tablets (SMD, -0.40; 95%CI, -0.54 to -0.27). Similar results were reported for medication score (SCIT: SMD, -0.58; 95% CI, -0.86 to -0.30. SLIT drops: SMD, -0.37; 95% CI, -0.74 to -0.00. SLIT tablets SMD, -0.30; 95% CI, -0.44 to -0.16). CONCLUSIONS Our results provide indirect but solid evidence that SCIT is more effective than SLIT in controlling symptoms and in reducing the use of antiallergic medications in seasonal allergic rhinoconjuntivitis to grass pollen.

Efficacy of Grass Pollen Allergen Sublingual Immunotherapy Tablets for Seasonal Allergic Rhinoconjunctivitis: A Systematic Review and Meta-analysis

IMPORTANCE Randomized clinical trials (RCTs) and meta-analyses of sublingual immunotherapy (SLIT) for the treatment of seasonal allergic rhinoconjunctivitis (SARC) have shown a modest clinical benefit compared with placebo. Furthermore, indirect comparison by meta-analyses showed that subcutaneous immunotherapy is more effective than SLIT. Despite these data, SLIT has become the most prescribed treatment of SARC in Europe in recent years, and it was approved by the US Food and Drug Administration for the treatment of SARC to grass pollen in the United States on April 1, 2014. OBJECTIVE To assess the efficacy and safety of the grass pollen sublingual tablets licensed as drugs in the treatment of patients with SARC to grass pollen. DATA SOURCES Computerized bibliographic searches of MEDLINE, EMBASE, the Cochrane Library, and ClinicalTrials.gov (from inception to April 30, 2014) were supplemented with a manual search of reference lists. STUDY SELECTION Randomized clinical trials were included if they compared the grass pollen SLIT tablets approved by regulatory authorities in the European Union and the United States for SARC with placebo. DATA EXTRACTION AND SYNTHESIS Data on populations, interventions, and outcomes were extracted from each RCT according to the intent-to-treat method by 2 independent observers and were combined using the method by DerSimonian and Laird. MAIN OUTCOMES AND MEASURES The primary end point was the difference in the symptom score and medication score between SLIT and placebo. We pooled data using random-effects meta-analysis, with standardized mean differences (SMDs) and 95% CIs reported. RESULTS Data were available in 13 RCTs for the symptom score (4659 patients) and in 12 RCTs for the medication score (4558 patients). We found a small treatment benefit in the symptom score (SMD, -0.28; 95% CI, -0.37 to -0.19; P < .001) and in the medication score (SMD, -0.24; 95% CI, -0.31 to -0.17; P < .001). Adverse events were reported in 1384 of 2259 patients (61.3%) receiving SLIT and in 477 of 2279 patients (20.9%) receiving placebo. Seven patients in the SLIT group reported treatment-related adverse events requiring epinephrine. CONCLUSIONS AND RELEVANCE Findings show a small benefit of the grass pollen sublingual tablets in reducing symptoms and in decreasing the use of symptomatic medication (antihistamines and corticosteroids) in patients with SARC. Considering the low magnitude of the benefit, the convenience and easy administration do not seem to be sufficient reasons for the choice of SLIT.

Differences and Similarities between Allergic and Nonallergic Rhinitis in a Large Sample of Adult Patients with Rhinitis Symptoms

Background: Allergic rhinitis (AR) and nonallergic rhinitis (NAR) may present with different clinical and laboratory characteristics. Methods: A total of 1,511 consecutive patients, aged 18–81 years, diagnosed with rhinitis, 56% females and 44% males, underwent complete allergic evaluation including skin prick test, blood eosinophil counts, nasal eosinophil counts, peak nasal inspiratory flow (PNIF) measurement and evaluation of nasal symptoms using a visual analog scale (VAS). Results: A total of 1,107 patients (73%)had AR, whereas 404 (27%) had NAR. Patients with NAR were older and predominantly female. A higher nasal eosinophils count was associated with AR and a lack of clinical response to antihistamines. AR patients had more sneezing and nasal pruritus, whereas NAR was characterized mainly by nasal obstruction and rhinorrhea. AR patients had more severe symptoms and recurrent conjunctivitis, whereas NAR patients had slightly more frequent episodes of recurring headaches as well as olfactory dysfunction. PNIF, blood eosinophil counts and VAS of nasal symptoms were higher in patients with AR. In a final logistic regression model, 10 variables were statistically different between AR and NAR: age [OR 0.97 (95% CI 0.96–0.98)], sneezing [OR 4.09 (95% CI 2.78–6.00)], nasal pruritus [OR 3.84 (95% CI 2.60–5.67)], mild symptoms [OR 0.21 (95% CI 0.09–0.49)], intermittent/severe nasal symptoms [OR 3.66 (95% CI 2.06–6.50)], VAS [OR 1.06 (95% CI 1.04–1.08)], clinical response to antihistamines [OR 22.59 (95% CI 13.79–37.00)], conjunctivitis [OR 4.49 (95% CI 2.86–7.05)], PNIF [OR 1.01 (95% CI 1.00–1.01)] and nasal eosinophil counts [OR 1.14 (95% CI 1.10–1.18)]. Receiver operating characteristic analysis showed high predictive accuracy for a model including these variables independently of the diagnosis of AR/NAR (cutoff <0.74). Conclusions: We showed that the several clinical and laboratory parameters reported above may help to reinforce or exclude the diagnosis of AR obtained with skin prick test.

Efficacy of allergen immunotherapy in reducing the likelihood of developing new allergen sensitizations: a systematic review

Guidelines and position papers indicate that allergen immunotherapy (AIT) is the only disease‐modifying treatment, including prevention of the onset of new allergen sensitizations. However, this preventive effect was shown by only a few observational studies. Our aim was to systematically review the efficacy of AIT in preventing the onset of new allergen sensitizations.

Chronic spontaneous urticaria: an autoimmune disease? A revision of the literature

The cause of chronic spontaneous urticaria has been an enigma for decades, but the recognition of functional autoantibodies in some patients with the spontaneous chronic urticaria has opened up a new concept of autoimmune urticaria. Clinical and laboratory features are in keeping with an autoimmune aetiology for many patients with otherwise inexplicable disease, but there is still debate about the importance of functional autoantibodies in the disease pathogenesis, how to test them and the clinical implications for treatment and prognosis. This review will look at the evidence for there being an autoimmune subset of urticaria, the strengths and weaknesses of the available tests in current use.

The effect of allergen immunotherapy in the onset of new sensitizations: a meta-analysis

Although the preventive efficacy of allergen immunotherapy (AIT) in the onset of new allergen sensitizations has been asserted by many reviews, position papers, and consensus conferences, the evidence available is from only 3 studies. The objective of this work was a systematic review to evaluate the preventive efficacy of AIT in the onset of new allergen sensitizations. The end‐point was the risk difference (RD) in the onset of new allergen sensitizations between patients treated with AIT and pharmacotherapy.

Comparison between statistical and fuzzy approaches for improving diagnostic decision making in patients with chronic nasal symptoms

This paper compares a fuzzy model, expressed in rule-form, with a well known statistical approach (i.e. logistic regression model) for diagnostic decision making in patients with chronic nasal symptoms. The analyses were carried out using a database obtained from a questionnaire administered to 1359 patients with nasal symptoms containing personal data, clinical data and skin prick test (SPT) results. Both the fuzzy model and the logistic regression model developed were validated using a data set obtained from another medical institution. The accuracy of the two models in identifying patients with positive or negative SPT was similar. This study is a preliminary step to the creation of a software that primary care doctors can use to make a diagnostic decision, when deciding whether patients with nasal symptoms need allergy testing or not.

Unmet Needs in Understanding Sublingual Immunotherapy to Grass Pollen

The lack of medication for allergy symptoms at the end of the last millennium has been the promoter of the idea of treating allergies as if you were treating an infectious disease, by vaccination prophylaxis. Two forms of AIT 1) subcutaneous immunotherapy (SCIT) and 2) sublingual immunotherapy (SLIT) are used in the world. Considerable interest has emerged in SLIT both scientifically and especially financially. SLIT is not a new treatment modality. First description dates back to 1900 when H. Curtis. It was relatively widely used until the late 1970’s mainly in US by homeopathic therapists. A number of case series describing experience with the oral route were published during the 1920s and 1930s, but it seems to have been perceived not as efficacious nor as well tolerated as subcutaneous immunotherapy. The companies producing allergen immunotherapy have an alliance with important opinion leaders on both shores of the Atlantic. If SLIT did not work for 40 years, why should it work for respiratory allergic diseases today? This question is the mother of all questions in the field of respiratory allergic diseases. The purpose of this chapter is to provide past and current information about immunotherapy, and discuss controversies over efficacy and safety, and dosing considerations for SLIT to grass.

Allergic Asthma and Aging

Gabriele Di Lorenzo1, Danilo Di Bona2,3, Simona La Piana2, Vito Ditta4 and Maria Stefania Leto-Barone1 1Dipartimento di Medicina Interna e Specialistica (DIMIS), Universita degli Studi di Palermo 2Dipartimento di Dipartimento di Biopatologia e Biotecnologie Mediche e Forensi, Universita degli Studi di Palermo 3Unita Operativa di Immunoematologia e Medicina Trasfusionale, Azienda Ospedaliera, Universitaria Policlinico di Palermo 4Centro Trasfusionale ASPPalermo. P.O. San Raffaele G. Giglio Cefalu, Palermo Italia