key: cord-0719905-za745vv5
authors: Larenas-Linnemann, Désirée; Epstein, Tolly; Ponda, Punita; Bernstein, David; Williams, Paul; Creticos, Peter
title: Gaps in allergen immunotherapy administration and SCIT dose-adjustment schedules: need for prospective data
date: 2020-07-18
journal: Ann Allergy Asthma Immunol
DOI: 10.1016/j.anai.2020.07.015
sha: 5ab4c71f6997d85117b7d0071353506172554516
doc_id: 719905
cord_uid: za745vv5

nan

Introduction (1006 words) 1 Many abrupt adjustments in the delivery of medical care became necessary due to the 2 unexpected emergence of the COVID-19 pandemic in early 2020. In order to ensure social 3 distancing and the concomitant requirements for personal protective equipment, practitioners 4 have had to make a myriad of adjustments in order to continue providing subcutaneous allergen 5 immunotherapy (SCIT). In many practices SCIT was stopped or administration intervals have 6 been increased, while other practices have transitioned some patients to the sublingual 7 administration route.(1) 8 9 Although many locations have recently eased 'lockdown' requirements, in several states this led 10 to a rise in cases, resulting in further 'lockdowns'. Thus it might very well still take months 11 before our daily routine shall come close to normal again. Learning from historical lessons, the 12 H1N1-influenza 'Spanish Flu' pandemic lasted fifteen months and killed 50 million people. It 13 comprised three waves: the first (milder) one was in winter-spring 1918; the second wave, in 14 September 1918, was disastrous and deadly, as it coincided with the massive troop gathering and 15 transport of soldiers for World War I and an apparent aggressive mutation of the virus; and the 16 last wave, beginning in 1919, had less severity. Finally, the virus resolved upon the development 17 of herd immunity, the ending of war, and possibly a favorable mutation. 18

While prevention of infection with SARS-CoV-2 is critical, it is also important that other health 20 concerns are addressed, to limit preventable emergencies. And, maintaining good health appears 21 to reduce the risk of severe COVID-19 disease. In the context of allergic diseases, SCIT has been 22 demonstrated to reduce symptoms and medication requirements in allergic rhinitis, conjunctivitis 23 and in patients with IgE-dependent asthma, as well as improve quality of life. Moreover, a case 24 could be made that allergic patients might experience some ancillary immunologic benefit in 25 battling an infectious pathogen, by being on an effective SCIT dose. Immunotherapy restores the 26 function of dendritic cells and augments the number of active type 1 helper T cells; both enhance 27 innate immunity which could be important at the start of a SARS-COV-2 infection, with initial 28 innate immune suppression by the virus; a theory that might be interesting to explore.(2) 29 30 For SCIT to be effective, an optimal target monthly maintenance dose has to be administered. 31

The extended spacing interval of injections, although acceptable from a safety point of view, 32 may result in a diminution of therapeutic efficacy. Thus, as soon as the risk for SARS-CoV-2 33 transmission and infection can be reduced to levels considered safe by health authorities, it 34 behooves the allergist to return to a maintenance immunotherapy schedule known to be effective. Tangentially, the focused practice parameter update on sublingual immunotherapy recommends 48 re-starting tablet SLIT in-office after interruptions of more than seven days. This is 49 recommendable as anaphylaxis has been reported after the first tablet. There is no consensus or firm evidence suggesting which dose adjustment strategy is superior 84 after a gap in therapy. In addition, it is unclear whether some patients may tolerate longer gaps in 85 therapy than previously allowed, both in terms of efficacy and safety. Understanding the 86 consequences and developing optimal strategies for dose adjustment after gaps in therapy has 87 become paramount during the COVID-19 pandemic. Thus, the AAAAI Immunotherapy, 88

Allergen Standardization and Allergy Diagnostics Committee is evaluating outcomes related to 89 various dose adjustment strategies for gaps in therapy. A prospective, randomized single-center 90 trial evaluating outcomes for two different dose-adjustment schedules is underway. In addition, 91

we are gathering data using the Immunotherapy Surveillance Study. We would like to invite 92 colleagues to join us and submit their data regarding gaps in therapy to the Surveillance study: 93 www.surveillancestudysubscription.com 94

The below tables are some examples of different schedules for dose-adjustment after gaps in SCIT administration, developed by academia, large practices and guidelines in an attempt to minimize the possibility of a systemic reaction. However, avoidance of a reaction cannot be guaranteed. The physician is further guided in the exact dose adjustment decision by clinical data such as the concentration of allergen being given, previous reaction history, seasonality, etc. ETable 1.

All patients Intuitively, highly sensitive patients* might need special caution and more drastic dose reduction after gaps Restart SCIT: from bottle 1, 1 st dose * Special caution might be needed for 1) History of anaphylaxis or mast cell disorder; 2) Moderate-to-severe asthma; 3) High sensitization pattern or systemic reaction during skin prick testing; 4) Systemic reactions to previous SCIT administration; 5) Patients receiving SCIT during peak pollen season for an allergen to which they are highly sensitized; 6) Pediatric patients. 

COVID-19's impact on allergists' clinical services and protocols 2020

Mexican Immunotherapy Working G. COVID-19 and allergen immunotherapy: theoretical benefits invite to adjustments in practice recommendations

Acute systemic reactions to sublingual immunotherapy for house dust mite

Survey on immunotherapy practice patterns: dose, dose adjustments, and duration

AAAAI/ACAAI Subcutaneous Immunotherapy Surveillance Study (2013-2017): Fatalities, Infections, Delayed Reactions, and Use of Epinephrine Autoinjectors. The journal of allergy and clinical immunology In practice

For lapses in therapy in the 1:10,000, 1:1,000, and 1:100 vials, adjust dose as follows: 

Modify dosage accordingly to time interval since missed injection Up to 7 days* Continue as scheduled 8-13 days after missed scheduled injection Repeat previous dose** 14-21 days after missed scheduled injection reduce dose 25%** 21-28 days after missed scheduled injection Reduce previous dose 50%** 'A similar dose-reduction protocol should be developed for gaps in maintenance immunotherapy' * i.e., if on weekly build-up, then it would be up to 14 days after administered injection or 7 days after the missed scheduled injection) ** Then increase dose each injection visit as directed on the immunotherapy schedule until therapeutic maintenance dose is reached ETable 7 Dose-adjustment schedule Mexican guidelines on immunotherapy 2019