BACKGROUND: Allergen immunotherapy (AIT) is the only causal treatment for respiratory allergy. Long-term real-life effectiveness of AIT remains to be demonstrated beyond the evidence from randomised controlled trials (RCTs).
METHODS: REACT (Real world effectiveness in allergy immunotherapy) is a retrospective cohort study using claims data between 2007 and 2017. Study eligibility was a confirmed diagnosis of allergic rhinitis (AR), with or without asthma, and AIT. To ensure comparable groups, AIT-treated subjects were propensity score matched 1:1 with control subjects, using characteristic and potential confounding variables. Outcomes were analysed as within (pre vs post AIT) and between (AIT vs control) group differences across 9 years of follow-up (ClinicalTrial.gov: NCT04125888).
FINDINGS: 46,024 AIT-treated subjects were matched with control subjects and 14,614 were included in the pre-existing asthma cohort. AIT-treated subjects were 29·5 (16·3) years and 53% were male. Compared to pre-index year, AIT was consistently associated with greater reductions compared to control subjects in AR and asthma prescriptions, including both asthma controller and reliever prescriptions. Additionally, the AIT group had significantly greater likelihood of stepping down asthma treatment (P <0·0001). In addition to the reduction in asthma treatment in the AIT group, a greater reduction in severe asthma exacerbations was demonstrated (P<0·05). Reductions in pneumonia with antibiotic prescriptions, hospitalisations, and duration of inpatients stays were all in favour of AIT.
INTERPRETATION: The study extends the existing RCT evidence for AIT by demonstrating longer-term and sustained effectiveness of AIT in the real world. Additionally, in patients with concurrent asthma, AIT was associated with reduced likelihood of asthma exacerbations and pneumonia.
FUNDING: The study was funded by ALK A/S.
Introduction: Atopic dermatitis (AD) is a chronic and relapsing inflammatory skin disease characterized by severe pruritus and eczematous skin lesions. Subcutaneous immunotherapy (SCIT) refers to repeated contact with gradually increasing doses of allergen extracts, which improve patient tolerance to such allergens and controls, or reduces allergic symptoms. This study aimed to explore the long-term efficacy and safety of SCIT for patients with AD sensitized to house-dust mite (HDM). Methods: We conducted a retrospective analysis of 378 patients with HDM-sensitized AD. Among these patients, 164 received SCIT plus pharmacotherapy for 3 years (SCIT group) and the other 214 patients received only pharmacotherapy (non-SCIT group). The scoring atopic dermatitis (SCORAD) and pruritus visual analog scale (VAS) scores, laboratory test results, and adverse effects were recorded. Results: The SCORAD and pruritus VAS scores significantly decreased in the SCIT group. Also, the SCIT group showed higher reduction ratios of SCORAD and pruritus VAS scores than those observed in the non-SCIT group at 3 years after treatment initiation. The risk of development of new sensitization was higher in the non-SCIT group than in the SCIT group (relative risk 1.92 [95% confidence interval {CI}, 1.30-2.85]; p < 0.05). The eosinophil count of the participants significantly differed in the complete response (CR) group (p < 0.05) but not in the non-CR group (p = 0.098). However, the serum total immunoglobulin E value was not significantly reduced (p = 0.204). Of 8421 injections given to the patients, 231 injections (2.74%) showed adverse effects during the treatment period. Conclusion: Three years of SCIT can significantly reduce the severity and pruritus of moderate-to-severe AD with HDM sensitization. Patients who are multisensitized can also benefit from HDM SCIT. Patients can achieve long-term effects, such as prevention of neoallergen sensitization and inhibition of the allergy march.
BACKGROUND: The objective of this study was to analyze the effectiveness of allergen immunotherapy (AIT) with an allergoid in the treatment of house dust mites (HDM)‐induced allergic rhinitis and/or asthma based on recent real‐life data. The outcomes were measured using asthma incidence and consumption of corresponding medications as the indicator of persisting symptoms. METHODS: In this retrospective cohort analysis of a German longitudinal prescription database, patients who received at least two relevant mite AIT prescriptions in two different successive seasonal cycles were compared with non‐AIT patients who received at least three symptomatic allergic rhinitis (AR) prescriptions in successive mite seasons. Study endpoints included AR progression, asthma progression, asthma occurrence, and therapy adherence. We used multivariate regression analyses to estimate the effects of AIT, adjusting for relevant variables. RESULTS: This study included 2350 patients receiving a mite allergoid and 64 740 control patients. After up to 6 years of follow‐up, patients treated with mite allergoid required significantly fewer AR and asthma prescriptions (59.7% vs 10.8%) than the control group, and the probability of asthma development was significantly lower. The adherence of patients receiving allergoid was 63.8% at the end of the second year and 38.6% at the end of the third year. CONCLUSIONS: This real‐world evidence confirms the good efficacy of subcutaneous AIT with HDM mite allergoid in the treatment of allergic rhinitis and/or asthma. Up to 6 years of follow‐up revealed significant effects in allergic rhinitis by measuring the number of AR medications and demonstrating significant reductions in asthma medications.
Treatment of high-risk infants with HDM SLIT during early life resulted in a trend for reduction in asthma rates mid-childhood. This may be a viable preventative therapy for childhood asthma.
BACKGROUND: Moderate‐to‐severe allergic rhinitis (AR) may increase the risk of developing or worsening asthma, whereas treatment of AR with subcutaneously or sublingual allergen immunotherapy (SLIT) may slow this progression. METHODS: In a retrospective real‐world analysis, prescription fulfilment data were gathered from French retail pharmacies between 1 March 2012 and 31 December 2016. Using linear regression analyses, patients having received at least two prescriptions of grass pollen SLIT tablets over at least 2 successive years were compared with control patients having received symptomatic medications only. RESULTS: A total of 1099 SLIT patients and 27 475 control patients were included in the main analysis. With regard to symptomatic AR medication dispensing, we observed a 50% decrease in the pre‐index/follow‐up ratio in the SLIT group, a 30% increase in the control group without age matching (P < 0.0001 vs SLIT) and a 20% increase in the control group with age matching (P < 0.0001 vs SLIT). During the follow‐up, 11 (1.8%) and 782 (5.3%) patients initiated asthma treatment in the SLIT and control groups, respectively. The relative risk of medication dispensing for new asthma was lower in the SLIT group (by 62.5% [29.1%‐80.1%] without age matching (P = 0.0025) and by 63.7% [31.5%‐80.7%] with age matching; P = 0.0018). SLIT was also associated with slower progression of asthma medication dispensing during the follow‐up period, relative to the control group (regression coefficient: −0.58 [−0.74 to 0.42] without age matching (P < 0.0001) and −0.61 [−0.76 to −0.46] with age matching; P < 0.0001). CONCLUSION: Prescription of grass pollen SLIT tablets reduced the dispensing of AR and asthma medications in real life.
BACKGROUND: Real-world evidence is sparse on the benefits of allergen immunotherapy [AIT; subcutaneous/sublingual immunotherapy (SCIT/SLIT)], the only disease-modifying intervention for allergic rhinitis (AR) with long-term efficacy. This real-life study evaluated the effect of six AITs (native pollen SLIT/SCIT, four allergoid SCITs) vs symptomatic medication use, on AR symptoms and asthma symptoms/onset, in patients with birch pollen-associated AR and/or asthma.
METHODS: In this retrospective cohort analysis of a German longitudinal prescription database, AIT patients received ≥2 successive seasonal treatment cycles; non-AIT patients had ≥3 AR prescriptions in three seasons or previous month. Patients were matched for: index year, age, gender, main indication at index, number of seasonal cycles within treatment period, baseline AR/asthma treatment prescriptions. Multiple regression analysis compared prescription data in AIT and non-AIT groups as proxy for clinical status/disease progression.
RESULTS: Up to 6 years of follow-up, significantly more AIT (65.4%) vs non-AIT (47.4%) patients were AR medication-free; odds ratio (OR) [95% confidence interval (CI)]: 0.51 [(0.48-0.54); P < 0.001] (28.6% covariate-adjusted reduction vs non-AIT; P < 0.001), and significantly more AIT (49.1%) vs non-AIT (35.1%) patients were asthma medication-free [OR (95% CI): 0.59 (0.55-0.65); P < 0.001] (32% reduction vs non-AIT; P < 0.001), or reduced existing asthma medication use (32% covariate-adjusted reduction vs non-AIT; P < 0.001). During treatment, new-onset asthma risk was significantly reduced in the AIT vs non-AIT group (OR: 0.83; P = 0.001).
CONCLUSIONS: Birch pollen AIT demonstrated real-world benefits up to 6 years post-treatment cessation through significantly reduced AR and asthma medication intake, and significantly decreased risk of new-onset asthma medication use on-treatment.
BACKGROUND: Allergy immunotherapy (AIT) is the only treatment for allergic rhinitis (AR) and/or allergic asthma (AA) with long-term efficacy. However, there are few real-life data on the progression of AR and/or AA in patients receiving AIT.
OBJECTIVES: To assess the real-world, long-term efficacy of grass pollen sublingual immunotherapy (SLIT) tablets in AR and their impact on asthma onset and progression.
METHODS: In a retrospective analysis of a German longitudinal prescription database, AR patients treated with grass pollen SLIT tablets were compared with a control group not having received AIT. Multiple regression analysis was used to compare changes over time in rescue symptomatic AR medication use after treatment cessation, asthma medication use, and the time to asthma onset in the two groups.
RESULTS: After applying all selection criteria, 2851 SLIT and 71 275 control patients were selected for the study. After treatment cessation, AR medication use was 18.8 percentage points lower (after adjustment for covariates, and relative to the pretreatment period) in SLIT tablet group than in the non-AIT group (P<.001). Asthma onset was less frequent in SLIT tablet group than in non-AIT group (odds ratio: 0.696, P=.002), and time to asthma was significantly longer (hazard ratio: 0.523; P=.003). After SLIT cessation, asthma medication use fell by an additional 16.7 percentage points (relative to the pretreatment period) in the SLIT tablet group vs the non-AIT group (P=.004).
CONCLUSIONS: Real-world treatment of AR patients with grass pollen SLIT tablets was associated with slower AR progression, less frequent asthma onset, and slower asthma progression.
BACKGROUND: Allergy immunotherapy targets the immunological cause of allergic rhinoconjunctivitis and allergic asthma and has the potential to alter the natural course of allergic disease.
OBJECTIVE: The primary objective was to investigate the effect of the SQ grass sublingual immunotherapy tablet compared with placebo on the risk of developing asthma.
METHODS: A total of 812 children (5-12 years), with a clinically relevant history of grass pollen allergic rhinoconjunctivitis and no medical history or signs of asthma, were included in the randomized, double-blind, placebo-controlled trial, comprising 3 years of treatment and 2 years of follow-up.
RESULTS: There was no difference in time to onset of asthma, defined by prespecified asthma criteria relying on documented reversible impairment of lung function (primary endpoint). Treatment with the SQ grass sublingual immunotherapy tablet significantly reduced the risk of experiencing asthma symptoms or using asthma medication at the end of trial (odds ratio = 0.66, P < .036), during the 2-year posttreatment follow-up, and during the entire 5-year trial period. Also, grass allergic rhinoconjunctivitis symptoms were 22% to 30% reduced (P < .005 for all 5 years). At the end of the trial, the use of allergic rhinoconjunctivitis pharmacotherapy was significantly less (27% relative difference to placebo, P < .001). Total IgE, grass pollen-specific IgE, and skin prick test reactivity to grass pollen were all reduced compared to placebo.
CONCLUSIONS: Treatment with the SQ grass sublingual immunotherapy tablet reduced the risk of experiencing asthma symptoms and using asthma medication, and had a positive, long-term clinical effect on rhinoconjunctivitis symptoms and medication use but did not show an effect on the time to onset of asthma.
BACKGROUND: Allergic rhinitis (AR) is a main risk factor for the development of asthma. Two randomized open-label trials indicated that allergy immunotherapy (AIT) prevents the onset of asthma in patients with AR. However, these trials have methodological limitations, and it is unclear to what extent this experimental efficacy translates into clinical effectiveness.
OBJECTIVES: We sought to investigate the effectiveness of AIT to prevent asthma in patients with AR.
METHODS: Using routine health care data from German National Health Insurance beneficiaries, we identified a consecutive cohort of 118,754 patients with AR but without asthma who had not received AIT in 2005. These patients were stratified into one group starting AIT in 2006 and one group receiving no AIT in 2006. Both groups were observed regarding the risk of incident asthma in 2007 to 2012. Risk ratios (RRs) were calculated with generalized linear models by using a Poisson link function with robust error variance and adjustment for age, sex, health care use because of AR, and use of antihistamines.
RESULTS: In a total of 2431 (2.0%) patients, AIT was started in 2006. Asthma was newly diagnosed from 2007-2012 in 1646 (1.4%) patients. The risk of incident asthma was significantly lower in patients exposed to AIT (RR, 0.60; 95% CI, 0.42-0.84) compared with patients receiving no AIT in 2006. Sensitivity analyses suggested significant preventive effects of subcutaneous immunotherapy (RR, 0.54; 95% CI, 0.38-0.84) and AIT including native (nonallergoid) allergens (RR, 0.22; 95% CI, 0.02-0.68). AIT for 3 or more years tended to have stronger preventive effects than AIT for less than 3 years.
CONCLUSION: AIT effectively prevents asthma in patients with AR in a real-world setting. Confounding by indication cannot be excluded but would lead to an underestimation of the true preventive effects of AIT.
BACKGROUND: Sublingual immunotherapy (SLIT) is recommended for allergic diseases. However, clinical studies containing evidence-based data of this treatment in young children, which is rarely reported in the literature, are needed. This study was designed to assess the efficacy and safety of SLIT in children, including very young children.
METHODS: Two hundred sixty-four children aged 3-13 years old (133 children, 3-5 years old) with Dermatophagoides farinae-induced allergic rhinitis with or without asthma treated by standard pharmacotherapy had randomly received either SLIT (SLIT group) or no SLIT (control group) for 12 months. Symptoms, medications, visual analog scale (VAS) and presence of adverse events (AEs) were assessed at monthly visits. Skin-prick test and Dermatophagoides farinae-specific IgE and IgG4 were measured before and after treatment.
RESULTS: Both treatments were effective in the global clinical scores during the first seven visits when compared with baseline (all, p < 0.01), and SLIT showed lower symptoms scores and VAS scores throughout this period (all, p < 0.01). These improvements continued until the later visits only in the SLIT group. Also, the asthma medication consumption was decreased by SLIT treatment only at the end of study (p < 0.01). The specific IgG4 was significantly increased after SLIT treatment when compared with the control group, but no significant change of specific IgE was observed in either groups. In the SLIT group, there was no significant difference between children less than or more than 5 years old in terms of clinical efficacy, onset of action, immunologic parameters, and safety. No severe systemic AEs were reported.
CONCLUSION: SLIT is effective and well-tolerated in children with allergic rhinitis 3-13 years old.
Allergen immunotherapy (AIT) is the only causal treatment for respiratory allergy. Long-term real-life effectiveness of AIT remains to be demonstrated beyond the evidence from randomised controlled trials (RCTs).
METHODS:
REACT (Real world effectiveness in allergy immunotherapy) is a retrospective cohort study using claims data between 2007 and 2017. Study eligibility was a confirmed diagnosis of allergic rhinitis (AR), with or without asthma, and AIT. To ensure comparable groups, AIT-treated subjects were propensity score matched 1:1 with control subjects, using characteristic and potential confounding variables. Outcomes were analysed as within (pre vs post AIT) and between (AIT vs control) group differences across 9 years of follow-up (ClinicalTrial.gov: NCT04125888).
FINDINGS:
46,024 AIT-treated subjects were matched with control subjects and 14,614 were included in the pre-existing asthma cohort. AIT-treated subjects were 29·5 (16·3) years and 53% were male. Compared to pre-index year, AIT was consistently associated with greater reductions compared to control subjects in AR and asthma prescriptions, including both asthma controller and reliever prescriptions. Additionally, the AIT group had significantly greater likelihood of stepping down asthma treatment (P <0·0001). In addition to the reduction in asthma treatment in the AIT group, a greater reduction in severe asthma exacerbations was demonstrated (P<0·05). Reductions in pneumonia with antibiotic prescriptions, hospitalisations, and duration of inpatients stays were all in favour of AIT.
INTERPRETATION:
The study extends the existing RCT evidence for AIT by demonstrating longer-term and sustained effectiveness of AIT in the real world. Additionally, in patients with concurrent asthma, AIT was associated with reduced likelihood of asthma exacerbations and pneumonia.
