House dust mite subcutaneous immunotherapy has sustained long-term effectiveness on allergic rhinitis and asthma: A 10-year follow-up.

BACKGROUND: Maintenance doses for allergen immunotherapy (AIT) have been recommended for at least 3 years but little data on long-term efficacy is available depending on AIT duration. To show sustained efficacy 10 years after completion of treatment with depigmented-polymerized house dust mite (dpg-pol HDM) allergen extract in adults with asthma and/or rhinoconjunctivitis. METHODS: Patients included in a double-blind placebo-controlled AIT study with dpg-pol HDM allergen extract were reviewed at completion of the perennial treatment and 10-year follow-up (10y-FU). Change in symptom and rescue medication score was the primary objective. Visual analog scale (VAS), asthma control test (ACT), and degree of disease control were the secondary objectives. A comparative analysis between patients who underwent AIT treatment for <3 years and ≥3 years was performed. RESULTS: Data from 31 patients (mean age 38 years) were available at 10y-FU. All had asthma and 29 had rhinoconjunctivitis at baseline. Twenty-three patients were treated ≥3 years and 8 for <3 years. Seventeen (55%) patients were asymptomatic at completion of AIT, with significant differences for nasal, conjunctival, and bronchial symptoms (p < .0001) compared with baseline only in those patients treated ≥3 years. Nine (52.9%) patients remained completely asymptomatic at 10y-FU, all were treated for ≥3 years. Moreover, significant reduction in the number of patients with rhinitis (p = .0117), conjunctivitis (p < .0001), and bronchial (p = .0005) symptoms was observed at 10y-FU compared with baseline only in the ≥3 years treated. Ten (32.3%) patients did not require any rescue medication at 10y-FU, all had been treated for ≥3 years. ACT at 10y-FU showed a good control of asthma (median 23.5; 95% IC[22.0, 25.0]). No significant differences were observed between VAS at end of treatment compared with VAS at 10y-FU. CONCLUSIONS: Sustained clinical efficacy is achieved 10 years after completion of depigmented-polymerized HDM, however, these findings were observed only if patients are treated for at least 3 years.

Real-World Safety and Efficacy Clinical Data of an Improved Allergen-Specific Immunotherapy Product for the Treatment of Bee Venom Allergy.

The aim of this study is to explore the safety and efficacy of bee venom immunotherapy without HSA, in real-life patients. Methods: This is an observational retrospective study developed in seven hospitals in Spain, where patients treated with this immunotherapy were included. They gathered the protocol used to initiate the immunotherapy, adverse reactions, field re-stings, and the patient clinical data (clinical history, biomarkers, and skin prick test). Results: A total of 108 patients were included. In total, 4 protocols were used (5 weeks reaching 200 µg, and 4, 3, and 2 weeks reaching 100 µg). An incidence of systemic adverse reactions for each 100 injections of 1.5, 1.7, 0, and 0.58, respectively, was found. The demographic data showed not to directly affect the appearance of adverse reactions, except for those having a grade 2 systemic reaction with immunotherapy previously had a grade 4 systemic reaction; the IgE to Apis mellifera was 3 times higher in patients with systemic reactions of grade 1 than in the general group, and other specific IgEs were lower in those with systemic reactions. Most of the patients recognized Api m 1 followed by Api m 10. In the sample, 32% experienced spontaneous re-stings, without presenting systemic reactions, after a year of treatment.

Interactive Web-Based Resource for Annotation of Genetic Variants Causing Hereditary Angioedema (HADA): Database Development, Implementation, and Validation.

BACKGROUND: Hereditary angioedema is a rare genetic condition caused by C1 esterase inhibitor deficiency, dysfunction, or kinin cascade dysregulation, leading to an increased bradykinin plasma concentration. Hereditary angioedema is a poorly recognized clinical entity and is very often misdiagnosed as a histaminergic angioedema. Despite its genetic nature, first-line genetic screening is not integrated in routine diagnosis. Consequently, a delay in the diagnosis, and inaccurate or incomplete diagnosis and treatment of hereditary angioedema are common. OBJECTIVE: In agreement with recent recommendations from the International Consensus on the Use of Genetics in the Management of Hereditary Angioedema, to facilitate the clinical diagnosis and adapt it to the paradigm of precision medicine and next-generation sequencing-based genetic tests, we aimed to develop a genetic annotation tool, termed Hereditary Angioedema Database Annotation (HADA). METHODS: HADA is built on top of a database of known variants affecting function, including precomputed pathogenic assessment of each variant and a ranked classification according to the current guidelines from the American College of Medical Genetics and Genomics. RESULTS: HADA is provided as a freely accessible, user-friendly web-based interface with versatility for the entry of genetic information. The underlying database can also be incorporated into automated command-line stand-alone annotation tools. CONCLUSIONS: HADA can achieve the rapid detection of variants affecting function for different hereditary angioedema types, and further integrates useful information to reduce the diagnosis odyssey and improve its delay.

Outcome of 490 Desensitizations to Chemotherapy Drugs with a Rapid One-Solution Protocol.

BACKGROUND: Hypersensitivity reactions to chemotherapy drugs are quite frequent. Desensitization for chemotherapy drugs has become an option to maintain first-line therapy in patients who have suffered such reactions. OBJECTIVE: The objective of this study was to describe our experience in desensitization with antineoplastic agents using a rapid 1-solution protocol. METHODS: We performed a 3-year prospective observational study recording all patients who were desensitized with this protocol. All patients signed an informed consent. Skin test was performed at concentrations previously described as nonirritant. Desensitization was performed using only 1 solution of the drug prepared following the manufacturer instructions. Most drugs were diluted in a volume of 500 mL. We started infusion at 5 mL/h and increased doses at 15-minute intervals to 10, 25, 50, 75, and 100 mL/h. If no reaction occurred, and if the pharmacokinetics of the drug allowed it, we stepped up to 150, 200, and 250 mL/h. RESULTS: Ninety patients were desensitized to 93 drugs: oxaliplatin (30), carboplatin (16), paclitaxel (19), docetaxel (6), cetuximab (5), rituximab (6), and others (11). A total number of 490 procedures were performed. Sixteen patients (17.77%) presented 26 reactions (5.3%). Most reactions appeared in patients who were desensitized to platins and in patients with severe reactions. All but 3 cycles were completely administrated. No deaths or hospital admissions were recorded. CONCLUSIONS: This 1-solution protocol for desensitization has demonstrated to be safe and useful in our study population, especially for mild-to-moderate reactions and nonplatinum drugs. If our results were reproducible in other centers and larger populations, they could contribute to simplifying protocols and making desensitization available for more patients.

Savings associated with high-dose hypoallergenic house dust mite immunotherapy in rhinitis and/or asthma patients in Spain.

OBJECTIVES: To quantify the cost difference between conventional symptomatic treatment of mite allergy and specific subcutaneous immunotherapy (SCIT). METHODS: Observational, retrospective, and multicenter study was carried out in Spain in 2013. The medical records of 419 patients diagnosed with rhinitis and/or bronchial asthma for mite allergy were retrieved. Mean age was 24.9 years (standard deviation 14.4). The use of symptomatic medication (rescue and daily), diagnostic tests, unscheduled medical care, and sick leave days associated with SCIT treatment versus no-SCIT treatment was compared. Also measured was the SCIT treatment to no-SCIT treatment costs ratio: used resources (symptomatic medication, unscheduled medical care, diagnostic tests, and 3 years SCIT treatment and sick leave days) were quantified in euros. Efficacy (decreased resource usage) of first-year treatment was assumed during the remaining 2 years and also during the 3-year follow-up period. RESULTS: After a single year of SCIT, all quantified resources diminished significantly (P<0.05) from baseline. Estimated reduction in cost items included hospital resources (100% in hospitalizations, 82% in visits to the allergist, and 79% in emergency room visits), therapies (56% in rescue medication and 63% in daily medication), diagnostic tests (77%), and sick leave days (94%). Ratio of comparative calculation described as SCIT treatment versus non-SCIT treatment (or conventional symptomatic treatment) is 0.8. CONCLUSION: Direct costs are reduced by 64% and indirect costs by 94%. SCIT of hypoallergenic preparation of dust mite (Acaroid(®)) allows cost savings versus conventional treatment. Estimated savings for the public National Health System are 5.7 times the cost of immunotherapy.

Assessing the validity of asthma associations for eight candidate genes and age at diagnosis effects.

BACKGROUND: Before the advent of genome-wide association studies (GWAS), ADAM33, ADRB2, CD14, MS4A2 (alias FCER1B), IL13, IL4, IL4R, and TNF constituted the most replicated non-HLA candidate genes with asthma and related traits. However, except for the IL13-IL4 region, none of these genes have been found in close proximity of genome-wide significant hits among GWAS for asthma or related traits. Here we aimed to assess the reproducibility of these asthma associations and to test if associations were more evident considering the effect of age at diagnosis. METHODOLOGY/PRINCIPAL FINDINGS: We systematically evaluated 286 common single nucleotide polymorphisms (SNPs) of these 8 genes in a sample of 1,865 unrelated Spanish individuals (606 asthmatics and 1,259 controls). We found that variants at MS4A2, IL4R and ADAM33 genes demonstrated varying association effects with the age at diagnosis of asthma, with 10 SNPs showing study-wise significance after the multiple comparison adjustment. In addition, in silico replication with GWAS data supported the association of IL4R. CONCLUSIONS/SIGNIFICANCE: Our results support the important role of MS4A2, IL4R and ADAM33 genes in asthma and/or atopy susceptibility. However, additional studies in larger samples sets are needed to firmly implicate these genes in asthma susceptibility, and also to identify the causal variation underlying the associations found.

Successful management of mite-allergic asthma with modified extracts of Dermatophagoides pteronyssinus and Dermatophagoides farinae in a double-blind, placebo-controlled study.

BACKGROUND: Mite sensitivity is highly prevalent in tropical and subtropical regions, such as the Canary Islands. OBJECTIVES: To evaluate the clinical efficacy and safety of a depigmented polymerized allergen vaccine containing a 50% mixture of Dermatophagoides pteronyssinus and Dermatophagoides farinae. METHODS: Sixty-four patients participated in the study. It was prospective, double-blind, and placebo-controlled, with random allocation of patients to receive active treatment or placebo. The active group received a mixture of modified allergen extracts containing 50% D pteronyssinus and 50% D farinae; the control group received placebo. All individuals were diagnosed with mild/moderate asthma and rhinoconjunctivitis caused by sensitization to D pteronyssinus and D farinae. Bronchial provocation test (BPT) was considered the main outcome to document clinical efficacy. RESULTS: Fifty-four patients completed the study. The active group experienced a significant improvement in BPT (P < .001), whereas the placebo group did not (P = .648). At the end of the study, 20 patients in the active versus 9 in the placebo group (P = .013; odds ratio, 5.71 [1.76, 18.51]) needed more than twice the amount of allergen to obtain a positive BPT. The median improvement in the active group over placebo was 53.76% in total symptom and 58.09% in medication scores. CONCLUSION: Immunotherapy with a mixture of modified allergen extracts of D pteronyssinus and D farinae is safe and efficacious to treat mite-allergic asthma. CLINICAL IMPLICATIONS: This immunotherapy modifies the natural course of the illness because it improves all clinical outcomes measured and prevents the worsening of specific bronchial hyperreactivity.