Journal of Allergy and Clinical Immunology-In Practice最新文献

Background: Transient and usually asymptomatic increase in blood eosinophil count (BEC) associated with dupilumab treatment has been described. Predicting factors related to BEC increase and symptoms occurrence are still poorly investigated.

Objective: To investigate frequency, timing, duration, clinical relevance and potential predictors of BEC increase in a real-life multicentre cohort of patients affected by asthma and/or chronic rhinosinusitis with nasal polyps (CRSwNP) treated with dupilumab.

Methods: BEC and clinical conditions at baseline and every 3 months after dupilumab treatment start were assessed. Any adverse drug reaction was also recorded. Remission of dupilumab-associated eosinophilia was defined by follow-up BEC values < 0.5 x10ˆ9 cells/L.

Results: Overall, 108 out of 195 (55%) patients experienced an increased BEC after dupilumab initiation but only 29 out of 195 (14.9%) showed hypereosinophilia. BEC peak occurred 6 months after the treatment start and resolved after 9 months (median time). Probability of developing hypereosinophilia was 3.3 times higher in patients with baseline BEC between 0.5 and 1.5 cells x 10⁹L. Symptoms occurrence during BEC peak was higher in patients with comorbidities and in patients showing any increase of BEC.

Conclusions: In a real-life setting dupilumab treatment in asthma and/or CRSwNP patients was often associated with transient BEC increase but hypereosinophilia rarely occurred. Onset of symptoms co-occurring with BEC peak was observed in a minority of subjects. BEC should not preclude itself dupilumab initiation or continuation but deserves to be monitored for at least 8 months after the treatment start, particularly in the case of baseline eosinophilia/hypereosinophilia and/or comorbidities.

Background: The pivotal phase 3 EPITOPE trial, a 12-month, double-blind, placebo-controlled study of epicutaneous immunotherapy with the VIASKIN® patch containing 250 μg peanut protein (VP250) previously reported significant treatment response vs placebo in peanut-allergic toddlers aged 1-through-3 years.

Objective: To assess interim efficacy and safety of VP250 from the first year of the EPITOPE open-label extension (OLE) study.

Methods: Eligible participants enrolled in the OLE study for up to 3 years of total treatment with annual double-blind, placebo-controlled food challenges (DBPCFC) and safety assessments; here we report the first year OLE (Year 2) results.

Results: 266 EPITOPE participants enrolled in the OLE study; 244 underwent Month 24 DBPCFC (n=166 VP250; n=78 placebo). After 24 months of VP250, 81.3% reached an eliciting dose (ED) ≥1000 mg, 63.8% reached an ED ≥2000 mg, and 55.9% completed the DBPCFC (cumulative dose: 3444 mg) without meeting stopping criteria. No treatment-related anaphylaxis or serious treatment-related adverse events occurred during Year 2 in this treatment arm. Local application-site reactions occurred less frequently in Year 2 vs Year 1. In placebo-treated EPITOPE participants, outcomes after 1 year of open-label VP250 were consistent with EPITOPE treatment results: 62.7% reached an ED ≥1000 mg, 36.5% reached an ED ≥2000 mg, and 28.4% completed the DBPCFC without meeting stopping criteria; and there was 1 treatment-related anaphylaxis event.

Conclusions: Two years of VP250 in young peanut-allergic children demonstrated continued treatment effect increases without new safety signals. This supports the potential of VP250 as a safe and effective treatment for peanut allergy in young children.

Background: α₁-antitrypsin deficiency is caused by rare pathogenic variants in SERPINA1, the strongest genetic risk factor for COPD. Few studies have evaluated the effects of SERPINA1 variation on asthma severity accounting for critical gene-by-environment interactions with smoking.

Objective: To characterize the influence of SERPINA1 variation on asthma severity.

Methods: DNA samples from 847 non-Hispanic whites and 446 African Americans from the Severe Asthma Research Program underwent SERPINA1 resequencing to identify rare variants. An independent population of 1,955 individuals with asthma and α₁-antitrypsin concentrations from a Cleveland Clinic Health System (CCHS) database were evaluated for severity measures.

Measurements and main results: In whites, a history of minimum smoking significantly interacted with SERPINA1 low-to-rare frequency variation to determine risk for asthma-related healthcare utilization. This was attributed to PI type Z heterozygotes (MZ, N=11) who had a higher frequency of ED visits (6 [54.5%] MZ heterozygotes, OR=7.60, 95%CI=1.71-39.7, p=0.010), hospitalization (5 [45.5%], OR=16.1, 95%CI=2.64-150.4, p=0.0050) in the past year, and lifetime ICU admissions (6 [54.5%], OR=12.5, 95%CI=2.44-75.6, p=0.0032) compared to 146 individuals without SERPINA1 variants (30 [20.5%] reporting ED visits, 17 [11.6%] hospitalization, 15 [10.3%] ICU admission). SERPINA1 variant-ever smoking interactions in African Americans for ED visits (p=0.069) related to four of six compound heterozygotes reporting an ED visit. In CCHS, α₁-antitrypsin concentrations were inversely associated with moderate-to-severe asthma risk (OR=0.97 per 10 mg/dL increase in α₁-antitrypsin, 95%CI=0.94-0.99, p=0.010) and exacerbations (OR=0.84 per 10 mg/dL, 95%CI=0.76-0.94, p=0.002).

Conclusions: SERPINA1 variation and α₁-antitrypsin concentrations impact asthma severity through gene-environment interactions with minimum smoking.

Background: Though multiple meta-analyses have evaluated the efficacy and safety of anti-IL5 monoclonal antibody therapy, few studies have made detailed, specific assessments of adverse events and infectious diseases (ID) adverse events.

Objective: To conduct a meta-analysis to evaluate the effect of anti-IL5 therapy on ID adverse events.

Methods: A meta-analysis was undertaken using 27 randomized, placebo-controlled phase 3 clinical trials. Detailed information on ID events was extracted, as well as study demographics. ID events were recorded as serious events and non-serious events as they appeared in the clinical trial record in clinicaltrials.gov. ID events were then classified into clinical and microbiologic groups.

Results: Anti IL-5 therapy significantly reduced serious bacterial infections [RR = 0.808, 95% CI = 0.667 - 0.978] and pneumonias [RR = 0.806, 95% CI = 0.650 - 0.998]. Anti-IL5 therapy also significantly reduced influenza infection [RR = 0.817, 95% CI = 0.674 - 0.991], sinusitis [RR = 0.807, 95% CI = 0.685 - 0.951], non-serious lower respiratory tract infections [RR = 0.787, 95 % CI = 0.656 - 0.943] and C.difficile infection (p=0.025). Non-serious gastroenteritis was increased in those on anti-IL5 therapy [RR = 1.754, 95% CI = 1.087 - 2.830].

Conclusions: Anti-IL5 therapy significantly reduces adverse events categorized as serious bacterial infections, pneumonia, influenza, non-serious lower respiratory tract infections and C.difficile infection. In the population of patients receiving anti-IL5 therapy, these effects may translate into substantial decreases in healthcare utilization.

Clinical implications: Oral immunotherapy to sesame with crushed sesame seeds and tahini can be a safe and effective way to manage patients with sesame allergy. Our results suggest that it may help these patients achieve sustained unresponsiveness.

Background: Peanut oral immunotherapy (POIT) has promising potential of disease-modification, but there are no studies to date evaluating high dose POIT leading to ad-lib consumption of peanut products, especially in children 6 months to 4 years of age.

Objective: To report real world outcomes of high-dose POIT in children age 6 months to 4 years of age, including adverse events, achievement of ad-lib consumption and the impact of age on these outcome measures.

Methods: Patients 6 months to 4 years of age with a diagnosis of peanut allergy (PA) were enrolled in a POIT protocol with goal dose of 3000 mg. Demographics, along with POIT and clinical outcomes 6 months after POIT are reported.

Results: Sixty children started POIT, with a median age of 16 months. Three (5%) were lost to follow up, and 6 (10%) discontinued POIT due to recurrent adverse events or inability to consume daily peanut protein. Fifty-one (85%) children completed POIT in a median of 7 months, and were consuming ad-lib peanut products for a duration of 6 months after completion of the POIT protocol. Sixteen (26.7%) children experienced a total of 22 adverse reactions during POIT. Initiating POIT prior to 24 months of age increased the likelihood of ad-lib peanut consumption by an odds ratio of 11.69 (1.19-114.31, p=0.035).

Conclusions: Our study demonstrates that high dose POIT in infants and toddlers is well tolerated, and can lead to ad-lib introduction of dietary peanut products into the diet, especially if initiated before two years of age.

Background: Atopic Dermatitis is a common chronic skin disease that involves frequent physician visits and often complex care plans. Despite the expanding therapeutic options, there is no existing decision aid to guide patients, families, and clinicians through treatment options.

Objective: Our objective was to develop an evidence-based decision aid that would be widely accepted for shared decision-making in pediatric atopic dermatitis.

Methods: Per rigorous international patient decision aid standards (IPDAS), the following steps were taken: 1) literature review; 2) focus groups with patients and caregivers; 3) expert interviews; 4) prototype creation, revision, and pilot testing in the clinic; and 5) in-clinic testing.

Results: Six focus groups provided insight into patient/parent preferences (n=32) regarding treatment experiences and preferences. Nine expert interviews revealed implementation strategies for shared decision-making, eliciting themes of communication, patient education, challenges to and supports for treatment adherence, useful materials/resources, and other strategies for success. Using content from literature review, patient/parent focus groups and expert interviews a draft decision aid was systematically created. Cognitive interviews (n=10) with patients/parents resulted in tool refinement. In-clinic testing demonstrated the tool was helpful, out of 10, an average±SD score 7.8±1.7 (n=18). A final decision aid was produced.

Conclusions: A decision aid for children with atopic dermatitis can be used for clinical encounters and has the potential to improve patient/family engagement in decision-making. Additionally, we include a worksheet on patient/parent values and an eczema action plan for implementation. Efficacy of this tool will be tested across populations in future studies.