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Issue #6, August 2021
Welcome back to The Buzz, a monthly feature of the HIVE community where we summarize recent articles with high clinical relevance for Canadian allergists, immunologists and dermatologists. View archived issues of The Buzz at thehivecommunity.org/the-buzz
In Issue #6 of The Buzz, we highlight five new publications.
Seroconversion following vaccination for patients on anti-CD20 therapy
Anti-CD20 therapy depletes peripheral B cells, however, the effect of treatment on B cells located in peripheral lymphoid tissues is less clear. There is less of effect on memory B cells and plasma cells as they do not express the CD20 antigen. With the COVID-19 vaccination program underway, Vijenthira and colleagues sought to characterize the effect of anti-CD20 therapy on markers of vaccine responsiveness using a systematic literature review. Outcomes to influenza vaccination are standardized, so a metaanalysis was possible with the influenza vaccine data. Thirty-eight studies comprising 905 patients were included in the systematic review.
Patients who received anti-CD20 therapy within the past 3 months had poor responses to all types of vaccines. The pooled estimate for seroconversion after 1 pandemic influenza vaccine dose in these patients was 3% (95% CI, 0% to 9%). This compared poorly to both disease controls not treated with antiCD20 therapy as well as healthy controls. The risk ratio for seroconversion for those on active therapy compared to disease controls was 0.22 (95% CI, 0.09-0.56) after one vaccine dose, and 0.25 (95% CI, 0.12-1.55) after two doses. Seroconversion seems abrogated for at least 6 months following treatment. Response to vaccination improves incrementally over time but may not reach the level of healthy controls even 12 months after therapy. Safety of vaccination in this population with hematologic malignancies appeared similar to the known safety profile of the vaccines in healthy controls.
Read more: [Sosido Link] Vijenthira A, Gong I, Betschel SD, Cheung M, Hicks LK. Vaccine response following anti-CD20 therapy: a systematic review and meta-analysis of 905 patients. Blood Adv. 2021;5(12):2624-2643. doi:10.1182/bloodadvances.2021004629
Association between meconium metabolome and atopy in Canadian infants
Peterson and colleagues examined the microbiome of infant meconium to determine if there was an association with atopic disease development. Meconium, the first stool passed after birth, begins to form in the fetal gut by gestational week 16. The study obtained samples from the CHILD cohort study, which enrolled pregnant women in Vancouver, Edmonton, Winnipeg, and Toronto. Eligible infants (n = 3455) received a skin prick test (SPT) at the age of one year. Stool microbiota and the meconium metabolome were analysed in a subset of infants.
At early timepoints, infants with an atopic response at one year by SPT had a significantly less-mature microbiota than healthy non-atopic infants. Thirteen (13) of 15 taxa were decreased in relative abundance in the atopic infants compared with the controls. The differences were not persistent at one
year. The metabolites found within the meconium encapsulate a wide range of fetal exposures during gestation. Atopic infants were also found to have a significantly less metabolically rich meconium at birth compared with that of non-atopic infants, suggesting that differences may already exist at birth. Further studies may lead to a better ability to predict infants at risk of developing atopy.
Read more: [Sosido Link] Petersen C, Dai DLY, Boutin RCT, et al. A rich meconium metabolome in human infants is associated with early-life gut microbiota composition and reduced allergic sensitization. Cell Rep Med. 2021;2(5):100260. Published 2021 Apr 29. doi:10.1016/j.xcrm.2021.100260
Context for a network meta-analysis of antihistamines in chronic spontaneous urticaria
A new editorial explores the context for a network meta-analysis (NMA) of second-generation antihistamines in chronic spontaneous urticaria (CSU). The trials included in the NMA used older, less validated endpoints to measure efficacy, and did not include the globally-accepted urticaria outcomes of UAS7 and Urticaria Control Test. The trials also included varying severity of CSU, making comparisons difficult to interpret, especially in more severe patients who typically require up-dosing. Larenas-Linnemann suggests that in the future, a comparative meta-analysis evaluating both efficacy and safety of up-dosed second-generation antihistamines after more robust up-dosing trials are available.
Read more: [Sosido Link] Larenas-Linnemann D. Comparing Antihistamines in Chronic Spontaneous Urticaria: Possible Future Directions. J Allergy Clin Immunol Pract. 2021;9(6):2272-2273. doi:10.1016/ j.jaip.2021.02.024
Case series and systematic review of omalizumab for idiopathic anaphylaxis
Treatment options for idiopathic anaphylaxis (IA) without evidence of mast cell disorders are not well established. Patients typically carry epinephrine for acute episodes and are treated with antihistamines or leukotriene receptor antagonists for prevention. Kaminsky and colleagues reviewed 14 patients at two academic centres and conducted a systematic literature review to characterize the experience with omalizumab in this subset of IA patients.
The case series of patients included those with anaphylaxis-related symptoms including angioedema, urticaria, flushing, dyspnea and others. Atopic comorbidities were found in 79% of patients. Omalizumab was prescribed for CSU (93%) and asthma (7%), most often at a dose of 300mg every 4 weeks. An additional 21 patients were identified through the literature review, for a total of 35 patients. Complete responses were recorded in 63% of patients, and partial responses in 29%. Adverse events included fatigue, cough, chest tightness, flushing and edema. Included in the systematic review was a small (n = 16) double-blind placebo-controlled trial that did not demonstrate a difference in outcomes.
Read more: [Sosido Link] Kaminsky LW, Aukstuolis K, Petroni DH, Al-Shaikhly T. Use of Omalizumab for Management of Idiopathic Anaphylaxis: A Systematic Review and Retrospective Case Series [published online ahead of print, 2021 Jun 24]. Ann Allergy Asthma Immunol. 2021;S1081-1206(21)00456-7. doi:10.1016/j.anai.2021.06.017
Review on allergic rhinitis management
Linton and collaborators published a review of recent research findings in integrated care pathways, pharmacotherapy, allergen immunotherapy (AIT), biologics, probiotics, and combinations. They explore the role of telemedicine in allergy care and note that mobile health apps have begun to provide insights into patient adherence to daily therapy and symptom control. Support is provided for a multidisciplinary care model for allergic rhinitis, given the frequency of associated comorbidities and the need to integrate care between practitioners. The review provides a summary of newer pharmacologic interventions, including antihistamine-steroid nasal sprays and novel types of allergen immunotherapy such as peptide and intralymphatic delivery. The data for omalizumab and dupilumab in patients with allergic rhinitis are also summarized.
Read more: [Sosido Link] Linton S, Burrows AG, Hossenbaccus L, Ellis AK. Future of allergic rhinitis management [published online ahead of print, 2021 May 7]. Ann Allergy Asthma Immunol. 2021;S1081-1206(21)00337-9. doi:10.1016/j.anai.2021.04.029
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