Effects of allergen extract change in children receiving house dust mite immunotherapy: Real‐Life Data

were reported at a low rate in the literature. 10 All these points would be interpreted as limitations of our study. In conclusion, majority of our patients could continue their SCIT efficiently with the transition protocol developed. We hope that this protocol would be a guide in terms of providing the continuation of SCIT and increasing the compliance and success of treatment in the event that the HDM- extracts changed under real- life conditions.

Commercial firms/laboratories in Europe establish and use their own in-house reference (IHR) to standardize each allergen obtained from different sources. 2 When changing between AEs, it is important to maintain maximum therapeutic efficacy and minimize the development of potential adverse events. However, scientific evidence and the recommendations about this situation in the guidelines are limited and most of them are based on expert opinions. 3 In our country, house dust mite (HDM) extracts of two companies (Novo-Helisen Depot®, Allergopharma, Germany and Alutard-SQ®; ALK-Abelló, Netherlands) had been used in SCIT for years. During the COVID-19 pandemic, one of them could not supply the HDM-extracts due to unforeseen reasons. Therefore, manufacturer change was compulsory in patients who continued SCIT.
All patients (n = 59) who were treated with HDM SCIT for allergic rhinitis (AR) or AR with concurrent asthma during the prepandemic period (January-February 2020 for Turkey) were included in the study. Data up to September 2021 were analyzed retrospectively. In Figure 1 there is a flowchart indicating the group of patients included in our study. Patients on SCIT with HDM-extract of Alutard-SQ® were able to continue their treatment and were defined as Group 1. The other patients who were administered HDM-extract of Novo-Helisen Depot® were informed about the compulsory termination of SCIT due to the discontinuation on the Novo-Helison Depot® importation to our country. Detailed information was given to these patients and their parents about the clinical success of SCIT that had been achieved until that time, and the option of continuation to HDM SCIT with AE of the other company (ALK-Abelló, Alutard-SQ®) as well as the adverse events. In patients with established clinical efficacy and written informed consent, the SCIT was continued with HDM-extract of Alutard-SQ®. They were defined as the "transition group (TG)" and they used the transition protocol. The two different HDM-extract products had unique units as T.U./mL for Novo-Helisen Depot® and SQ/mL for Alutard-SQ®.
The transition protocol details are given in Table S1 in "Supporting Information".
Those patients who did not gave consent and could not continue SCIT were defined as Group 2. The demographic characteristics and the patients' treatment duration as well as their compliance with the treatment, adverse events, the baseline and the latest symptoms, and medication scores for AR and asthma (Table S2) were recorded.
The details are given in Supporting Information. 4,5 The study was approved by the Ethics Committee of Istanbul Medeniyet University (2021/ 0165).
While 61 LRs (8.3%) and one SR (0.13%) occurred during SCIT before transition, no SRs were recorded after transition in TG (Table S3). There were only five LRs (1.4%) observed in three patients during the induction phase. There were no adverse events     during the maintenance phase in the TG. The number of LRs per injection was significantly lower after transition than the period before transition (p = .002, Table S3).
In Group 1 and Group 2, Total Symptom Score (TSS), Total

Medication Score (TMS), Combined Symptom and MS (CSMS), and
Visual Analog Score (VAS) have improved significantly at the end of SCIT in each group of patients when compared to baseline scores (p < .001, Table S4). In addition, it is important to note that in TG, the reduction in TSS, TMS, CSMS, and VAS during the period before transition continued during the period after transition (p < .001, Table 4).
This study is one of the very few studies to demonstrate the safe and clinically effective transition to the AE produced by a different manufacturer. 6 The manufacturers use their own IHRs for standardization, and the products are assumed to have different potency and biological activity. 2,6 The results in this study showed that clinical efficacy can be maintained without any difference in the frequency of adverse events in patients undergoing HDMextract transition. Systemic reactions did not occur when HDMextract transition was done. In addition, the frequency of LR seen in patients after the transition was significantly lower than the period before the transition.
Allergen immunotherapy is effective in improving symptoms in patients with AR and has long-term efficacy after discontinuation of a regular three-year treatment course. Therefore, international guidelines do not recommend ceasing SCIT during COVID-19 pandemic. 7 Unfortunately, many studies showed a significant rate of reduction in the compliance of patients receiving immunotherapy during the pandemic, ranging from 23 to 28.7%. 8 We were able to increase the rate of continuation of SCIT from 49.1% to 79.6% by enabling 19 of 30 patients to continue treatment.
Undoubtedly, symptom and medication scores are very important in evaluating the efficacy. In a study, the adherence to SCIT with aeroallergens and the clinical outcomes of SCIT cessation during the COVID-19 pandemic were investigated. TSS, MS, and VAS were reduced significantly and the quality of life increased significantly in those who hold on treatment regularly. 9 In this study, TSS, TMS, and VAS of all groups were also reduced compared with baseline, and additionally, the improvement in TSS, TMS, and VAS of the TG proceeded.
The duration of AIT plays a role in the development of tolerance, and a reduction in the incidence of adverse events is expected during the course of AIT. However, in this study, the impact of mandatory treatment change under real-life conditions was presented retrospectively, and we did not have the chance to evaluate the specific impact of the AIT duration on transition to immunotherapy extract of another manufacturer. Additionally, one other concern would be about the use of allergoid extracts during AIT. Clinical studies have shown that allergoids are safer, more effective, and better tolerated.
Since polymerized HDM AE is not available in our country, we could not use allergoid extracts during AIT for our patients. It is important to note that some previously reported LRs were proven to be caused by the aluminum contained in the AE formulation but they TA B L E 3 Characteristics of the patients with systemic reactions during the prepandemic period. were reported at a low rate in the literature. 10 All these points would be interpreted as limitations of our study.

Gen-der
In conclusion, majority of our patients could continue their SCIT efficiently with the transition protocol developed. We hope that this protocol would be a guide in terms of providing the continuation of SCIT and increasing the compliance and success of treatment in the event that the HDM-extracts changed under real-life conditions.

FU N D I N G I N FO R M ATI O N
No funding was received for this work.

K E Y WO R DS
allergen extracts, allergen immunotherapy, child, safety, transition

CO N FLI C T O F I NTER E S T S TATEM ENT
All authors declare that they have no conflicts of interest to disclose.

Before Transition
After

S U PP O RTI N G I N FO R M ATI O N
Additional supporting information can be found online in the Supporting Information section at the end of this article.