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.

Health-related quality of life in children and adolescents after systemic sting reaction.

INTRODUCTION AND OBJECTIVES: Insect stings are the second trigger of anaphylaxis in children and adolescents, causing a potentially life-threatening reactions. Hence health-related quality of life (HRQoL) is an important issue for Hymenoptera venom allergy (HVA) patients. The aim of this cross-sectional study was to evaluate the impact of HVA on young patients' HRQoL, including their socio-demographic characteristics. MATERIAL AND METHODS: The study sample included 102 patients aged 8-17 (Mean 12.5 years, SD=3.0), who were under diagnosis or venom immunotherapy due to systemic reaction after an insect sting in one of the tertiary referential centers in Poland. They were mostly boys (70%), and mainly from rural areas (63%). HRQoL of studied patients was measured with the Children's Hymenoptera Venom Allergy Quality of Life Scale, a questionnaire covering 6 dimensions: anxiety, caution, limitations, discomfort, support received from parents and a feeling of safety, each measured from 1 to 5. Independent predictors of HRQoL were estimated using the Generalized Linear Model. RESULTS: In the group of children being dermal reactors, girls reported a higher level of anxiety (B=1.17, 95%CI=(0.30;2.03), p=0.008). In the group of children with grade 2 it was the girls who reported lower anxiety (B=-1.33, 95%CI=(-2.38;-0.29), p=0.013). Boys treated longer than 3 years had their level of anxiety significantly lower than those studied at diagnosis (B=-0.65, 95%CI=(-1.23;-0.07), p=0.028). The feeling of safety was higher in children living in villages than in those living in towns (B=0.30, 95%CI=(0.03;0.56), p=0.031). CONCLUSIONS: The gender, treatment duration and stage of anaphylactic reaction influenced level of anxiety. The level of feeling of safety was related to the place of living.

Changing Patient Mindsets about Non-Life-Threatening Symptoms During Oral Immunotherapy: A Randomized Clinical Trial.

BACKGROUND: Oral immunotherapy (OIT) can lead to desensitization to food allergens, but patients can experience treatment-related symptoms of allergic reactions that cause anxiety and treatment dropout. Interventions to improve OIT for patients are needed. OBJECTIVE: To determine whether fostering the mindset that non-life-threatening symptoms during OIT can signal desensitization improves treatment experience and outcomes. METHODS: In a randomized, blinded, controlled phase II study, 50 children/adolescents (28% girls, aged 7-17 years, M = 10.82, standard deviation = 3.01) completed 6-month OIT for peanut allergies. Patients and their parent(s) had monthly clinic visits at the Sean N. Parker Center for Allergy and Asthma Research between January 5, 2017, and August 3, 2017. All families received identical symptom management training. In a 1:1 approach, 24 patients and their families were informed that non-life-threatening symptoms during OIT were unfortunate side effects of treatment, and 26 patients and their families were informed that non-life-threatening symptoms could signal desensitization. Families participated in activities to reinforce these symptom mindsets. RESULTS: Compared with families informed that symptoms are side effects, families informed that symptoms can signal desensitization were less anxious (B = -0.46, 95% confidence interval [CI]: -0.76 to -0.16; P = .003), less likely to contact staff about symptoms (5/24 [9.4%] vs 27/154 [17.5%] instances; P = .036), experienced fewer non-life-threatening symptoms as doses increased (BInteraction = -0.54, 95% CI: -0.83 to -0.27; P < .001), less likely to skip/reduce doses (1/26 [4%] vs 5/24 [21%] patients; P = .065), and showed a greater increase in patient peanut-specific blood IgG4 levels (BInteraction = 0.76, 95% CI: 0.36 to 1.17; P < .001). CONCLUSIONS: Fostering the mindset that symptoms can signal desensitization improves OIT experience and outcomes. Changing how providers inform patients about non-life-threatening symptoms is a promising avenue for improving treatment.

Adherence to Subcutaneous Allergen Immunotherapy in Southeast Turkey: A Real-Life Study.

BACKGROUND Subcutaneous immunotherapy (SCIT) in allergic rhinitis (AR) and asthma is a very effective treatment, but adherence is still a serious problem. Studies addressing real-life adherence to SCIT are rare in the literature. The aim of this study was to evaluate the adherence to SCIT in AR and asthma. MATERIAL AND METHODS The medical records of patients prescribed SCIT for treatment of AR and/or asthma were evaluated. Patients who continued the SCIT treatment as prescribed were defined as adherent, patients who stopped the treatment before the recommended period were defined as nonpersistent, and those who never started the treatment were defined as primary poor adherence. Age, gender, residence, type of SCIT, comorbidities, occupation, income, and adverse reactions were evaluated between these groups. RESULTS Ninety-five patients prescribed SCIT for the treatment of AR and/or asthma formed our cohort (female/male: 51/44). The mean (SD) age and duration of SCIT were 32.2±10.0 (range, 17-63) years, 14.4±12.7 (1.0-58.5) months, respectively. Sixty-two (65.3%) patients were adherent, (28.4%) patients were nonpersistent, and 6 (6.3%) patients were primary poor adherent. Nineteen (21.4%) patients had local adverse reactions and one (1.1%) had anaphylaxis. There were no differences between groups for age, gender, residence, type of SCIT, comorbidities, income, or occupation. The most frequent reason of nonpersistence was the cost of treatment. CONCLUSIONS Our study found that adherence to SCIT is low in a real-life setting in southeast Turkey, similar to most previous adherence studies.

High adherence to subcutaneous immunotherapy in a real-life study from a large tertiary medical center.

BACKGROUND: Studies on real-life adherence to subcutaneous allergen immunotherapy (SCIT) for respiratory allergy are scarce. The aim of this study was to evaluate adherence to SCIT. METHODS: The patients prescribed SCIT for allergic rhinitis and/or asthma in 2009-2011 were contacted in 2014 and asked whether they completed at least the 3 years of SCIT and/or whether they suspended the treatment for at least 2 months. The Total Symptom Score-6, visual analog scale (VAS), asthma control test (ACT), medication scores, quality of life (QoL) scores, and immunotherapy satisfaction scores with VAS obtained before the initiation of SCIT in the first year and at the end of SCIT were compared. RESULTS: A total of 204 patients (136 female [66.7%]; mean age, 38.83 ± 12.02 years) were included; 73% (149/204) were both compliant and persistent; 14% (29/204) were only persistent; and, overall, 87.3% (178/204) were considered adherent. Adherence was more frequent in female patients (95% CI, 62.3-76.3%; p = 0.018). Medication, symptom, ACT, and QoL scores in the first year and at the end of the treatment were significantly lower than the initial scores, and the immunotherapy satisfaction scores at the end of treatment were higher than the scores in the first year in the patients who were adherent (p < 0.001 for each score). CONCLUSION: The adherence rate to SCIT in our study was relatively high, in contrast to previous real-life data. Results of our study indicated that a close relationship between allergists and their patients during SCIT and the follow-up period in the same center improved the outcome of SCIT.

Patient quality of life following induction of oral immunotherapy for food allergy.

BACKGROUND: Patient quality of life improves following successful completion of oral immunotherapy (OIT), but the process itself might have undesirable effects. We aimed to evaluate patient quality of life following OIT initial induction. METHODS: The Hebrew version of the Food Allergy Quality of Life Questionnaire-Parental Form (FAQLQ-PF) was validated and administered to the parents of children following the first week of OIT for food allergy (n = 119). Patient demographics and clinical history as well as the course of initial induction week were reviewed. RESULTS: Pre-OIT severity of food allergy, defined as severity of reactions due to accidental exposure to the allergenic food (anaphylactic reactions, p = 0.017; epinephrine use, p = 0.049; emergency room referrals p = 0.003; and hospital admissions, p = 0.015) and a lower number of tolerated doses during initial induction, reflective of a lower maximal tolerated dose for the different allergens (p = 0.011) were associated with worse total FAQLQ-PF scores. The number of tolerated doses during induction and pre-OIT emergency room referrals remained significantly associated with worse total score of the FAQLQ-PF on multivariate analysis (p = 0.016 and p = 0.005, respectively). The correlation between the number of tolerated doses and quality of life scores was moderate-strong primarily in children aged 6-12 years (Total score, r = -0.41, p = 0.001; Emotional Impact r = -0.42, p = 0.001; Food Anxiety, r = -0.38, p = 0.002; Social and Dietary Limitations, r = -0.33, p = 0.009). CONCLUSIONS: Pre-OIT reaction severity affects quality of life in both preschool and school-aged food-allergic children. In contrast, a lower maximal tolerated dose during OIT induction is associated with worse indices of quality of life primarily in children aged 6-12 years.

Non-adherence to subcutaneous allergen immunotherapy: inadequate health insurance coverage is the leading cause.

BACKGROUND: To sustain the long-lasting beneficial effects of subcutaneous allergen immunotherapy, the recommended duration of treatment is 3 to 5 years. Nevertheless, many patients discontinue allergy injections prematurely and therefore might not appreciate the full therapeutic benefit. OBJECTIVE: To examine factors leading to premature discontinuation of subcutaneous allergen immunotherapy (cessation before completion of the recommended duration). METHODS: Patients who discontinued immunotherapy before the completion of the prescribed duration and received their final injection from January 2008 through September 2013 were contacted to identify the reason for stopping the allergy injections. Phase of treatment (escalation or maintenance) was used to measure the duration of treatment at the time of cessation and patients were grouped accordingly. RESULTS: The study population consisted of 555 patients with allergic rhinitis and/or asthma who terminated immunotherapy prematurely. Two hundred thirteen (38%) were men and 342 (62%) were women. The following reasons were cited by patients for non-adherence to immunotherapy: requirement of copayment for allergy injections and/or payment for allergen extract by their health insurer (40%); inconvenience of travel (15%); change of residence (8%); concurrent health problems (5%); patient-perceived ineffectiveness (4%); patient-perceived lack of need to continue immunotherapy (2%); adverse effects from injection (local reaction 1%; systemic allergic reaction 0.5%); and trial of alternative medicine (0.1%). The remaining 24.4% did not provide a reason for discontinuation. CONCLUSION: Of the various factors, inadequate reimbursement for allergen extract and allergy injections by health insurers is the most common reason cited for non-adherence to subcutaneous allergen immunotherapy.

Patient initiation and persistence with allergen immunotherapy.

BACKGROUND: Allergen immunotherapy (AIT) is advised for patients with allergic rhinitis who remain symptomatic despite the use of pharmacotherapy and allergen avoidance. Several factors influence the decision to initiate and complete the AIT regimen. OBJECTIVE: To evaluate patient initiation and persistence with subcutaneous and sublingual immunotherapies (SCIT and SLIT) according to physician recommendation. METHODS: A retrospective review of electronic health records of patients with allergic rhinitis for whom AIT was recommended was conducted in a large private allergy practice in Pennsylvania. RESULTS: Of 8,790 patients advised to consider AIT, 36.2% initiated AIT (57% adults, 43% children); 78% chose SCIT and 22% chose SLIT drops. Election of AIT was significantly associated with select comorbidities, specifically chronic sinusitis (8.1% for AIT vs 10% for no AIT), allergic conjunctivitis (12.5% for AIT vs 18.5% for no AIT), and asthma (33.8% for AIT vs 37.4% for no AIT; P < .05). Choice of SCIT vs SLIT drops was significantly associated with older age, female sex, select comorbidities, and more allergy medications at initiation (P < .05). Of adults, 30.2% completed at least 3 years of recommended treatment. Median time on treatment was longer for adults on SCIT vs SLIT drops (3 vs 1.6 years). Similarly, 35.4% of children completed treatment, with a longer median time on treatment for SCIT (4.7 years) vs SLIT drops (3.5 years). CONCLUSION: A minority of patients initiated AIT according to allergist recommendation and a subset of these patients completed therapy. AIT might be an underused option that could benefit patients unable to manage allergic rhinitis symptoms by other means. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01549340.

Real-life compliance and persistence among users of subcutaneous and sublingual allergen immunotherapy.

BACKGROUND: Subcutaneous allergen immunotherapy (SCIT) and sublingual allergen immunotherapy (SLIT) are safe and effective treatments of allergic rhinitis, but high levels of compliance and persistence are crucial to achieving the desired clinical effects. OBJECTIVE: Our objective was to assess levels and predictors of compliance and persistence among grass pollen, tree pollen, and house dust mite immunotherapy users in real life and to estimate the costs of premature discontinuation. METHODS: We performed a retrospective analysis of a community pharmacy database from The Netherlands containing data from 6486 patients starting immunotherapy for 1 or more of the allergens of interest between 1994 and 2009. Two thousand seven hundred ninety-six patients received SCIT, and 3690 received SLIT. Time to treatment discontinuation was analyzed and included Cox proportional hazard models with time-dependent covariates, where appropriate. RESULTS: Overall, only 18% of users reached the minimally required duration of treatment of 3 years (SCIT, 23%; SLIT, 7%). Median durations for SCIT and SLIT users were 1.7 and 0.6 years, respectively (P < .001). Other independent predictors of premature discontinuation were prescriber, with patients of general practitioners demonstrating longer persistence than those of allergologists and other medical specialists; single-allergen immunotherapy, lower socioeconomic status; and younger age. Of the persistent patients, 56% were never late in picking up their medication from the pharmacy. Direct medication costs per nonpersistent patient discontinuing in the third year of treatment were €3800, an amount that was largely misspent. CONCLUSION: Real-life persistence is better in SCIT users than in SLIT users, although it is low overall. There is an urgent need for further identification of potential barriers and measures that will enhance persistence and compliance.

Patient knowledge, perceptions, expectations and satisfaction on allergen-specific immunotherapy: a survey.

BACKGROUND: Assessing patient's perspective provides useful information enabling a customized approach which has been advocated by current guidelines. In this multicentre cross-sectional study we evaluated personal viewpoints on allergen-specific immunotherapy (SIT) in patients treated with subcutaneous (SCIT) or sublingual (SLIT) immunotherapy. METHODS: A survey of 28 questions assessing patient's knowledge, perceptions, expectations and satisfaction was developed by an expert panel and was applied by physicians from allergology centres in patients with respiratory allergy treated with SIT. Treating physicians independently reported their satisfaction level regarding SIT for each patient. RESULTS: Fully completed surveys from 434 patients (55.3% male; 66.7% poly-sensitized, 74% SLIT) were analysed. Mean duration of SIT was 2.5 years with different allergens. Most patients acquired their SIT knowledge from their physician (95%) and consequently, their physicians' opinion in their choice to start with SIT was important. Most patients perceived SIT to be safe and easy to integrate into their daily routine. The main motivations for SIT were its supposed potential to alter the course of the disease (45.7%), less need of (28.2%), or dissatisfaction with current pharmacotherapy (19.3%). Both patients' and physicians' satisfaction was high (VAS-scores 74/100 and 78/100, respectively) and showed a significant correlation (SCIT: r=0.612; SLIT: r=0.608). No major difference was found in patients' answers based on the level of education. CONCLUSION: In this real life study evaluating different aspects of patient's perspective on SIT, the majority of patients had an adequate level of knowledge, perceptions, expectations and satisfaction about SIT, which corresponded well with the physician's perceptions and satisfaction. Our data warrant the use of patient's perspectives on chronic SIT treatment.

Barriers to implementing protocols for kidney paired donation and desensitization: survey of U.S. transplant programs.

CONTEXT: Special types of kidney transplant exist for patients who have willing but incompatible donors. Two types of transplants that circumvent donor-recipient incompatibility are "kidney paired donation" and "desensitization." Lack of access to these protocols limits living donations and shortens the life span of patients with willing but incompatible donors. OBJECTIVE: To understand potential barriers to implementing kidney paired donation and desensitization, as well as attitudes toward nondirected donation and compatible type O donation, which would maximize the number of kidney paired donation transplants performed via chains. DESIGN: We created a 56-question Web-based survey to elicit information from US transplant program directors about 24 potential barriers to implementing these protocols. PARTICIPANTS: Of 166 programs contacted, 96 responded, including 88 complete and 8 partial responses. After pediatric-only programs and multiple responses from the same program were removed, 84 total (78 complete) remained. MAIN OUTCOME MEASURES: Respondents were asked to designate each barrier as "major," "minor," or "not a barrier". RESULTS: Availability of dedicated nurse coordinators and the United Network for Organ Sharing's variance request process (although kidney paired donation does not actually require a variance) were significant barriers to kidney paired donation. Most respondents (54%, 42/78) would prefer to participate in a regional rather than a national protocol for kidney paired donation. Risk of complications was the most significant barrier to desensitization. University affiliation, region, and training (nephrologist vs surgeon) had little effect on perception of barriers. Most (92%, 71/78) would evaluate nondirected donations; 53% (41/78) would encourage compatible type O donors to enter kidney paired donation.

Parental perceptions in egg allergy: does egg challenge make a difference?

The aim of the study was to determine the effect of an oral egg challenge in egg sensitized children on parental perceptions relating to their child's allergy. A questionnaire was completed by parents for 167 children attending a tertiary paediatric clinic with egg sensitization. The questionnaires included 10 questions concerning parental perceptions of their child's egg allergy. Parental perceptions of those children who had not had an egg challenge (n = 83) were compared with those whose children had a positive (n = 27) and those with a negative (n = 57) egg challenge. A significant difference (p = < or =0.02) was observed between challenge positive(CP) and challenge negative (CN) subjects in reported changes to lifestyle and the fact that more parents in the CN group expected little or no future inconvenience for the child. The responses of parents whose child had undergone an egg challenge differed significantly (p = < or =0.005) from those not challenged with a significant reduction in the following parameters; the effect on out-of-home care arrangements, the perception of being more severe as compared to other common childhood illnesses, whether they found egg allergy to be moderately or very stressful, whether their lifestyle was changed, the expectation of little or no future discomfort for the child and whether others treated the child differently. The performance of an egg challenge was associated with reduced adverse parental concerns. For 6/10 parameters, expectations concerning egg allergy in children who had been challenged were significantly better than those who had never been challenged irrespective of the challenge outcome. The greater certainty provided by the performance of a food challenge may be a positive outcome in both CP and CN children.

Comparison between continuous or intermittent schedules of sublingual immunotherapy for house dust mites: effects on compliance, patients satisfaction, quality of life and safety.

Sublingual immunotherapy (SLIT) is indicated in the treatment of allergic rhinitis and asthma. However, an issue scantly investigated is the patients satisfaction and the consequent compliance. This study is aimed at evaluating the possible differences of SLIT administered continuously or intermittently on several parameters: clinical efficacy, Quality of Life (QoL), satisfaction, compliance and safety. Forty allergic patients were treated for 12 months. The treatment was carried out by sublingual administration of an allergen extract of a 50% mixture of Dermatophagoides pteronyssinus and Dermatophagoides farinae at 10 and 300 IR/ml concentrations. Patients were randomly treated continuously or intermittently (i.e. 2 month treatment alternate to 2 month suspension). Both schedules were significantly effective in reducing allergic symptoms and improving QoL. Compliance and satisfaction were good in both groups. Local and systemic reactions were few, self-resolving, and mild in both schedules. Intergroup analysis did not reveal any difference between the two groups regarding these parameters. In conclusion, this preliminary study provides the evidence that also intermittent SLIT is as effective and safe as traditional continuous treatment. In addition, compliance and satisfaction are super-imposable in the two groups.

Outcome survey of insect venom allergic patients with venom immunotherapy in a rural population.

BACKGROUND: Hymenoptera venom anaphylaxis is a frightening event that affects physical and psychical functioning. PATIENTS AND METHODS: Retrospective survey of 182 Hymenoptera venom allergic patients living in a rural area using a questionnaire targeting on patients' satisfaction during therapy, fear of anaphylactic recurrences and changes in lifestyle before and after venom immunotherapy (VIT). Additionally, patients' self-assessment of quality of life, daily outdoor time and re-sting rate were recorded. RESULTS: 146 patients returned the questionnaire (58.9% male, 41.1% female, 25.3% honey bee allergic, 67.8% wasp allergic, 41.1% re-sting rate, mean follow-up time 6.5 years). Measurement of the parameters fear, satisfaction and changes in lifestyle revealed a significant improvement after VIT. This correlated with the patients'self-assessment of quality of life,when 89.7% declared an improvement after VIT. Although the improvement was higher in patients with re-stings, also patients without re-stings clearly benefited from VIT. Interestingly, females were significantly more affected by Hymenoptera venom allergy than males,whereas both genders showed a similar improvement after VIT. CONCLUSIONS: Patients with Hymenoptera venom sting allergy significantly benefit from VIT in regard to both biological and psychological outcome. VIT should still be provided to all Hymenoptera venom allergic patients as standard of care.

Factors affecting compliance with allergen immunotherapy at a military medical center.

BACKGROUND: Allergen immunotherapy (AIT) is a safe and effective treatment for certain allergic disorders; however, noncompliance with therapy is common. We evaluated the compliance rates among groups receiving AIT at a military medical center and identified factors affecting compliance. METHODS: The charts of the 381 actively enrolled patients in our AIT program were evaluated for patient compliance. Noncompliant patients were contacted to determine the reason for stopping therapy. Patients were then grouped by diagnosis, age, sex, military status, and schedule of AIT and evaluated for differences. RESULTS: The overall compliance rate was 77.4%. The most common reasons for noncompliance included inconvenience, precluding medical condition, and adverse systemic reaction. There were no differences in compliance rates by diagnosis or sex. Noncompliant patients were younger than compliant patients, 35.4 years versus 42.4 years (P = 0.001); however, when patients were divided into three age categories (<18, 18 to 45, and >45 years), the youngest and oldest groups were more compliant (P < 0.001). Active-duty members were less compliant than retirees and family members, 65.7% versus 83.1% and 81.4%, respectively (P = 0.004). Patients receiving a conventional schedule of AIT were more compliant than those on a rush schedule, 80.0% versus 48.4% (P < 0.001). CONCLUSIONS: Factors found to affect patient compliance with an AIT regimen at our military medical center include age, military status, and schedule of AIT. The most common reasons for noncompliance included inconvenience, precluding medical conditions, and adverse systemic reactions. Clinicians need to be aware of the factors limiting patient compliance with AIT in an attempt to maximize treatment effectiveness.