Sublingual allergoid immunotherapy: a new 4-day induction phase in patients allergic to house dust mites.

Sublingual immunotherapy with monomeric allergoid (allergoid SLIT), given according to the standard scheme, has proved effective and safe in many clinical trials. However, its build-up phase requires a long time ranging from 16 days to 14 weeks. This study therefore investigated whether, with a four-day up-dosing, the same benefit could be achieved in a shorter time. Thirty rhinitic and/or asthmatic patients (16 M and 14 F, mean age 36+/-8.2 years) allergic to house dust mites (HDM) with or without other sensitizations were randomized to allergoid SLIT or standard drug therapy. The build-up phase lasted four days. The first day the patients took a 300 AU tablet, the second day two 300 AU tablets, the third day three 300 AU tablets and the fourth day four 300 AU tablets. The total amount taken during the up-dosing was 3000 AU. Patients were then treated for 12 months at the dosage of 2000 AU/week (total amount of allergen: 104,000 AU/year). The symptom score and drug consumption were recorded from November to February on monthly diary cards. At baseline and after 12 months a Visual Analogue Scale (VAS) was used to rate the patients? well-being. Skin prick test reactivity was evaluated before and after the 12-month treatment in both groups using 10 mg/mL histamine as reference. VAS scores rose significantly (about 45%) in both groups in comparison to baseline (p=0.001). In addition, there was a significantly greater reduction of the global symptoms score (about 52%) - but not in drug consumption - in the SLIT group in comparison to controls (p=0.0004). The SLIT group showed a highly significant reduction (about 39%) in skin prick test reactivity (p=0.000003) while the control group remained unchanged (p=0.5226). No severe adverse events were observed. Even with this short four-day up-dosing, the allergoid SLIT proves to be safe. In addition, it is already effective in patients allergic to HDM after 12 months, and significantly reduces allergen-specific skin reactivity.

Parietaria sublingual allergoid immunotherapy with a co-seasonal treatment schedule.

BACKGROUND: Sublingual immunotherapy (SLIT) with monomeric allergoid, given according to the standard scheme, resulted effective and safe. However, the achievement of a clinical benefit requires a long time. We thus performed this study using an administration protocol starting in the co-seasonal period with a 3-day build-up phase and lasting only 6 months, in order to obtain the above benefit in a shorter time. METHODS AND RESULTS: The study, prospective, randomised and controlled versus drug therapy, was conducted on 65 rhinitic and/or asthmatic patients allergic to Parietaria with or without other sensitisations. Twenty-four were allocated to 1,000 AU/week, 21 to 3,000 AU/week and 21 to drug therapy. They were treated from April to September 2006. At baseline, 3 and 6 months a Visual Analogue Scale (VAS) was performed to assess the patients' well-being. Drug consumption was evaluated by means of monthly diary cards. Bronchial reactivity was investigated at baseline and 6 months by methacholine challenge test. There was a greater VAS improvement in both the SLIT groups than in the controls after 6 months (p<0.05). In patients taking 3,000 AU/week this was already evident after 3 months. There was a significant reduction in rescue medication consumption between 3 and 6 months (p<0.05) in all three groups. The bronchial reactivity was reduced only in the SLIT groups (p<0.001). No adverse events were observed. CONCLUSIONS: At 6 months the allergoid SLIT showed itself to be effective and safe. In addition the subjective clinical benefit was obtained in a more rapid period, i.e. 3 instead of 6 months, when a higher maintenance dose was administered.

Pharmacoeconomics of subcutaneous allergen immunotherapy.

The current burden of allergic diseases, estimated by both direct and indirect costs, is very relevant. In fact the cost estimation for rhinitis amount globally to 4-10 billion dollars/year in the U.S. and to an average annual cost of 1089 euros per child/adolescent and 1543 euros per adult in Europe. The estimated annual costs in Northern America for asthma amounted to 14 billion dollars. Consequently, preventive strategies aimed at reducing the clinical severity of allergy are potentially able to reduce its costs. Among them, specific immunotherapy (SIT) joins to the preventive capacity the carryover effect once treatment is discontinued. A number of studies, mainly conducted in the US and Germany demonstrated a favourable cost-benefit balance. In the nineties, most surveys on patients with allergic rhinitis and asthma reported significant reductions of the direct and indirect costs in subjects treated with SIT compared to those treated with symptomatic drugs. This is fully confirmed in recent studies conducted in European countries: in Denmark the direct cost per patient/year of the standard care was more than halved following SIT; in Italy a study on Parietaria allergic patients demonstrated a significant difference in favor of SIT plus drug treatment for three years versus drug treatment alone, with a cost reduction starting from the 2nd year and increasing to 48% at the 3rd year, with a highly statistical significance which was maintained up to the 6th year, i.e. 3 years after stopping immunotherapy, corresponding to a net saving for each patient at the final evaluation of 623 euros per year; in France a cost/efficacy analysis comparing SIT and current symptomatic treatment in adults and children with dust mite and pollen allergy showed remarkable savings with SIT for both allergies in adults and children.

Practice parameters for sublingual immunotherapy.

The efficacy and safety of sublingual immunotherapy (SLIT) are currently supported by clinical trials, meta-analysis and post-marketing surveys. Practice parameters for clinical use of SLIT are proposed here by a panel of Italian specialists, with reference to evidence based criteria. Indications to SLIT include allergic rhinoconjunctivitis, asthma, and isolated conjunctivitis (strength of recommendation: grade A). As to severity of the disease, SLIT is indicated in moderate/severe intermittent rhinitis, persistent rhinitis and mild to moderate asthma (grade D). SLIT may be safely prescribed also in children aged three to five years (grade B), and its use in subjects aged more than 60 years is not prevented when the indications and contraindication are ascertained (grade D). The choice of the allergen to be employed for SLIT should be made in accordance with the combination of clinical history and results of skin prick tests (grade D). Polysensitisation, i.e. the occurrence of multiple positive response does not exclude SLIT, which may be done with the clinically most important allergens (grade D). As to practical administration, co-seasonal, pre co-seasonal, and continuous schedules are available, being the latter recommended for perennial allergens or for pollens with particularly prolonged pollination, such as Parietaria (grade D). For pollens with relatively short pollination, such as grasses and trees (cypress, birch, alder, hazelnut, olive) the pre co-seasonal and perennial schedules are preferred (grade C). The build-up phases suggested by manufacturers can be safely used (grade A), but they can be modified according to the patient's tolerance (grade C). A duration of SLIT of 3-5 years is recommended to ensure a long-lasting clinical effect after the treatment has been terminated (grade C).

Safety and tolerability of ultra-rush (20 minutes) sublingual immunotherapy in patients with allergic rhinitis and/or asthma.

BACKGROUND: The safety and good tolerability of sublingual immunotherapy (SLIT) has already been proved in allergic patients, but only one study has investigated the occurrence of immediate adverse reactions in allergic patients after a 2-hour ultra-rush regimen of SLIT performed with a chemically modified extract (sublingual monomeric allergoid, Lais, Lofarma S.p.A., Milan). The objective of the present study was to evaluate the occurrence of immediate adverse reactions in allergic patients after a very fast (20 minutes) ultra-rush regimen of sublingual allergoid SLIT. METHODS AND RESULTS: We studied 105 patients: 28 children (20 male, mean age 13.3 +/- 2.1 yr) and 77 adults (29 male, mean age 34.7 +/- 9.9 years) with a history of intermittent/persistent rhinitis or intermittent/mild persistent asthma due to House Dust Mite (n = 56), Parietaria (n = 34) and Timothy-grass (n = 15) The build-up ultra-rush phase involved the administration, every five minutes, of increasing doses of the sublingual allergoid SLIT. All patients tolerated the treatment very well. Only one patient out of 105 (0.9%) had a mild local symptoms (gastric pirosis) that occurred 30 minutes after the last initial dose and spontaneously disappeared as the treatment was continued. CONCLUSIONS: These data show the excellent safety and tolerability profile of an ultra-rush SLIT regimen performed with a chemically modified extract, even when high doses were administered through an extremely short induction phase (20 minutes), thus confirming the previously reported results.

Safety and tolerability of ultra-rush (20 minutes) sublingual immunotherapy in patients with allergic rhinitis and/or asthma

Background: The safety and good tolerability of sublingual immunotherapy (SLIT) has already been proved in allergic patients, but only one study has investigated the occurrence of immediate adverse reactions in allergic patients after a 2-hour ultra-rush regimen of SLIT performed with a chemically modified extract (sublingual monomeric allergoid, Lais®, Lofarma S.p.A., Milan). The objective of the present study was to evaluate the occurrence of immediate adverse reactions in allergic patients after a very fast (20 minutes) ultra-rush regimen of sublingual allergoid SLIT. Methods and results: We studied 105 patients: 28 children (20 male, mean age 13.3 ± 2.1 yr) and 77 adults (29 male, mean age 34.7 ± 9.9 years) with a history of intermittent/persistent rhinitis or intermittent/mild persistent asthma due to House Dust Mite (n = 56), Parietaria (n = 34) and Timothy-grass (n = 15) The build-up ultra-rush phase involved the administration, every five minutes, of increasing doses of the sublingual allergoid SLIT. All patients tolerated the treatment very well. Only one patient out of 105 (0.9 %) had a mild local symptom (gastric pirosis) that occurred 30 minutes after the last initial dose and spontaneously disappeared as the treatment was continued. Conclusions: These data show the excellent safety and tolerability profile of an ultra-rush SLIT regimen performed with a chemically modified extract, even when high doses were administered through an extremely short induction phase (20 minutes), thus confirming the previously reported resultsBackground: The safety and good tolerability of sublingual immunotherapy (SLIT) has already been proved in allergic patients, but only one study has investigated the occurrence of immediate adverse reactions in allergic patients after a 2-hour ultra-rush regimen of SLIT performed with a chemically modified extract (sublingual monomeric allergoid, Lais®, Lofarma S.p.A., Milan). The objective of the present study was to evaluate the occurrence of immediate adverse reactions in allergic patients after a very fast (20 minutes) ultra-rush regimen of sublingual allergoid SLIT. Methods and results: We studied 105 patients: 28 children (20 male, mean age 13.3 ± 2.1 yr) and 77 adults (29 male, mean age 34.7 ± 9.9 years) with a history of intermittent/persistent rhinitis or intermittent/mild persistent asthma due to House Dust Mite (n = 56), Parietaria (n = 34) and Timothy-grass (n = 15) The build-up ultra-rush phase involved the administration, every five minutes, of increasing doses of the sublingual allergoid SLIT. All patients tolerated the treatment very well. Only one patient out of 105 (0.9 %) had a mild local symptoms (gastric pirosis) that occurred 30 minutes after the last initial dose and spontaneously disappeared as the treatment was continued. Conclusions: These data show the excellent safety and tolerability profile of an ultra-rush SLIT regimen performed with a chemically modified extract, even when high doses were administered through an extremely short induction phase (20 minutes), thus confirming the previously reported results

Antecedentes: La seguridad y la buena tolerancia de la inmunoterapia por via sublingual (ITSL) se ha comprobado en pacientes alérgicos, pero solamente en un estudio se ha investigado la aparición de reacciones adversas inmediatas en pacientes alérgicos que siguen una pauta de inmunoterapia sublingual ultra rápida de dos horas, administrando un extracto químicamente modificado (alergoide monomérico sublingual, Lais®, Lofarma S.p.A., Milan). El objetivo del presente estudio fue evaluar la aparición de reacciones adversas inmediatas en pacientes alérgicos con un régimen de dosificación ultra rápido (20 minutos) de un alergoide sublingual (ITSL). Métodos y resultados: Estudiamos 105 pacientes: 28 niños (20 varones, promedio de edad 13.3 ± 2.1 años) y 77 adultos (29 varones, promedio de edad 34.7 ± 9.9 años) cuyas historias clínicas registraron rinitis intermitente/leve persistente causada por ácaros del polvo (n = 56), Parietaria (n = 34) y fleo de los prados (Timothy grass) (n = 15). La fase de concentración ultra rápida consistió en la administración por via sublingual de dosis crecientes del alergoide cada cinco minutos. Todos los pacientes toleraron el tratamiento satisfactoriamente. Sólo un paciente entre los 105 (0,9 %) presentó síntomas locales level (pirosis gástrica) durante los 30 minutos posteriores a la última dosis inicial que remitieron cuando se discontinuó el tratamiento. Conclusiones: Estos datos demuestran el excelente nivel de seguridad y tolerancia de un régimen de dosificación ultra rápido de ITSL con un extracto químicamente modificado, aún con la administración de dosis elevadas durante una fase de inducción extremamente corta (20 minutos), lo cual confirma los resultados anteriormente presentados

Safety and tolerability of ultra-Rush (20 minutes) sublingual immunotherapy in patients with allergic rhinitis and/or asthma.

BACKGROUND: The safety and good tolerability of sublingual immunotherapy (SLIT) has already been proved in allergic patients, but only one study has investigated the occurrence of immediate adverse reactions in allergic patients after a 2-hour ultra-rush regimen of SLIT performed with a chemically modified extract (sublingual monomeric allergoid, Lais, Lofarma S.p.A., Milan). The objective of the present study was to evaluate the occurrence of immediate adverse reactions in allergic patients after a very fast (20 minutes) ultra-rush regimen of sublingual allergoid SLIT. METHODS AND RESULTS: We studied 105 patients: 28 children (20 male, mean age 13.3 +/- 2.1 yr) and 77 adults (29 male, mean age 34.7 +/- 9.9 years) with a history of intermittent/persistent rhinitis or intermittent/mild persistent asthma due to House Dust Mite (n = 56), Parietaria (n = 34) and Timothy-grass (n = 15) The build-up ultra-rush phase involved the administration, every five minutes, of increasing doses of the sublingual allergoid SLIT. All patients tolerated the treatment very well. Only one patient out of 105 (0.9%) had a mild local symptom (gastric pirosis) that occurred 30 minutes after the last initial dose and spontaneously disappeared as the treatment was continued. CONCLUSIONS: These data show the excellent safety and tolerability profile of an ultra-rush SLIT regimen performed with a chemically modified extract, even when high doses were administered through an extremely short induction phase (20 minutes), thus confirming the previously reported results.

Clinical experience with two twice daily slow release theophylline preparations. Relation between serum theophylline concentrations, effectiveness, tolerability and compliance in elderly patients.

The relation between serum theophylline concentrations, effectiveness, tolerability and compliance were evaluated in 14 hospitalized elderly patients with broncho-obstructive pathology, using a new twice daily sustained release theophylline suspension compared to standard twice daily slow release tablets. The results showed that the mean theophylline serum concentration remains within the therapeutic range with both preparations. No significant difference exists between the two treatments with regard to effectiveness. Tolerability and compliance of the theophylline suspension, however, were higher.