key: cord-0903338-ab8ycxgy authors: Yeğit, Osman Ozan; Demir, Semra; Ünal, Derya; Olgaç, Müge; Terzioğlu, Kadriye; Eyice Karabacak, Deniz; Tüzer, Can; Ayhan, Vehbi; Çolakoğlu, Bahattin; Büyüköztürk, Suna; Gelincik, Aslı title: Adherence to subcutaneous immunotherapy with aeroallergens in real‐life practice during the COVID‐19 pandemic date: 2021-05-10 journal: Allergy DOI: 10.1111/all.14876 sha: 4ea97bc8bef9613417ede684bfefd38c247816e2 doc_id: 903338 cord_uid: ab8ycxgy BACKGROUND: The success of subcutaneous immunotherapy (SCIT) mostly depends on regular injections. Our aim was to investigate adherence to SCIT with aeroallergens during the COVID‐19 pandemic and demonstrate clinical consequences of treatment disruptions in real life. METHODS: Visual analogue scale for quality of life (VAS‐QoL), VAS for symptom scores (VAS‐symptom), medication scores (MSs), and total symptom scores (TSS‐6) were recorded during the pandemic in 327 adult allergic rhinitis and/or asthmatic patients receiving maintenance SCIT, and these scores were compared with the pre‐pandemic data. Patients were grouped according to SCIT administration intervals; no delay (Group 1), <2 months (Group 2), and ≥2‐month intervals (Group 3). RESULTS: A total of 104 (31.8%) patients (Group 3) were considered as nonadherent which was mostly related to receiving SCIT with HDMs and using public transportation for reaching the hospital. Median MS, VAS‐symptom, and TSS‐6 scores of Group 3 patients during the pandemic were higher than the pre‐pandemic scores (p = 0.005, p < 0.001, p < 0.001, respectively), whereas median VAS‐QoL scores of Group 3 during the pandemic were lower than the pre‐pandemic scores (p < 0.001). Median TSS‐6 and VAS‐symptom scores were the highest in Group 3 compared with other groups (p < 0.001 for each comparison). Median VAS‐QoL scores were the lowest in Group 3 compared with Group 1 and Group 2 (p < 0.001, p = 0.043, respectively). CONCLUSION: When precautions in allergy clinics are carefully applied, adherence to SCIT can be high during a pandemic. Patients must be encouraged to regularly adhere to SCIT injections since delays in SCIT administration can deteriorate clinical symptoms. AIT, the only disease-modifying therapy that confers a long-term clinical benefit for inhalant and venom allergies, has been used as a treatment modality for more than 100 years. [2] [3] [4] [5] Subcutaneous immunotherapy (SCIT), the oldest route of administration has disadvantages like necessity of regular follow-ups and applications in the clinic when compared to other routes. 2, 3, 6 Therefore, it is inevitable that there could be disruptions in SCIT administrations during the COVID-19 pandemic that has deeply affected the healthcare system. In this real-life study, the nonadherence rate of patients receiving SCIT during the COVID-19 pandemic is 31.8%. In the nonadherent patients, the use of HDM SCIT and the use of public transport for reaching the hospital are significantly higher. SCIT effectiveness and QoL levels are lower during the pandemic period than before the pandemic in the nonadherent patients. During the study period of 15 March 2020 and 15 September 2020, patients' routine SCIT injection visits were continued under strict virus transmission prevention measures. All staff members used personal protective equipments during SCIT application visits to ensure standard contact and droplet protection. 1 Wearing a surgical mask was mandatory for all patients. Sufficient time was left between each application and interviews to provide ambient ventilation, necessary preparations, and disinfection of materials that might have been contaminated. As recommended, injection visits were not interrupted unless the patient and/or his/her contact persons were infected. 1 All allergy clinics participating in the study kept providing their outpatient services in order not to affect patients' adherence during the pandemic period. Coordination between the centers was continued with regular calls during the study period to notice any failures in routine practices. Treatment interruptions and their reasons were collected through telephone interviews at the end of August 2020. In addition, the patients' educational status, professions, transportation options for reaching the hospital, smoking habits, co-morbid diseases, concomitant drug usage, and concomitant COVID-19 infection were all questioned (For detailed information, please refer to Appendix S1). The patients were allocated into three groups according to SCIT application periods. The first group consisted of the patients who Before the study, ethical approval from the ethics committee of Istanbul Faculty of Medicine (2020/78367) and authorization from The Ministry of Health for conducting the study (2020-06-04T13_52_49) were obtained. After the clinical data of each patient were filled in medical charts and were ready to be used as study documents, patients' informed consent forms were collected after the telephone interviews in order not to influence the real-life findings of the study. The patients older than 18 years of age with AR and/or allergic asthma who were receiving the maintenance phase of SCIT with pollen, house dust mite (HDM), cat, or mold allergens during the study period and those who had attended their regular SCIT application visits in the pre-pandemic period according to the medical records were included in the study. Symptom scores with both the total symptom score-6 (TSS-6) and the visual analogue scale (VAS), 8, 9 and QoL with VAS 2,9 are applied to all patients before the initiation of immunotherapy and in every 6 months until the end of the therapy as part of a routine clinical practice at the study centers. The TSS-6 was assessed by the sum of six symptoms related to nasal, ocular, ear, and/or palate with ratings for each symptom ranging from 0 to 3 with a total possible score from 0 (absence of symptoms) to 18 (very severe). 2,9 VAS-symptom scores ranged from "nasal symptoms, not at all bothersome" (0 cm) to "nasal symptoms, extremely bothersome" (10 cm). 9 The QoL scores were measured with VAS which ranged from "intolerable bothersome" (0 cm) to "not at all bothersome" (10 cm). The patients were instructed to use rescue medication as a stepwise regiment by stepping it up when symptoms were not sufficiently alleviated. The medication score (MS) from the study by Gelincik et al. was used and defined according to the steps, with a range from 0 to 6 shown in Table S1 . 2 MSs in the pre-pandemic period were determined from the data in the medical charts, whereas MSs during the pandemic were assessed at the last injection visit. A total of 327 adult patients were included in the study. The mean age was 35.0 ± 11.1 years, and a majority of them (62.4%) was female. 73.4% (n = 240), 26.3% (n = 86), and 0.3% (n = 1) of the patients had AR, concomitant AR and allergic asthma, and allergic asthma, respectively. A total of 249 (76.1%) patients were sensitive to HDM, 96 (29.3%) were sensitive to pollen, 8 (2.4%) were sensitive to cat, and 1 (0.3%) was sensitive to mold. The median duration of SCIT was 23 months (IQR 25-75: 10-36 months). During the COVID-19 pandemic, immunotherapy was administered to 151 (46.1%) patients (Group 1) at recommended intervals, 72 (22.0%) patients at extended intervals of less than 2 months (Group 2), and 104 (31.8%) patients at extended intervals of at least 2 months (Group 3). The demographic and clinical features of the patients are shown in detail in Table 1 . Univariate analysis revealed that AIT with HDM and public transport usage were higher in the nonadherent group than the adherent group (p = 0.003, p = 0.010, respectively), whereas the patients receiving pollen SCIT with or without another concomitant allergen (n = 96) were more adherent (p = 0.003) ( Table 1 ). In the logistic regression analysis, AIT with HDM and public transport usage were significantly higher among nonadherent patients (patients in Group 3) than adherent patients (patients in Group 1 and Group 2) (p = 0.009, p = 0.026, respectively) ( Table 2) . When categorizing the patients according to their duration of maintenance phases as those in the 1st, 2nd, or the 3rd year, we could not show any significance among adherent and nonadherent groups. Before the pandemic, the median TSS-6, VAS-symptom, MS, and VAS-QoL scores were similar in all groups (p > 0.05 for each comparison). During the pandemic, the median TSS-6 and VAS-symptom scores were the highest in Group 3 compared with other groups (p < 0.001 for each comparison) and these values were similar between Group 1 and Group 2 (p > 0.05, p > 0.05, respectively). The median MSs were similar in all groups during the pandemic (p > 0.05). Median VAS-QoL scores were the lowest in Group 3 compared with others (p < 0.001 for each comparison) and were lower in Group 2 than Group 1 (p = 0.043) (Figure 1 ). When comparing adherent and nonadherent patients, the median TSS-6, VAS-symptom, MS, and VAS-QoL scores were similar before the pandemic (p > 0.05 for each comparison). During the pandemic, the median TSS-6 and VAS-symptom scores were higher and the median VAS-QoL score was lower in the nonadherent patients than the adherent patients (p < 0.001 for each comparison). However, the median MS was similar in both groups during the pandemic (p > 0.05) (Figure 2 ). Since the study period corresponds to the pollination period of common pollen allergens in our geographic region, the patients who received and those who did not receive pollen immunotherapy were compared in terms of short-term clinical outcomes of AIT. Changes in MS, VAS-symptom, VAS-QoL, and TSS-6 scores between the pandemic and the pre-pandemic periods were similar among these patients (p > 0.05 for each comparison). Comparison of ACT scores between and within the groups during the pandemic and pre-pandemic periods was similar (p > 0.05 for each comparison). Firstly, the changes in MS, VAS-symptom, VAS-QoL, and TSS-6 scores between the pandemic and pre-pandemic periods were calculated. Then, the increased SCIT application intervals were assessed separately with the changes in these four scores with the correlation analysis. A moderate correlation between the increase in the interval of SCIT application and the differences in VAS-symptom (r = .509, p < 0.001), VAS-QoL (r = .516, p < 0.001), and TSS-6 (r = .521, p < 0.001) scores was observed. The difference in MSs between pre-pandemic and during the pandemic periods showed a very weak correlation (r = .188, p < 0.001) (Figure 3 ). During the study period, 12 patients were diagnosed with COVID-19. The mean age of the patients was 37.5 ± 11.5, and 7 (58.3%) of them Our study is the first multicenter study which has evaluated adherence to SCIT with aeroallergens during the COVID-19 pandemic and its influence on the short-term clinical outcomes in real-life. We observed that in half of the patients (53.8%), SCIT injections were delayed and one third (31.8%) of the patients were nonadherent during COVID-19 pandemic. Delays in SCIT administration have led to deterioration in the AIT effectiveness and QoL, and the deterioration was even greater in the nonadherent patients. Adherence to long-term treatments in chronic diseases is very crucial for the success of the treatment. 3 The definition of adherence to SCIT differs in studies; however, we referred to a previous study which was conducted by our group and considered the cutoff time interval for being nonadherent as 2 months accordingly. 2 Moreover, we also determined the clinical results of shorter delays of less than 2 months in injection intervals in a separate patient group in order to strengthen our findings. By this way, we have captured all significant clinical consequences of delays in injection intervals. Since our study is Note: Group 1 = routine intervals; Group 2 = extended intervals (<2 months); Group 3 = extended intervals(≥2 months); NS = nonsignificant; HDM = house dust mite. * The p-value was calculated between adherent and nonadherent groups. Statistical significance level was set at < .05 and value of statistical significance was marked in bold. the first adherence study during the pandemic, we could only compare our results with previous SCIT adherence studies published before the pandemic. In the majority of the adherence studies on SCIT, the adherence rates are less than 70.0%. 2,10-13 Furthermore, they are even lower according to real-life data. 2, 14, 15 In our study, 68.2% of the patients were adherent to SCIT during the pandemic. We can speculate that this acceptable adherence rate in our study may be due to continuous treatment with appropriate preventive measures applied and the close cooperation that had been established between the allergists and the patients in the study centers before the pandemic despite the negative effects of the pandemic. In the centers of the study, in order to provide the close cooperation, the same allergy specialists observed the patients before and 30 min after each shot and the same allergy nurses applied the injections throughout the therapy. In every visit, the physicians evaluated the improvement of the clinical conditions, gave detailed information to the patients and specified the next injection appointment. As the clinical practice in SCIT visits has not changed during the pandemic, we believe the adherence rate observed during the study period reflects the influence of the pandemic on SCIT adherence in our patients. As a main finding of our study, delay in SCIT administrations led to deterioration in AR symptoms and QoL of our patients. Delays of less than 2 months between subsequent SCIT injections worsened QoL and symptom scores in Group 2 patients, whereas in the nonadherent group MSs were additionally disrupted. This disruption is due to the fact that anti-allergic medication was needed to relieve their symptoms. Therefore, we suggest that it is important to continue SCIT injections without extending intervals more than recommended in order not to affect the short-term effectiveness of AIT even during a pandemic. 16 Prolonged intervals in the SCIT applications are also an important issue to make appropriate dose adjustments to restart SCIT after gaps in the administration. 17 In our study, after interruptions of maintenance doses especially in nonadherent patients, dose adjustments starting with frequent lower dose injections caused frequent hospital visits which can probably bring additional burden on the healthcare system. The two main reasons of nonadherence to SCIT in our study were using public transport for reaching the hospital and receiving SCIT with HDMs. In accordance with our findings, a study from the USA reported that one of the reasons of premature cessation of SCIT was the inconvenience of travel. 18 Our study focused on only the effects of patient behaviors on SCIT application during the pandemic, since none of the SCIT application intervals was changed by a physician's approaching the study. Authors state that there is no conflict of interest about this study. 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