Discussion
Results of our study showed that the overall compliance rate among patients receiving AIT was 86,1% and short duration of AIT and receiving venom or asthma immunotherapy were found to be associated with non-compliance. In addition, the most common reasons for drop-out were moving to another city, improvement of symptoms and ineffectiveness. However, nearly one-third of children dropped out during the COVID-19 pandemic, and fear of being infected with COVID-19 was the most common reason.
Compliance rates for SCIT range from 44% to 89%, in the present study compliance found to be better than other studies3. Similar to our results, Pajno et all found that AIT compliance of children on SCIT was 89%4. In a population of 311 allergic adult and child patients receiving dust mite SCIT in China, 34,5% of caseswere noncompliant and ineffectiveness(28%) was the leading reason for drop-out15. The cost of AIT in our country is under the umbrella of social security system. This may be a major reason for high compliance rates we achieved. Additionally our staff reminds the patients if a patient does not come to a regular visit (except COVID-19 period).
We concluded that drop-out was significiantly higher in patients who receiving immunotherapy for asthma and venom allergy. As the patients who received VIT admitted from another city, most of them dropped out due to the long distance or frequency of injections. However in previous studies, the association of kind of respiratory allergic diseases and adherence were inconsistent. In one study, allergic conjunctivitis were found associated with non-adherence whereas in other study patients with asthma and rhinitis were found more adherent16,17. More et all reported that the kind of respiratory allergic diseases was not correlated with adherence18.
In the current literature the data about the AIT compliance were mostly attained from studies in adults, and there are few data related to SCIT adherence in children. The studies comparing different age groups with respect to the AIT compliance give us conflicting results19,20. Yang et all found that children had higher adherence than adults15. Lee et al concluded that patients aged <20 years and 20-40 years were more likely to be nonadherent than those aged >40 years. Rhodes found, nonadherent patients were younger21.
In the present study, gender did not influence the adherence rate before pandemic. However during the COVID-19 pandemic period males droped out more significantly. Musa, Rhodes and Gelincik found no correlation with gender5,20,21. Rhodes found, males were more nonadherent21. However in Yang’ and Lower’s study males had higher adherence2,15.
Our results suggested that moving to another city (32,9%) was the main cause of drop-outs. Due to the lack of allergologists in some cities, treatment could not be resumed. In addition, all of the patients receiving AIT were at school age, and increased injection frequency, transportation to different city and long distances probably caused school absences and AIT drop-out.
Improvement of symptoms was the second leading reason of drop out (17,9%). Lourenco reported that the frequency of drop-out because of clinical improvement was 23% and mostly during the second and third year of SCIT19. Yang reported it as 22%15.
We found treatment ineffectiveness (14,3%) as another important reason of AIT drop-outs. Ineffectiveness was reported in previous studies in 8 to 66% of drop-out results1,4,15,19,20. Adverse reactions were also reported in several studies as a reason for drop-outs in 3,9% to -11% of drop-outs19,21. Systemic reactions were also one of the leading reasons for drop-out (14,3%) in the present study although it was not reported frequently in our center previously22,23(24). In contrast to literature, cost was not a reason for drop-out in the present study as AIT treatment is covered by social security system of our country.
During the COVID-19 pandemic period, in allergy department, patient admissions were stopped except for emergency situations and immunotherapy vaccination. Even so, among the 108 patients receiving AIT, 31 (28,7%) dropped out. Fear of being infected with COVID-19 was the most reason. Although the necessary precautions were taken, the patients chose not to continue to AIT, as the hospital was a COVID-19 pandemic center. Twenty nine percent of patients dropped out thinking that the AIT was cancelled because of the news on the press that the admissions of patients stopped except for emergencies. In COVID-19 pandemic period, intercity transportation was banned and, in most of the cities including Ankara curfews were declared. This situation resulted in 22,7% of patients’s drop-out due to transportation problems. Six and a half percent of patients could not get access to allergen extract. One patient was unable to continue AIT, as his father, a health worker, was hospitalized because of COVID-19 pneumonia. One patient’s AIT was terminated earlier, who was an out of town patient and in the final months of AIT.
Older age and male gender were correlated with drop-out during the COVID-19 pandemic. Closure of schools and home-quarantine during pandemic was reported to cause anxiety in adolescents24. Older adolescens may have taken the treatment responsibility themselves and tended to refuse outpatient admission. Besides, male sex was reported as a risk factor for COVID-19 severity25. These might be associated with reduced outpatient admissions.
Longer AIT duration, was found to be associated with drop-out during the COVID-19 pandemic period. We may speculate that the effectiveness of the AIT up to this period, might cause noncompliance.
Although our study brings some new data to the field there are some limitation. Firstly, this is a retrospective study up to the COVID-19 pandemic period, and there are some missing data related laboratory parameters. Secondly, in the present study, definition of compliance differs from in many studies and may lead to difficulty in comparing factors associated with AIT compliance. Thirdly, some of the patient’s immunotherapy is stilll ongoing. Therefore the compliance rate may be higher than other studies for this reason. Despite this limitations, the present study had the benefits of a large study population including only children and analyzes the effect of COVID-19 pandemic on AIT for the first time.