Cost-effectiveness of grass pollen subcutaneous immunotherapy (SCIT) compared to sublingual immunotherapy (SLIT) and symptomatic treatment in Austria, Spain, and Switzerland.

BACKGROUND: While specific immunotherapy (SIT) has been proven to be cost-effective for the treatment of allergic rhinitis compared to symptomatic treatment, there is a lack of European studies in which sublingual (SLIT) and subcutaneous (SCIT) immunotherapy were compared. The present analysis is focused on the cost-effectiveness of SCIT compared to SLIT and symptomatic treatment of grass pollen allergy in Austria, Spain, and Switzerland. It will address specific properties of the underlying healthcare systems. METHODS: The investigation is based on a previously published health economic model calculation. This was designed as a Markov model with pre-defined health stages and a duration of 9 years covering specific preparations for SCIT (Allergovit) and SLIT (Oralair). The effectiveness was assessed as symptom-score based quality-adjusted life years (QALYs). Additionally, total cost has been determined as well as the cost-effectiveness of SCIT. The robustness of model results was proved in further sensitivity analyses. RESULTS: With regard to the effectiveness of both SCIT and SLIT, preparations were dominant compared to pharmacological symptomatic therapy. Both strategies were associated with additional cost, but, combined with the results on effectiveness, both have to be regarded as cost-effective. A direct comparison of the SCIT (Allergovit) and SLIT (Oralair) showed lower total costs of SCIT vs SLIT for Austria, Spain, and Switzerland (€1,368 vs €2,012, €2,229 vs €2,547, and €1,901 vs €2,220) and superior effectiveness (SCIT =8.02 QALYs; SLIT =7.98 QALYs; and symptomatic therapy =7.90 QALYs). CONCLUSION: In patients with allergic rhinitis, SIT offers cost-effective treatment options compared to symptomatic treatment. When comparing SCIT (Allergovit) and SLIT (Oralair), SCIT was dominant in terms of QALYs as well as costs, in particular due to a slightly higher patient compliance and lower drug costs.

Objective eliciting doses of peanut-allergic adults and children can be combined for risk assessment purposes.

BACKGROUND: To improve food labelling strategies, information regarding eliciting doses (EDs) and the effect of patient characteristics on these EDs is necessary. OBJECTIVE: To establish EDs for objective and subjective symptoms and analyse the effect of sensitization levels and other patient characteristics on threshold distribution curves (TDCs). METHODS: Threshold data from 100 adults and 262 children with a positive food challenge were analysed with interval-censoring survival analysis (ICSA) and fitted to a TDC from which EDs could be extracted. Possible influencing factors were analysed as covariates by ICSA. A hazard ratio (HR) was calculated in case of a significant effect. RESULTS: TDCs for both objective and subjective symptoms were significantly different between adults and children (P < 0.001). Objective ED05 values, however, were comparable (2.86 mg peanut protein in adults and 6.38 mg in children). Higher levels of sIgE to Ara h 2 and peanut extract were associated with a larger proportion of patient groups reacting to a dose increase with objective symptoms (adults and children) or subjective symptoms (adults, in children a trend). Age had a similar effect in children (HR 1.05 for objective symptoms and 1.09 for subjective symptoms). Gender had no effect on TDCs. CONCLUSION AND CLINICAL RELEVANCE: Subjective and objective TDCs were different between adults and children, but objective ED05 values were comparable, meaning that threshold data from children and adults can be combined for elaboration of reference doses for risk assessment. Higher sIgE levels to Ara h 2 and peanut extract were associated with a larger proportion of both patient groups to react to a certain dose increase.

Implementation of pre-seasonal sublingual immunotherapy with a five-grass pollen tablet during optimal dosage assessment.

BACKGROUND: The optimal dose (300IR) of a five-grass pollen sublingual immunotherapy tablet in terms of efficacy was previously demonstrated from the first pollen season. OBJECTIVE: Here, we aim to confirm whether this dose remained optimal during the peak of the pollen season by assessing the efficacy and quality of life data. METHODS: A total of 628 subjects with grass pollen rhinoconjunctivitis were randomized in a double-blind, placebo-controlled, multi-centre, pan-European trial. Subjects received once-daily tablets (Stallergenes, Antony, France) of 100IR, 300IR, 500IR or placebo, starting 4 months before and throughout the 2005 grass pollen season. The pollen season was defined as the first day of 3 consecutive days with a grass pollen count above 30 grains/m(3) of air, recorded using Hirst-type volumetric pollen traps, to the last day before 3 consecutive days with a pollen count below 30 grains/m(3). RESULTS: The grass pollen season lasted an average of 30 days, with a peak of 12 days. The mean treatment duration before the grass pollen season was similar in the four treatment groups (121.4+/-31.1 to 128.6+/-15.4 days in the safety population). Both the 300IR and 500IR groups had highly significant improvements in Rhinoconjunctivitis Total Symptom Score (RTSS) vs. placebo at the peak pollen season (P=0.0005 and 0.0014, respectively), which agreed with improvements in RTSS in the primary evaluations. The average RTSS scores were slightly elevated during the peak pollen season in all treatment groups. The overall Rhinoconjunctivitis Quality of Life Questionnaire score confirmed the optimal dosage 300IR at peak (P<0.0001) and at the end (P< or =0.0031) of the pollen season. All doses were well tolerated. CONCLUSION: At the peak pollen season, the efficacy and quality of life data for both 300IR and 500IR groups was significantly improved vs. the placebo group. These results confirm the conclusions of the primary evaluations and validate the use of 300IR tablets for clinical practice.

Assessment of lupin allergenicity in the cholera toxin model: induction of IgE response depends on the intrinsic properties of the conglutins and matrix effects.

BACKGROUND: The well-established murine model of IgE-mediated food allergy, based on oral administration of antigen and cholera toxin (CT), has within the previous years been used to evaluate various food proteins. Nonetheless, little knowledge on the factors that determine the allergenicity of food proteins is available so far. The use of proteins from the legume seed Lupinus albus as food ingredients calls for an evaluation of their allergenic potential, and therefore, we applied the cited model to investigate the putative allergenicity of three lupin protein preparations representing different matrices in which the four types of conglutins are present in varying concentrations. METHODS: Weekly, BALB/c A mice were orally immunized with the three lupin protein products together with CT. Total specific antibodies and IgE were determined by ELISA and Western blotting. RESULTS: A dose-dependent Ig response against the analyzed proteins was observed for all three lupin products, while IgE responses against conglutins beta, gamma and delta, but not against conglutin alpha, were primarily detected after oral administration of lupin flakes. Whereas no differences among the samples for total specific Ig responses were seen, orally administered lupin flake extracts were much more efficient in inducing a conglutin-specific IgE response compared with fractionated lupin protein products. CONCLUSIONS: Although the lupin-specific Ig response induced by coadministration of CT and lupin proteins appears to be dose dependent, the IgE response appears to depend merely on some intrinsic properties of the proteins as well as some factors of the protein matrix.

Plant-derived vaccines: a look back at the highlights and a view to the challenges on the road ahead.

The sobering reality is that each year, 33 million children remain unvaccinated for vaccine-preventable diseases. Universal childhood vaccination would have profound effects on leveling the health inequities in many parts of the world. As an alternative to administration of vaccines by needle and syringe, oral vaccines offer significant logistical advantages, as the polio eradication campaign has demonstrated. Over the past decade, the expression of subunit vaccine antigens in plants has emerged as a convenient, safe and potentially economical platform technology, with the potential to provide a novel biotechnological solution to vaccine production and delivery. As this technology has come of age, many improvements have been made on several fronts, as a growing number of research groups worldwide have extensively investigated plants as factories for vaccine production. This review attempts to highlight some of the achievements over the past 15 years, identify some of the potential problems and discuss the promises that this technology could fulfill.