key: cord-0980701-7odablpv
authors: Bragança, Mariana; Plácido, José Luís; Amaral, Luís
title: Ultra-rush immunotherapy with polymerized extracts during COVID-19 pandemic: safety of restarting administrations without dose-adjustments
date: 2022-02-25
journal: Ann Allergy Asthma Immunol
DOI: 10.1016/j.anai.2022.02.014
sha: e45e7c1b00ef14de297cd43049f2583772209d07
doc_id: 980701
cord_uid: 7odablpv

nan

Allergen-specific immunotherapy (AIT) is the only therapy that can change the natural history of allergic diseases and it has been established as an effective treatment in immediate-type allergic reactions and associated diseases such as asthma and rhinoconjunctivitis. This applies to both subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT).

SCIT is safe and mostly well tolerated. However, patients are required to attend a medical facility with trained staff and proper equipment to manage potential reactions. 1 In our department nearly 4500 SCIT injections are carried out annually.

Polymerized extracts are used in more than 99% of our patients. These extracts result from polymerization of allergens into high molecular weight molecules using glutaraldehyde as a cross-linking agent, reducing allergenicity while retaining immunogenicity. Differences from unmodified extracts are shown in table 1. 2 An ultra-rush protocol is routinely used in the build-up phase of SCIT which consists of the administration of 0.2-and 0.3-ml doses in alternate arms with a 30-minute interval reaching the maintenance dose of 0.5 ml on the first day. Thereafter, this dose is administered monthly. In our experience, this is an effective, practical and safe schedule to follow. Previous studies using ultra-rush AIT with polymerized extracts described local and mild systemic reactions in 11% and 1% of patients, respectively. 3, 4 The SARS-CoV-2 pandemic had a significant impact in our clinical practice. In Portugal, the national state of emergency was declared and lockdown measures were imposed in March 2020, soon after the World Health Organization (WHO) declared COVID-19 as a pandemic. As a result, our regular clinical activity was suspended until May. Patients in maintenance phase of aeroallergens SCIT were encouraged to keep the scheduled doses at their primary care facilities. However, due to an overload of COVID-19 related tasks, a significant percentage of patients were forced to delay SCIT administration. 5 With the reestablishment of regular clinical activity after the lockdown, these patients were invited to resume their treatments without dose adjustment, after a three-month interruption. The rationale was to reduce the time of surveillance after injections in order to avoid overcrowding the waiting room during a pandemic phase, as government restrictions were still in place to limit patient flow in health care facilities. This also allowed for a higher number of SCIT restarts per day.

A retrospective analysis of demographic and clinical data of patients receiving maintenance SCIT with aeroallergens, who missed doses due to COVID-19 restrictions and restarted their treatment at our center between May and July 2020, was performed to assess the safety of reinitiating aeroallergen SCIT without dose adjustments. Patients with systemic reactions in previous administrations were not included in this analysis. They were submitted to an ultra-rush protocol. The adverse reactions reported were classified as local reaction, local large reaction (defined as pruritus and/or erythema >2.5 cm at the site of injection) and systemic reactions. 6 A total of 273 patients were scheduled, but only 241 restarted SCIT. The mean age (SD) was 23 ± 14 years and 53.5% were male. The diagnosis of allergic rhinitis was present in 97.5% patients, of which 45.1% and 12.9% had concomitant conjunctivitis and atopic dermatitis, respectively. Asthma was present in 36.8% of patients. Most patients were polysensitized (66%) with a mean of 3.6 ± 1.9 positive allergens per patient. All patients were under SCIT with polymerized aeroallergen extracts, 51.0% to house dust mite (HDM) and 58.1% of these with more than one allergen, 24.1% to pollens and of these 26.2% also with more than one; 24.1% to a mix of HDM and pollens, and 0.8% to a mix of HDM and cat. The mean number of days overdue was 65 ± 14 days, ranging from 23 to 146 days, and the mean duration of treatment before the missed dose was 98.9 ± 4.4 weeks. To be effective, SCIT should be continued for at least three years, requiring regular visits to a health care facility, as systemic reactions may occur. 6 In early 2020, due to the COVID-19 pandemic, clinical practice adjustments were made in many Allergy Departments because most health care staff were redirected to COVID-19 related activities, or even to ensure the safety of both patients and health care workers. Additionally, patient adherence to SCIT decreased due to caution and fears of public spaces and hospitals. 7 As a result, many patients interrupted their aeroallergen SCIT or increased the administration intervals with a potential decline in efficacy. 8 Therefore, whenever possible, treatment was restarted taking into consideration the riskbenefit analysis. 9 Scientific literature is scarce and divergent regarding restarting SCIT after missed doses. Safety is a major concern when patients have gaps in immunotherapy administration, and most adjust the dose according to the time interval since the last injection. Protocols from several centers were analyzed and in cases of > 35 days since last dose (i.e., > 7 days overdue), the dose was reduced. 8 Data from our center suggests that restarting SCIT with polymerized aeroallergen extracts in patients in maintenance phase without previous systemic reactions is safe without the need for dose adjustment, including a wide interval, to a maximum of 146 days.

It is noteworthy that none of the patients treated with SCIT for pollens had adverse reactions during the pollen season, questioning the necessity for seasonal dose adjustment. However, the restarts were done between May and July, and all adult and adolescent patients were compelled to use face mask, including outdoors during this period, which limits contact with pollen allergens.

In conclusion, there is no standard adjustment protocol for missed doses during aeroallergen SCIT, and most allergists adjust doses according to the time interval since the last injection. Our results suggest that is safe to restart SCIT with polymerized aeroallergen extracts during maintenance phase without the need for dose adjustment in those without a previous systemic reaction.

Randomized clinical trials and other prospective data are needed to support this hypothesis, as this is an empiric observation with modified extracts from a single center.

Allergic Rhinitis and its Impact on Asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen)

Modified forms of allergen immunotherapy

Ultrarush schedule of subcutaneous immunotherapy with modified allergen extracts is safe in paediatric age

Characterisation of systemic reactions to subcutaneous immunotherapy with airborne allergens and classification according to WAO 2010

Real-life experience of an allergy and clinical immunology department in a Portuguese reference COVID-19 hospital

Allergen immunotherapy: an updated review of safety

Adherence to subcutaneous immunotherapy with aeroallergens in real-life practice during the COVID-19 pandemic

Gaps in allergen immunotherapy administration and subcutaneous allergen immunotherapy dose adjustment schedules: Need for prospective data

Allergen immunotherapy in the current COVID-19 pandemic: A position paper of

German Society for Applied Allergology (AEDA)(D), German Society for Allergology and Clinical Immunology (DGAKI)(E), Society for Pediatric Allergology (GPA)(F) in cooperation with AG Clinical Immunology, Allergology and Environmental Medicine of the DGHNO-KHC(G) and the European Academy of Allergy and Clinical Immunology (EAACI)(H)