Impact of COVID-19 in allergen immunotherapy: An Italian survey

Allergen immunotherapy (AIT) is a common treatment for patients with allergic asthma and allergic rhinoconjunctivitis. There is evidence that the COVID-19 pandemic could have altered the administration of AIT in patients in some countries, as the pandemic caused major limitations to healthcare access and delivery. The objective of this study was to evaluate the impact of the disruption imposed by the pandemic on the perceptions and administration of AIT therapies in Italy. An online survey was carried out among Italian allergists between 22 February 2021 and 12 April 2021. The results show that Italian physicians (N=66) did not consider that the COVID-19 pandemic presented an added risk to patients with allergic asthma or rhinitis receiving AIT. Although most treatments continued, there were reduced rates of AIT therapy initiations and sublingual AIT was favored over subcutaneous AIT (AU)

Venom Immunotherapy: From Proteins to Product to Patient Protection.

In this review, we outline and reflect on the important differences between allergen-specific immunotherapy for inhalant allergies (i.e., aeroallergens) and venom-specific immunotherapy (VIT), with a special focus on Venomil® Bee and Wasp. Venomil® is provided as a freeze-dried extract and a diluent to prepare a solution for injection for the treatment of patients with IgE-mediated allergies to bee and/or wasp venom and for evaluating the degree of sensitivity in a skin test. While the materials that make up the product have not changed, the suppliers of raw materials have changed over the years. Here, we consolidate relevant historical safety and efficacy studies that used products from shared manufacture supply profiles, i.e., products from Bayer or Hollister-Stier. We also consider the characterization and standardization of venom marker allergens, providing insights into manufacturing controls that have produced stable and consistent quality profiles over many years. Quality differences between products and their impacts on treatment outcomes have been a current topic of discussion and further research. Finally, we review the considerations surrounding the choice of depot adjuvant most suitable to augmenting VIT.

Subcutaneous Allergen Immunotherapy in Children: Real Life Compliance and Effect of COVID-19 Pandemic on Compliance.

BACKGROUND: Subcutaneous allergen immunotherapy (SCIT) is an effective treatment for allergic rhinitis, asthma, and venom allergy. Compliance is essential for SCIT to obtain maximal benefit as it is a long-term treatment. OBJECTIVES: This study aimed to determine the level of real-life SCIT compliance in pediatric patients and the associated factors. Additional aims were to determine how SCIT compliance was affected by the COVID-19 pandemic and why some patients dropped out SCIT. METHOD: Pediatric patients diagnosed with allergic rhinitis, allergic asthma, or venom allergy that received SCIT between September 2012 and July 2020 were analyzed. RESULTS: The study included 201 children (66.7% male) with a median (interquartile range) age of 12.8 years (9.4-15.2) at the time of the first SCIT injection. The overall compliance rate before COVID-19 pandemic was 86.1%. Short SCIT follow-up time and venom anaphylaxis were found to be risk factors for drop out. The leading causes of drop outs were moving to another city/country (32.1%), symptom improvement (17.8%), treatment ineffectiveness (14.2%), and adverse reactions (14.2%). Among the 108 patients that were still receiving SCIT during the COVID-19 pandemic, 31 (28.7%) dropped out the therapy. The most frequent reasons for drop-out were fear of being infected with COVID-19 (35.4%) and thinking that the AIT practise stopped due to COVID-19 pandemic (29%). Male gender and older age were found to be the independent risk factors for drop-out of SCIT. CONCLUSIONS: Real life compliance in children was found 13.9% and it was higher than adults. Nearly one-third of children dropped out during the CO-VID-19 pandemic. Male gender and older age are associated with SCIT drop-out during the COVID-19 pandemic.

Allergen-specific subcutaneous immunotherapy-pain evaluation in pediatric age.

BACKGROUND: Allergen-specific immunotherapy is a potentially disease-modifying therapy that is effective for the treatment of patients with allergic diseases. Although the pain caused by the administration of subcutaneous immunotherapy with allergens (SCITA) is considered to be minimal, no studies assessing that pain for the treatment of only pediatric patients have been reported. Objectives: This research aimed to evaluate the pain associated with SCITA for pediatric patients followed at our Immunoallergology Department. METHODS: During four consecutive weeks, the nurse who administered the injection completed a questionnaire recording the child's assessment of the pain associated with SCITA; these questionnaires were randomized before any analyses were done. Two different pain evaluation scales were used, with the choice of scale being determined based on the child's age: the self-reporting faces scale (score: 0-10; 5 to 8 years old) and the numeric scale (score: 0-10; >8 years old). Demographic and clinical data, as well as any adverse reactions, were documented. RESULTS: We included 46 pediatric patients (mean age: 12.3 ± 2.6 years; 69.5% male), most of whom were suffering from rhinitis/rhinoconjunctivitis and undergoing subcutaneous immunotherapy with mites. Seven local adverse reactions were recorded, and all were mild. Ten patients did not mention any pain associated with SCITA. Of the 36 patients who mentioned some pain, 33 mentioned mild pain (scores between 1 and 3); only three mentioned moderate pain (scores between 4 and 6). For both scales, the median score obtained was 1. The maximum pain reported had a score of 6. No significant differences were observed between different groups of patients. CONCLUSIONS: In this study, SCITA was shown to be a mildly painful procedure that is associated with only a few local reactions. Therefore, SCITA should be considered as a safe option for the treatment of most pediatric patients suffering from allergies.

Real-world mapping of allergy immunotherapy in the United States: The argument for improving adherence.

Background: There is a dearth of real-world evidence studies focused on allergy immunotherapy (AIT) use among patients with allergic rhinitis (AR). Objective: This study examined claims data of AR patients residing in the United States to assess patient characteristics and health outcomes. Methods: AR patients were identified in the IBM MarketScan database between January 1, 2014, and March 31, 2017. Patients receiving AIT were identified with relevant billing codes (earliest AIT claim for vaccine as the index date); patients without AIT were identified with claims that contained a diagnosis code for AR (earliest AR claim as the index date). All the patients were required to have continuous enrollment 12 months prior to and following their index date. AIT patients reaching 25+ injection claims were analyzed as a separate maintenance cohort. Patients were assessed for demographic characteristics, comorbid conditions, and health care utilization. Results: A total of 2,334,530 AR patients were included; 103,207 had at least one AIT claim, with 45,279 (43.9%) of these patients reaching maintenance. Patients who reached AIT maintenance presented higher rates of baseline comorbidities than both the full AIT cohort and the patients with no AIT claims, including asthma (34.6% versus 30.1% versus 7.5%) and upper respiratory tract infections (63.1% versus 60.3% versus 34.2%). From baseline to follow-up, maintenance AIT patients demonstrated reductions in all AR-related comorbidities assessed, along with reductions in all-cause and AR-related service utilization. Conclusion: Patients initiating AIT presented the greatest need for therapeutic intervention, as evidenced by higher allergy-related comorbidities; those who reached maintenance demonstrated improved outcomes following the initiation of therapy. Continued efforts to increase patient awareness and adherence to AIT are needed.

Sulfadiazine Hypersensitivity and Desensitization in Children With Congenital Toxoplasmosis: A Report on Two Cases.

Combination therapy for toxoplasmosis consists of sulfadiazine, pyrimethamine and leucovorin. Although sulfadiazine can cause hypersensitivity reactions, such as fever, rash and liver dysfunction, there is no consensus on an effective therapy for congenital toxoplasmosis (CTox) without sulfadiazine. We attempted desensitization to sulfadiazine in 2 patients with CTox and sulfadiazine hypersensitivity. Desensitization was achieved for 1 patient.

Quality of life of patients undergoing specific allergen immunotherapy in allergic rhinitis.

INTRODUCTION: Although allergic diseases have been known since antiquity, both their understanding and systematics came later. The World Allergy Organization (WAO) defines the phenomenon of atopy as a predisposition of a person or family to the uncontrolled synthesis and release of IgE antibodies. Allergic rhinitis (AR) is one of the most important clinical diseases of rhinitis (NN, rhinitis). AR significantly reduces the quality of life, tends to increase, and its consequences may be life-threatening diseases. OBJECTIVE: The aim of the study is to determine the quality of life of patients who underwent specific allergen immunotherapy in allergic rhinitis. MATERIAL AND METHODS: The study was conducted at the Center for Specialist Allergology in Lublin between October 2018 - February 2019. The study covered a group of 157 patients. The diagnostic method used was a questionnaire. The first research tool was own questionnaire consisting of 31 questions. The second tool was the standardized questionnaire, the Polish version of the SF-36 Quality of Life Questionnaire. RESULTS: Studies have shown statistically significant changes in the symptoms of before and after immunotherapy, which means improving the quality of life and reducing the severity of symptoms and problems of respondents after therapy. The respondents were not in the best of health (50%). Over 50% of respondents said that the immunotherapy process significantly reduced personal / family expenses for treatment associated with allergic rhinitis. CONCLUSIONS: The conducted process of specific allergen immunotherapy improved the quality of life of respondents by increasing awareness of the quality of life through the prism of health change in relation to the general indicator in the area of mental problems by reducing their nuisance value more than in the area of somatic symptoms.

Hymenoptera venom allergy among children in Italy: time for pediatricians to take action.

Hymenoptera venom allergy (HVA) is one of the most frequent causes of anaphylaxis following a bee, vespid or ant sting. Real-life data regarding the management of HVA in children are lacking. To address this unmet need, we carried out a survey defining the current management of HVA in children among pediatric allergists in Italy. Educational investments on the improvement of the management of pediatric patients with HVA are urgently needed, and our analysis represents a relevant instrument in targeting a roadmap with this aim. The time for pediatric allergists to take action has come, and a task force from the Rare Allergic Diseases Commission of the Italian Society of Pediatric Allergy and Immunology is working on the topic to improve pediatricians' knowledge and optimize the care of these patients.

Imported fire ant immunotherapy prescribing patterns in a large health care system during an 11-year period.

BACKGROUND: The first large-scale evaluation of prescribing patterns for imported fire ant (IFA) in a large US health care system was published by Haymore et al in 2009. In this first evaluation of prescriptions from 1990 to 2007, the most often prescribed maintenance IFA prescription was 0.5 mL of 1:200 wt/vol. OBJECTIVE: To provide an updated description of IFA prescribing patterns over the ensuing 11 years from same large health care system. METHODS: We reviewed 1349 new IFA prescriptions written from 2007 to 2018, from a large nationwide health care system, with primary end points being maintenance prescription strength and prescribing patterns. RESULTS: In comparison to the data published by Haymore et al in 2009, which reported that 17% of the prescriptions were written for 0.5 mL of 1:100 wt/vol maintenance, we found that 69% (95% CI: 66.4%-71.4%) of IFA prescriptions written in the past 11 years were for the maintenance concentration of 0.5 mL of 1:100 wt/vol. We further studied the linear trend over time of percentage of prescriptions written for individual concentrations and observed that the percentage of 1:100 wt/vol prescriptions increased 3.5% yearly (R2 = 0.68, P < .001) from 2007 (40.0%, 95% CI: 24.6%-57.7%) to 2018 (84.4%, 95% CI: 77.4%-89.5%). CONCLUSION: Our study shows significant improvement in the accuracy and precision of IFA immunotherapy dosing for patients with IFA hypersensitivity, with ascendancy of 0.5 mL 1:100 wt/vol as the predominant treatment dose. A total of 87% of patients within our study were treated within the parameter recommendations, a stark improvement from findings in the 2009 Haymore study.

Approach to Patients with Allergic Rhinitis: Testing and Treatment.

This article evaluates the role of allergen immunotherapy (AIT) in the treatment of allergic rhinitis (AR). AIT has been shown to be effective in treating AR symptoms with resultant improvements in overall quality of life, comorbid illnesses, and medication requirements. Persistent clinical benefits have been shown years after AIT treatment discontinuation. AIT may prevent the progression of AR to asthma. AIT may more cost-effective than pharmacotherapy. Multiple individual studies and systematic reviews provide strong evidence for the clinical effectiveness of AIT in the treatment of AR. Cost-effectiveness and disease modification of AIT compared with standard drug treatment are additional advantages.

Clinical Prognosis of Renal Retransplant Patients: A Single-Center Experience.

BACKGROUND: Retransplantation is a treatment option in patients with end-stage renal failure due to graft loss. Outcomes of these patients due to high immunologic risk remain unclear. The aim of this study was to evaluate outcomes of renal retransplantation patients retrospectively. METHODS: Renal retransplant patients in our unit were evaluated retrospectively between 2010 and 2018. Patients' demographic characteristics, primary diseases, the causes of prior graft loss, immunologic status, desensitization protocols, the induction and maintenance treatments, the complications during the follow-up period, numbers of acute rejections, and the clinical prognosis were all detected from the patients' files. RESULTS: We retrospectively evaluated 17 patients who underwent a second or third renal allograft. Of these, 16 received a second and the remaining 1 patient received a third renal allograft. Immunologically, all of the 17 patients had negative flow cytometry crossmatch, 1 patient had a positive complement-dependent cytotoxicity crossmatch (Auto 12%), 16 patients had positive panel reactive antibody, the median HLA-mismatch was 3.5, and the score of donor-specific antibody relative intensity score (RIS) was 6.4 ± 6.3. Ten pretransplant patients had desensitization treatment. While scores for HLA-MM and HLA-RIS in the patients who had a desensitization therapy were determined higher, no statistical difference was observed (respectively, P = .28 and .55). No acute rejection episode developed. BK virus DNA viremia was detected in 4 patients during the posttransplant 6th month. We observed no patient death or no graft loss during the follow-up period. CONCLUSION: Although the retransplant patients who had a graft loss previously have high immunologic risks, retransplantation is reliable in these patients, but they should be followed up carefully in terms of BKV nephropathy.

Renal Transplantation in High Immunological Risk Patients: A Single-Center Experience.

BACKGROUND: Renal transplantation (RT) in high-risk patients is increasingly performed due to an inadequate organ pool and increased rate of RT after a failed transplantation. Safety and prognosis of RT in such patients with high risk is an ongoing debate. Herein we aimed to present our single-center experience on RT of high-risk patients. METHODS: A total of 89 consecutive RT patients were included into this study in a 10-month period. Patients were divided into 3 groups: the low-risk group (n = 47) with negative panel reactive antibody (PRA), medium-risk group (n = 18) with positive PRA but mean fluorescence intensity (MFI) < 2000, and high-risk group (n = 24) with positive PRA and MFI >2000 or donor specific antibody (DSA) positivity. Groups were compared in terms of demographic features, serum creatinine levels, acute rejection rates, delayed graft function (DGF), and patient or graft loss. RESULTS: Age of the recipients were similar between the groups. Desensitization (7% vs 11% vs 42%, respectively, in low-, medium-, and high-risk groups; P = .001), plasmapheresis (6% vs 11% vs 46%, respectively, P < .001), and rituximab treatments (0% vs 0% vs 25%, respectively, P < .001) were significantly more frequently performed in high-risk patients. Serum creatinine levels at 1 month and 6 months after RT were similar between the groups (P = .43 and P = .71, respectively). Rates of acute rejection (6% vs 6% vs 16%, respectively, P = .52) and DGF (9% vs 11% vs 29%, respectively, P = .15) were similar between the groups. Frequencies of loss of patient or graft were also similar (0% vs 6% vs 4%, P = .15). CONCLUSION: RT may be successfully performed in high-risk patients without an increase in the risk of acute rejection, DGF, or patient/graft loss.

Does the Canadian allocation system for highly sensitized patients work?

PURPOSE OF REVIEW: The number of sensitized heart transplant candidates is rising. Highly sensitized patients are disadvantaged because they encounter longer waiting times to heart transplant. Strategies to reduce their waiting times include waitlist prioritization and desensitization therapies. The purpose of this review is to describe the listing category for highly sensitized patients in the Canadian allocation system, examine the advantages and limitations of this strategy and provide an approach to the management of the highly sensitized patient awaiting heart transplant. RECENT FINDINGS: Analysis of data from the United Network of Organ Sharing shows that the incidence of death or removal from the waitlist in patients listed for heart transplant increases as the calculated panel reactive antibody (cPRA) increases and is independent of medical urgency. In the Canadian allocation system, patients with cPRA more than 80% have a similar incidence of death on the waitlist as less sensitized patients, suggesting they survive to be transplanted. Furthermore, prioritizing and transplanting highly sensitized patients has been associated with acceptable post-transplant outcomes. SUMMARY: The Canadian allocation system prioritizes highly sensitized patients to increase equity and access to transplantation while maintaining good post-transplant outcomes. Not all highly sensitized patients can wait for an organ, even if prioritized. A pragmatic individualized approach would consider the medical stability of the patient, the likelihood of transplant with a negative crossmatch and then determine whether waitlist prioritization or desensitization is the more appropriate strategy.

Estimation of Health and Economic Benefits of Commercial Peanut Immunotherapy Products: A Cost-effectiveness Analysis.

Importance: Commercial epicutaneous peanut immunotherapy (EPIT) and peanut oral immunotherapy (POIT) may offer significant quality-of-life improvements for patients with peanut allergy, but the cost-effectiveness of commercial peanut immunotherapies is uncharacterized. Objective: To evaluate critical inputs associated with the cost-effectiveness of EPIT and POIT from a societal perspective. Design, Setting, and Participants: Economic evaluation in which microsimulations with Markov modeling were performed evaluating virtual children aged 4 years over an 80-year time horizon. The base-case costs included a caregiver-reported willingness to pay of $3839 annually for safe and effective food allergy treatment. Estimates of predictive biomarkers or oral challenges were incorporated after the first year of therapy with additional analyses of immunotherapy risk reduction of anaphylaxis and probability of sustained unresponsiveness (SU) to peanut after 4 years. Exposures: Children received EPIT, POIT, or no immunotherapy treatment (n = 10 000 per treatment strategy). Main Outcomes and Measures: Rates of therapy-associated adverse reactions and quality-of-life improvements associated with changes in eliciting or tolerated peanut doses were modeled along with quality-adjusted life-years (QALYs), anaphylaxis, therapy-associated anaphylaxis, and fatalities. Results: In the base-case analysis without SU to peanut, the EPIT strategy cost less than POIT (mean [SD] cost, $154 662 [$46 716] vs $163 524 [$56 800]) and had fewer total episodes of anaphylaxis (mean [SD], 1.33 [1.55] vs 3.83 [5.02] episodes) and fewer episodes of therapy-associated anaphylaxis (mean [SD], 0.62 [1.30] vs 3.10 [4.94] episodes) but had lower QALY accumulation (mean [SD], 26.932 [2.241] vs 26.945 [2.320] QALYs). The incremental cost-effectiveness ratio was $216 061 for EPIT and $255 431 for POIT. Models were sensitive to therapy cost, SU rates, health state utility, and risk reduction of anaphylaxis. With health state utility sensitivity analyses, the ceiling value-based cost (willingness-to-pay threshold $100 000/QALY) was between $1568 and $6568 for EPIT and between $1235 and $5235 for POIT. If high rates of SU to peanut can be achieved in longer-term models, EPIT and POIT could produce savings in terms of both cost and QALY. Conclusions and Relevance: In this simulated analysis, findings showed that EPIT and POIT may be cost-effective under some assumptions. Further research is needed to understand the degree of health state utility improvement associated with each therapy, degree of protection against anaphylaxis, and rates of SU.

Efficacy and tolerability of desensitization in the treatment of delayed drug hypersensitivities to anti-tuberculosis medications.

BACKGROUND: Delayed drug hypersensitivity to first-line anti-tuberculosis medication is a major challenge in tuberculosis treatment. OBJECTIVE: This study was performed to investigate the efficacy/tolerability of desensitization therapy in treatment of first-line anti-tuberculosis medication hypersensitivity and the usefulness of immunologic evaluation therein. METHODS: This study was conducted as a prospective, observational cohort study. Subjects who experienced hypersensitivity reactions, including maculopapular exanthema (MPE) and drug reaction with eosinophilia and systemic symptoms (DRESS), to first-line anti-tuberculosis medications (isoniazid [INH], ethambutol [EMB], rifampin [RFP], and pyrazinamide [PZA]) were enrolled. Patch, intradermal, lymphocyte transformation, and oral provocation tests were performed to determine culprit drugs, which were desensitized with rapid and graded challenge protocols. Breakthrough reactions (BTRs) during or after desensitization were assessed. RESULTS: In total, 31 desensitization treatments (INH, 8; EMB, 8; RFP, 11; PZA, 4) to 12 patients (8 with MPE and 4 with DRESS) were performed. The overall success rate of desensitization was 80.7%. All the study subjects except one completed the full course of anti-tuberculosis treatment. The overall BTR free rate was 64.5%. Sixteen (80%) treatments for MPE and four (36.4%) for DRESS were BTR free (P = 0.023). Drugs that were positive on any two of three immunologic studies showed significantly high BTR rates (P = 0.014), although this was not correlated with desensitization failure rate. CONCLUSION: Rapid desensitization therapy to multiple anti-tuberculosis medications for delayed drug hypersensitivity was safe and successful. Combination of multiple immunologic evaluations may predict BTR although it needs validation in larger studies.

Nationwide questionnaire-based survey of oral immunotherapy in Japan.

BACKGROUND: Clinical trials on oral immunotherapy (OIT) have been increasing for nearly a decade; however, several national guidelines do not recommend OIT as a standardized procedure. The aim of this study was to obtain insights into the current use and practice of OIT in Japan. METHODS: A first questionnaire was mailed to 524 training and teaching facilities of the Japan Pediatric Society. The first survey requested information on the implementation of OIT, whereas the second survey aimed to gather more detailed information on OIT, such as its safety. RESULTS: In total, 360 facilities (69%) responded to the survey; among them, 102 (28%) provided OIT to 7973 patients [1544 received OIT while hospitalized (inpatient OIT), whereas 6429 received OIT without hospitalization (outpatient OIT)]. Approval for OIT was obtained from an ethics committee or institutional review board in 89% and 31% of facilities for inpatient and outpatient OIT, respectively. In inpatient OIT, immediate allergic reactions requiring treatment occurred in 68% of patients while hospitalized, and in another 56%, following discharge. In contrast, 11% of patients developed immediate allergic reactions in outpatient OIT. Adrenaline injections at home were required in 2%. Sixteen patients developed adverse reactions other than immediate allergic reactions, among which eosinophilic gastroenteritis was most common. CONCLUSIONS: OIT is widely provided not only as clinical research but also as general practice in Japan. However, because there is a high risk of developing anaphylaxis at home, OIT should be conducted carefully as in a clinical research setting taking safety into consideration.

Baked milk tolerant patient: is there any special feature?

BACKGROUND: Determining whether patients with cow's milk allergy (CMA) can tolerate foods produced with baked milk could provide a better quality of life, a better prognosis, and an option for desensitization. OBJECTIVES: The aim of this study was to identify which patients over four years of age with persistent CMA could tolerate baked milk, to compare the clinical and laboratory characteristics of reactive and non-reactive groups and to describe their clinical evolution. MATERIALS AND METHODS: A cross-sectional study was conducted (January/13 to November/14) that included all the patients followed at a food allergy center who met the inclusion criteria. The patients underwent an oral food challenge (OFC) with a muffin (2.8g of cow's milk protein). To exclude cow's milk (CM) tolerance, the patients were subsequently challenged with unheated CM. RESULTS: Thirty patients met all the inclusion criteria. Fourteen patients (46.7%) were considered non-reactive to baked milk and reactive to unheated CM. When the groups that were reactive and non-reactive to baked milk were compared, no statistically significant differences in clinical features were found. The prick test for α-lactalbumin (p = 0.01) and casein (p = 0.004) and the serum specific IgE for casein (p = 0.05) presented statistical differences. After one year, none of the patients who were reactive to baked milk were ingesting CM, while 28% of the tolerant patients were consuming fresh CM (p = 0.037). CONCLUSIONS: Baked milk can be tolerated by patients with CMA, especially those with lower levels of casein and α-lactalbumin. This option can improve quality of life and accelerate tolerance

No disponible

[Placebo effect in clinical trials with allergen-specific immunotherapy with inhalant allergens]. / Placeboeffekt in Studien zur allergenspezifischen Immuntherapie mit Inhalationsallergenen.

Placebo effects play an important role in the treatment of allergic diseases. Therefore, in this study, we analysed the described effects of placebo in all double-blind placebo-controlled clinical trials of allergen-specific immunotherapy (ASIT) with inhalant allergens (birch, grass, house dust mites) listed in the tables (updated July 2016) attached to the German S2k guideline on allergen-specific immunotherapy in IgE-mediated allergic diseases. The most common placebo consisted of verum without allergen, but when the subcutaneous route was used, histamine was sometimes added. From the 33 studies analysed no conclusions could be drawn regarding the pure placebo effect. The symptom medication score (SMS) from an adequate baseline period was described in one single study. An untreated population was not included in any study. Indirect evidence points to substantial placebo effects in up to 77% of the subjects with respect to retrospective, subjective parameters. Well-known factors influencing the placebo effect such as age, gender, application route/composition of the placebo, individual and cultural differences, severity of symptoms at the beginning and the probability of receiving verum have not been addressed regarding ASIT and could not be estimated from available data. Taken together regarding ASIT the placebo effect has been investigated inadequately. In spite of significant expenditure of time and costs future ASIT studies should include assessment of the SMS in an adequate baseline period and preferably include an untreated trial arm. A better understanding of placebo effects in ASIT trials will improve the design of clinical trials and the assessment of therapeutic effects.

Compliance with allergen immunotherapy and factors affecting compliance among patients with respiratory allergies.

BACKGROUND: Allergen-specific immunotherapy (AIT) is safe and effective for the treatment of allergic rhinitis and allergic asthma. However, patient non-compliance is a major barrier to achieving optimal outcomes Objective: To determine the level of compliance among patients using AIT and to identify factors associated with non-compliance Methods: A retrospective analysis using questionnaires was conducted to study compliance among 236 patients with allergic rhinitis with or without asthma who began AIT in 2009 or 2010 Results: The compliance rates at 3 y were 58.7% among patients on subcutaneous immunotherapy (SCIT) and 11.6% among those on sublingual immunotherapy (SLIT). The mean durations of treatment with SCIT and SLIT were 31 (+/-18.3) and 15.9 (+/-14.7) months, respectively. The most common causes of non-compliance among patients on SCIT were the frequency of injections (82.2%), the duration of treatment (70.9%), and commuting to the Allergy Center (67.7%). Reasons for non-compliance among patients on SLIT were related to inconvenience (43.4%), improvement without treatment (30.2%) and perception of poor efficacy (25.0%) Conclusion: Compliance with AIT is low, but at 3 years, it was higher among patients on SCIT than among patients on SLIT. Reasons for non-compliance include difficulty adjusting to treatment protocols and a perception that the efficacy is low. Patient education regarding the treatment course and the slow effect, as well as the need for close follow up to effectively prevent and treat adverse reactions, are important factors for improving compliance and treatment outcomes.